Vagifem 25 ?g film-coated tablets


Vagifem 25 micrograms film-coated vaginal tablets

Estradiol hemihydrate

Read all of this leaflet carefully, before you start using this medicine. Keep this leaflet. You may need to read it again. If you have any questions, ask your doctor or pharmacist. This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours. If any of the side effects get serious, or if you notice any side effects not listed in this leaflet please tell your doctor or pharmacist. In this leaflet: 1. What Vagifem is and what it is used for 2. Before you use Vagifem 3. How to use Vagifem 4. Possible side effects 5. How to store Vagifem 6. Further information What Vagifem Is And What It Is Used For

Vagifem contains estradiol

Estradiol is a female sex hormone It belongs to a group of hormones called oestrogens It is exactly the same as the estradiol produced by the ovaries of women.

Vagifem belongs to a group of medicines called Hormone Replacement Therapy (HRT).

It is intended for post-menopausal women and is used to relieve menopausal symptoms in the vagina such as dryness or irritation. In medical terms this is known as ‘vaginal atrophy’. It is caused by a drop in the levels of oestrogen in your body. This happens naturally around the menopause.

Vagifem works by replacing the oestrogen which is normally produced in the ovaries of women.

It is inserted into your vagina, so the hormone is released where it is needed.

The experience of treating women older than 65 years is limited.

Before You Use Vagifem Medical check-ups

Before you start using Vagifem, your doctor will tell you about the risks and benefits of the treatment (see also Section 4). Before you start using Vagifem and regularly during treatment, your doctor will check whether Vagifem is the right treatment for you. Once you’ve started on HRT, your doctor will tell you how often to go for regular check-ups. At these check-ups, your doctor may discuss with you the benefits and risks of continuing to take HRT.

If you have a close relative (e.g. mother, sister, maternal or paternal grandmother), who has suffered from any serious illness such as blood clots or breast cancer, you might be at a higher risk for serious illness. Always tell your doctor about any close relative(s) suffering from serious illness.

As well as regular check-ups with your doctor, you should:

Regularly examine your breasts for any changes, such as dimpling or sinking of the skin, changes in the nipple, or any lumps you can see or feel. Tell your doctor if you notice any changes. Go for regular breast screening (mammography) and cervical smear tests. Do not use Vagifem if: You are allergic (hypersensitive) to estradiol or any of the other ingredients of Vagifem (listed in Section 6 below) You have or have ever had, or think you might have breast cancer You have or have had a hormone dependent tumour (e.g. cancer of the lining of the womb) You have unusual vaginal bleeding which you have not told your doctor about You have thickening of the lining of the womb (endometrial hyperplasia) and you are not being treated for it You have or previously have had a blood clot inside the blood vessels of the legs or lungs (deep vein thrombosis or pulmonary embolism) You have porphyria. This is a rare disease which affects the production of some of your blood pigments. You have active or recent arterial thromboembolic disease (e.g. angina, myocardial infarction) You have acute liver disease or history of liver disease as long as liver function tests have failed to return to normal

Do not use Vagifem if any of the above applies to you. If you are not sure, talk to your doctor or pharmacist before using this medicine.

Take special care with Vagifem

Check with your doctor before using Vagifem if you have or have ever had any of the illnesses in the list below. He or she may want to follow you more closely.

Asthma Epilepsy Diabetes Gallstones High blood pressure Migraines or severe headaches Liver problems such as ‘liver adenoma’ (a benign tumour) Endometrial hyperplasia (thickening of the lining of your womb) Otosclerosis. This is when you lose your hearing over a period of time Systemic lupus erythematosus (a disease affecting the skin, joints and kidneys) Blood clots or risk factors for blood clots (see Section 4 ‘Other side effects of systemic HRT’) Leiomyoma (benign tumours of the womb) or endometriosis (growth of the womb lining outside the womb)

If any of the above applies to you, or if you are not sure, talk to your doctor or pharmacist before using Vagifem.

Using other medicines

Please tell your doctor or pharmacist if you are using or have recently used any other medicines, including medicines obtained without a prescription.

Pregnancy and breast-feeding Do not use Vagifem if you think you might be pregnant, or if you are breast-feeding If you get pregnant while you are using Vagifem, stop using it and see a doctor straight away. Driving and using machines

No known effect.

How To Use Vagifem

Always use Vagifem exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.

Using this medicine You can start using Vagifem on any day which is best for you Insert the vaginal tablet into your vagina with the applicator.

The ’USER INSTRUCTIONS’ at the end of the leaflet tell you how to do this. Read the instructions carefully before using Vagifem.

How much to use Use one vaginal tablet each day for the first 2 weeks Then use one vaginal tablet twice a week. Leave 3 or 4 days between each dose. If you use more Vagifem than you should If you have used more Vagifem than you should, talk to a doctor or pharmacist. An overdose of oestrogen could make you feel sick or vomit. If you forget to use Vagifem If you forget a dose, use the medicine as soon as you remember. Do not use a double dose to make up for a forgotten dose.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

General information about treating symptoms of the menopause When using medicines for any menopausal symptoms, use the lowest dose that works. Also, use the medicine for as short a time as you need to.

Only continue treatment if the benefit is more than the risk.

Talk to your doctor about this.

Possible Side Effects

Like all medicines, Vagifem can cause side effects, although not everybody gets them.

Stop using Vagifem and see a doctor straight away if you notice any of the following side effects: A migraine-type headache you have not had before Yellow colouring of your skin or eyes (jaundice) or other liver problems A big increase in blood pressure Blood clots called ‘deep vein thrombosis’ (see also ‘Other side effects of systemic HRT’) If you develop any of the illnesses listed in Section 2, ’Do not use Vagifem’ You become pregnant Tell your doctor or pharmacist if any of the following side effects get serious or last longer than a few days:

Common (may affect more than 1 in 100 women)

Headache Passing wind (flatulence) Feeling sick (nausea) or being sick (vomiting) Indigestion Stomach pain, discomfort or distension Swelling of arms or legs (oedema) Vaginal bleeding, discharge or discomfort An infection of the genitals caused by a fungus or inflamed vagina Breast oedema or breast enlargement, breast pain or breast tenderness.

Very rare (may affect less than 1 in 10000 women)

Breast cancer Cancer of the lining of the womb (endometrial cancer) Thickening of the lining of your womb (endometrial hyperplasia) Blood clots called ‘deep vein thrombosis’ Other side effects of systemic HRT are: Allergic reaction (hypersensitivity) Diarrhoea Weight increase Fluid retention Being unable to sleep (insomnia) Feeling depressed Worsening of existing migraine Rash, including itchy, lumpy rash called ‘hives or urticaria’ Itching of the genitals Vaginal pain, irritation of the vagina, painful spasm of the vagina (vaginismus) or vaginal ulcers Increase in blood oestrogen (shown in blood test) Drug ineffective. Important information on the side effects of HRT

Vagifem is used for local treatment in the vagina and contains only a small amount of estradiol. This means that the chances of getting the diseases described below are less likely than with HRT products used for systemic treatment (treatment that affects the body as a whole).

As well as benefits, HRT has some risks which you need to consider when you’re deciding whether to take it, or whether to carry on taking it.

Effects on your heart or circulation

Heart disease

HRT is not recommended for women who have heart disease, or have had heart disease recently. If you have ever had heart disease, talk to your doctor to see if you should be taking HRT. HRT will not help to prevent heart disease.

Studies with one type of HRT (containing conjugated oestrogen plus the progestogen MPA) have shown that women may be slightly more likely to get heart disease during the first year of taking the medication. For other types of HRT, the risk is likely to be similar, although this is not yet certain.

If you get:

a pain in your chest that spreads to your arm or neck See a doctor as soon as possible and do not take any more HRT until your doctor says you can. This pain could be a sign of heart disease.

Stroke

Recent research suggests that systemic HRT slightly increases the risk of having a stroke. Other things that can increase the risk of stroke include:

getting older high blood pressure smoking drinking too much alcohol an irregular heartbeat

If you are worried about any of these things, or if you have had a stroke in the past, talk to your doctor to see if you should take HRT.

Compare

Looking at women in their 50s who are not taking HRT - on average, over a 5-year period, 3 in 1000 would be expected to have a stroke.

For women in their 50s who are taking HRT, the figure would be 4 in 1000.

Looking at women in their 60s who are not taking HRT - on average, over a 5-year period, 11 in 1000 would be expected to have a stroke.

For women in their 60s who are taking HRT, the figure would be 15 in 1000.

If you get:

unexplained migraine-type headaches, with or without disturbed vision See a doctor as soon as possible and do not take any more HRT until your doctor says you can. These headaches may be an early warning sign of a stroke.

Blood clots

Systemic HRT may increase the risk of blood clots in the veins (also called deep vein thrombosis, or DVT), especially during the first year of taking it.

These blood clots are not always serious, but if one travels to the lungs, it can cause chest pain, breathlessness, collapse or even death. This condition is called pulmonary embolism, or PE. DVT and PE are examples of a condition called venous thromboembolism, or VTE.

You are more likely to get a blood clot:

if you are seriously overweight if you have had a blood clot before if any of your close family have had blood clots if you have had one or more miscarriages if you have any blood clotting problem that needs treatment with a medicine such as warfarin if you’re off your feet for a long time because of major surgery, injury or illness if you have a rare condition called SLE

If any of these things apply to you, talk to your doctor to see if you should take HRT.

Compare

Looking at women in their 50s who are not taking HRT - on average, over a 5-year period, 3 in 1000 would be expected to get a blood clot.

For women in their 50s who are taking HRT, the figure would be 7 in 1000.

Looking at women in their 60s who are not taking HRT - on average, over a 5-year period, 8 in 1000 would be expected to get a blood clot.

For women in their 60s who are taking HRT, the figure would be 17 in 1000.

If you get:

painful swelling in your leg sudden chest pain difficulty breathing See a doctor as soon as possible and do not take any more HRT until your doctor says you can. These may be signs of a blood clot.

If you’re going to have surgery, make sure your doctor knows about it. You may need to stop taking HRT about 4 to 6 weeks before the operation, to reduce the risk of a blood clot. Your doctor will tell you when you can start taking HRT again.

Effects on your risk of developing cancer

Breast cancer

Women who have breast cancer, or have had breast cancer in the past, should not take HRT

Taking HRT slightly increases the risk of breast cancer; so does having a later menopause. The risk for a post-menopausal woman taking oestrogen-only HRT for 5 years is about the same as for a woman of the same age who’s still having periods over that time and not taking HRT.

The extra risk of breast cancer goes up the longer you take it, but returns to normal within about 5 years after stopping HRT.

Your risk of breast cancer is also higher:

if you have a close relative (mother, sister or grandmother) who has had breast cancer if you are seriously overweight

Compare

Looking at women aged 50 who are not taking HRT - on average, 32 in 1000 will be diagnosed with breast cancer by the time they reach the age of 65.

For women who start taking oestrogen-only HRT at age 50 and take it for 5 years, the figure will be between 33 and 34 in 1000 (i.e. an extra 1-2 cases).

If they take oestrogen-only HRT for 10 years, the figure will be 37 in 1000 (i.e. an extra 5 cases).

If you notice

any changes in your breast, such as:

dimpling of the skin changes in the nipple any lumps you can see or feel Make an appointment to see your doctor as soon as possible.

Endometrial cancer (cancer of the lining of the womb)

Taking oestrogen-only HRT tablets orally for a long time can increase the risk of developing cancer of the lining of the womb (the endometrium). It is possible there may be a similar risk with oestrogen cream/rings/tablets used directly in the vagina for repeated treatments or over a long time.

If you get breakthrough bleeding or spotting, it’s usually nothing to worry about, but you should

Make an appointment to see your doctor. It could be a sign that your endometrium has become thicker.

Ovarian cancer

Ovarian cancer (cancer of the ovaries) is very rare, but it is serious. It can be difficult to diagnose, because there are often no obvious signs of the disease.

Some studies have indicated that taking oestrogen-only HRT for more than 5 years may increase the risk of ovarian cancer. It is not yet known whether other kinds of HRT increase the risk in the same way.

HOW TO STORE Vagifem

Keep out of the reach and sight of children.

Do not store above 25°C. Do not refrigerate. Keep the blisters in the outer carton in order to protect from light.

Do not use Vagifem after the expiry date which is stated on the carton. The expiry date refers to the last day of that month.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

Further Information What Vagifem contains The active substance is estradiol 25 micrograms (as estradiol hemihydrate) Other ingredients are: hypromellose, lactose monohydrate, maize starch and magnesium stearate The film-coating contains: hypromellose and Macrogol 6000. What Vagifem looks like and content of the pack

Each Vagifem comes in an applicator which is used once only.

There are 15 applicators with vaginal tablets in each box.

Vagifem is engraved with NOVO 279.

Marketing Authorisation Holder Novo Nordisk A/S Novo Alle DK-2880 Bagsvaerd Denmark The registered office in the UK is: Novo Nordisk Limited Broadfield Park Crawley West Sussex RH11 9RT Tel:(01293) 613555

This leaflet was last approved in: 04/2010

Detailed information on this medicine is available on the web site of www.emc.medicines.org.uk

User Instructions How to use Vagifem 1. Tear off one single blister pack. Open the end as shown in the picture. 2. Insert the applicator carefully into the vagina.

Stop when you can feel some resistance.

3. To release the tablet, gently press the push button until you feel a click.

The tablet will stick to the wall of the vagina straight away.

It will not fall out if you stand up or walk.

4. Take out the applicator and throw it away

Vagifem is a trademark owned by Novo Nordisk Femcare AG, Switzerland.

© 2010

Novo Nordisk A/S

8-2790-01-033-1


read more


Salazopyrin Suppositories


1. Name Of The Medicinal Product

Salazopyrin Suppositories

2. Qualitative And Quantitative Composition

Sulfasalazine EP 0.5 g

3. Pharmaceutical Form

Suppository

4. Clinical Particulars 4.1 Therapeutic Indications

Ulcerative colitis or Crohn's Disease affecting the rectum.

4.2 Posology And Method Of Administration

The dose is adjusted according to the severity of the disease and the patient's tolerance of the drug.

Acute attack or relapse - Adults and the Elderly

Two suppositories are to be inserted in the morning and two at bedtime after defecation. After three weeks the dosage is gradually reduced as improvement occurs.

Adjustment to oral therapy - Adults and the Elderly

In severe generalised ulcerative colitis of the rectum or recto sigmoid, or in cases who are responding slowly to oral therapy, one or two suppositories may be given in the morning and at bedtime additional to oral therapy.

Children

The adult dose is reduced on the basis of body weight.

4.3 Contraindications

General

Because of lower absorption levels and shorter retention time in the body, Salazopyrin Suppositories give rise to fewer adverse events than equivalent treatment by mouth. However, because of the theoretical possibility that serious adverse events can arise from treatment from either route, the details below are based on adverse event reports to both oral and rectal treatment.

i) A known hypersensitivity to sulfasalazine, its metabolites or any of theexcipients as well as sulfonamides or salicylates.

ii) Use in infants under two years old.

iii) Porphyria.

4.4 Special Warnings And Precautions For Use

Complete blood counts (including differential white cell count), liver function tests and assessment of renal function (including urinalysis) should be performed in all patients before starting therapy with sulfasalazine, and frequently during the first 3 months of therapy. Thereafter, monitoring should be performed as clinically indicated. The patient should also be counselled to report immediately with any sore throat, fever, malaise, pallor, purpura, jaundice or unexpected non-specific illness during sulfasalazine treatment, this may indicate myelosuppression, haemolysis or hepatoxicity. Treatment should be stopped immediately while awaiting the results of blood tests. .

Sulfasalazine should not be given to patients with impaired hepatic or renal function or with blood dyscrasias, unless the potential benefit outweighs the risk.

Sulfasalazine should be given with caution to patients with severe allergy or bronchial asthma.

Use in children with the concomitant condition systemic onset juvenile rheumatoid arthritis may result in a serum sickness like reaction; therefore sulfasalazine is not recommended in these patients.

Since sulfasalazine may cause haemolytic anaemia, it should be used with caution in patients with G-6-PD deficiency.

Oral sulfasalazine inhibits the absorption and metabolism of folic acid and may cause folic acid deficiency potentially resulting in serious blood disorders (e.g., macrocytosis and pancytopenia), this can be normalised by administration of folic acid or folinic acid (leucovorin).

Because sulfasalazine causes crystalluria and kidney stone formation, adequate fluid intake should be ensured during treatment.

Oligospermia and infertility may occur in men treated with sulfasalazine. Discontinuation of the drug appears to reverse these effects within 2 to 3 months. As far as is know oligospermia has not occurred during therapy per rectum.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

There have been no adverse interactions reported, due to the drug largely remaining confined to the rectum. However, there is a potential for interaction as follows:

Reduced absorption of digoxin , resulting in non-therapeutic serum levels, has been reported when used concomitantly with oral sulfasalazine.

Sulfonamides bear certain chemical similarities to some oral hypoglycemic agents. Hypoglycemia has occurred in patients receiving sulfonamides. Patients receiving sulfasalazine and hypoglycemic agents should be closely monitored.

Due to inhibition of thiopurine methyltransferase by salazopyrin, bone marrow suppression and leucopenia have been reported when the thiopurine 6-mercaptopurine or it's prodrug, azathioprine, and oral salazopyrin were used concomitantly.

Coadministration of oral sulfasalazine and methotrexate to rheumatoid arthritis patients did not alter the pharmacokinetic disposition of the drugs. However, an increased incidence of gastrointestinal adverse events, especially nausea, was reported.

4.6 Pregnancy And Lactation

Pregnancy

Reproduction studies in rats and rabbits have revealed no evidence of harm to the fetus. Published data regarding use of sulfasalazine in pregnant women have revealed no evidence of teratogenic hazards. If sulfasalazine is used during pregnancy, the possibility of fetal harm appears remote. Oral sulfasalazine inhibits the absorption and metabolism of folic acid and may cause folic acid deficiency. Because the possibility of harm cannot be completely ruled out, sulfasalazine should be used during pregnancy only if clearly needed.

Lactation

Sulfasalazine and sulfapyridine are found in low levels in breast milk. Caution should be used, particularly if breastfeeding premature infants or those deficient in G-6-PD.

4.7 Effects On Ability To Drive And Use Machines

No specific effects.

4.8 Undesirable Effects

The following have been reported to sulfasalazine given orally or rectally. The drug rectally is well tolerated. Overall, about 75% of adverse drug reactions occur within three months of starting therapy and over 90% by six months. Some undesirable effects are dose-dependent and symptoms can often be alleviated by reduction of the dose.

General

Sulfasalazine is split by intestinal bacteria to sulfapyridine and 5-amino salicylate so adverse drugs reactions to either sulfonamide or salicylate are possible. Patients with slow acetylator status are more likely to experience adverse drug reactions related to sulfapyridine. The most commonly encountered adverse drugs reactions are nausea, headache, rash, loss of appetite and raised temperature.

Specific

The adverse reactions observed during clinical studies conducted with Sulfasalazine have been provided in a single list below by class and frequency (very common (

Additional reactions reported from post-marketing experience are included as frequency Not known (cannot be estimated from the available data) in the list below.

Body System

Adverse drug reactions

Infections and infestations

 

Not known

Pseudomembranous colitis

Blood and Lymphatic System Disorders

 

Common

Leukopenia

Uncommon

Thrombocytopenia*

Not known

Agranulocytosis, aplastic anemia, haemolytic anemia, Heinz body anaemia, hypoprothrombinaemia, lymphadenopathy, macrocytosis, megaloblastic anemia, methaemoglobinaemina, neutropenia, pancytopenia

Immune System Disorders:

 

Not known

Anaphylaxis, polyarteritis nodosa, serum sickness

Metabolism and Nutrition Disorders:

 

Not known

Loss of appetite

Psychiatric Disorders:

 

Common

Insomnia

Uncommon

Depression

Not known

Hallucinations

Nervous System Disorders:

 

Common

Dizziness, headache, taste disorders

Uncommon

Convulsions

Not known

Aseptic meningitis, ataxia, encephalopathy, peripheral neuropathy, smell disorders

Ear and Labyrinth Disorders:

 

Common

Tinnitus

Uncommo

Vertigo

Eye Disorders:

 

Common

Conjuctivial and scleral injection

Cardiac Disorders:

 

Not known

Allergic myocarditis, cyanosis, pericarditis

vascular Disorders:

 

Uncommon

Vasculitis

Respiratory, Thoracic and Mediastinal Disorders:

 

Common

Cough

Uncommon

Dyspnoea

Not known

Fibrosing alveolitis, eosinophilic infiltration, interstitial lung disease

Gastrointestinal Disorders:

 

Very Common

Gastric distress, nausea

Common

Abdominal pain, diarrhoea, vomiting, stomatitis

Not known

Aggravation of ulcerative colitis, pancreatitis, parotitis

Hepato-biliary Disorders:

 

Not known

Hepatic failure, fulminant hepatitis, hepatitis*

Skin and Subcutaneous Tissue Disorders:

 

Common

Pruritus

Uncommon

Alopecia, urticaria

Not known

Epidermal necrolysis (Lyell's syndrome), Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms (DRESS), toxic pustuloderma, erythema, exanthema, exfoliative dermatitis, periorbital oedema, lichen planus, photosensitivity

Musculoskeletal and Connective Tissue Disorders:

 

Common

Arthralgia

Not known

Systemic lupus erythematosus

Renal and Urinary Disorders:

 

Common

Proteinuria

Not known

Nephrotic syndrome, interstitial nephritis, crystalluria*, haematuria

Reproductive System and Breast Disorders:

 

Not known

Reversible oligospermia*

General Disorders and Administration Site Conditions:

 

Common

Fever

Uncommon

Facial oedema

Not known

Yellow discoloration of skin and body fluids

Investigations:

 

Uncommon

Elevation of liver enzymes

Not known

Induction of autoantibodies

* See Section 4.4 for further information

4.9 Overdose

Overdose with suppositories is unlikely. In the event, evacuate the bowel and treat supportively. The toxicity of sulphasalazine is low in acute dosage. There is no specific antidote.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

Therapeutic benefit of sulfasalazine in ulcerative colitis and Crohn's Disease appears to be due to a local action of the sulfasalazine and its split product 5-aminosalicylic acid on the mucous membrane and deeper colonic structures. Pharmacological actions noted for these compounds include inhibition of neutrophil activation, free radical scavenging, inhibition of superoxide production, inhibition of bacterial growth. Sulfasalazine inhibits 15-Prostaglandin dehydrogenase and slows prostaglandin metabolism. Lipoxygenase release in inflammatory cells is also depressed. NK cells and T cell proliferation are inhibited.

5.2 Pharmacokinetic Properties

There are considerable individual differences in the retention time of suppositories in volunteer studies. Consequently uptake values vary widely also. Given that the effect of the drug is almost certainly due to a local effect pharmacokinetics becomes less relevant to therapeutic action than to possible adverse effects related to systemic levels.

A study of five volunteers over three days following insertion of 2 x 0.5 g suppositories gave the following results:

Retention time: mean 8.9 hours (s.d. 5.2), serum concentration at 10 hours: sulfasalazine 1.7 mcg/ml (s.d. 0.46), sulfapyridine less than 1 mcg/ml. Percentage renal excretion: 10.2 (s.d. 4.3). Uptake as reflected by excretion is much below that of the oral rate and may explain the good tolerance of the dose form.

5.3 Preclinical Safety Data

In two-year carcinogenicity studies in rats and mice, sulfasalazine showed some evidence of carcinogenicity. In rats, there was a small increase in the incidence of transitional cell papillomas in the urinary bladder and kidney. The tumours were judged to be induced mechanically by calculi formed in the urine rather than through a direct genotoxic mechanism. In the mouse study, there was a significant increase in the incidence of hepatocellular adenoma or carcinoma. The mechanism of induction of hepatocellular neoplasia has been investigated and attributed to species-specific effects of sulfasalazine that are not relevant to humans.

Sulfasalazine did not show mutagenicity in the bacterial reverse mutation assay (Ames test) or in the L51784 mouse lymphoma cell assay at the HGPRT gene. It did not induce sister chromatid exchanges or chromosomal aberrations in cultured Chinese hamster ovary cells, and in vivo mouse bone marrow chromosomal aberration tests were negative. However, sulfasalazine showed positive or equivocal mutagenic responses in rat and mouse micronucleus assays, and in human lymphocyte sister chromatid exchange, chromosomal aberration and micronucleus assays. The ability of sulfasalazine to induce chromosome damage has been attributed to perturbation of folic acid levels rather than to a direct genotoxic mechanism.

Based on information from non-clinical studies, sulfasalazine is judged to pose no carcinogenic risk to humans. Sulfasalazine use has not been associated with the development of neoplasia in human epidemiology studies.

6. Pharmaceutical Particulars 6.1 List Of Excipients

Povidone

Adepa Solidus

6.2 Incompatibilities

Certain types of extended wear soft contact lenses may be permanently stained during therapy.

6.3 Shelf Life

Five years

6.4 Special Precautions For Storage

Do not store above 25°C.

6.5 Nature And Contents Of Container

PVC/Polyethylene laminate moulds

6.6 Special Precautions For Disposal And Other Handling

As the suppositories melt at body temperature they should be kept below 25°C and handled as little as possible before insertion so that they are firm.

Sulfasalazine is an orange dye, and care should thus be taken with clothing, bedding etc with regard to seepage or spillage.

Insertion

Empty the bowel if possible. Push the suppository through the anus with a finger, as far as possible. The urge to expel them will pass in a few minutes, once they have melted.

7. Marketing Authorisation Holder

Pfizer Limited

Ramsgate Road

Sandwich

Kent, CT13 9NJ

United Kingdom

8. Marketing Authorisation Number(S)

PL 00057/1042

9. Date Of First Authorisation/Renewal Of The Authorisation

12 August 2010

10. Date Of Revision Of The Text

12 August 2010

11. LEGAL CATEGORY

POM.

Ref: SZ 6_0 Supp UK


read more


Nuvelle Continuous


Due to regulatory changes, the content of the following Patient Information Leaflet may vary from the one found in your medicine pack. Please compare the 'Leaflet prepared/revised date' towards the end of the leaflet to establish if there have been any changes.

If you have any doubts or queries about your medication, please contact your doctor or pharmacist.

Nuvelle Continuous

Estradiol and norethisterone acetate

Read all of this booklet carefully before you start taking this medicine. Keep this booklet. You may need to read it again. If you have any further questions, ask your doctor or pharmacist. This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours. If any of the side effects get serious, or if you notice any side effects not listed in this booklet, please tell your doctor or pharmacist. In this booklet

1. WHAT NUVELLE CONTINUOUS IS AND WHAT IT IS USED FOR
2. BEFORE YOU TAKE NUVELLE CONTINUOUS
Medical history and regular check-ups
Do not take Nuvelle Continuous if you have
When you need to take special care with Nuvelle Continuous
Effect of Nuvelle Continuous on your heart or circulation
Nuvelle Continuous and blood clots
Nvelle Continuous and heart disease
Nuvelle Continuous and stroke
Nuvelle Continuous and cancer
Nuvelle Continuous and memory loss
Other conditions
Nuvelle Continuous and using other medicines
Pregnancy and breast-feeding
Driving or using machines
Important information about some of the ingredients of Nuvelle Continuous
3. HOW TO TAKE NUVELLE CONTINUOUS
About the pack
When to start
If you take more Nuvelle Continuous than you should
If you forget to take Nuvelle Continuous
If you stop taking Nuvelle Continuous
4. POSSIBLE SIDE EFFECTS
5. HOW TO STORE NUVELLE CONTINUOUS
6. FURTHER INFORMATION

What Nuvelle Continuous Is And What It Is Used For What Nuvelle Continuous is

Nuvelle Continuous is a Hormone Replacement Therapy (HRT). It contains two types of female hormone, an oestrogen and a progestogen. Your ovaries no longer make these hormones after the menopause.

What Nuvelle Continuous is used for

Nuvelle Continuous is used for the treatment of symptoms of the menopause such as hot flushes, difficulty in sleeping, nervousness, dizziness or vaginal dryness.

Nuvelle Continuous is also used for prevention of osteoporosis in postmenopausal women who have a high risk of fractures and who cannot be given other osteoporosis treatments.

Nuvelle Continuous is not a contraceptive.

Before You Take Nuvelle Continuous

As well as benefits, HRT has some risks which you need to consider when you’re deciding whether to take it, or whether to carry on taking it.

Medical history and regular check-ups

Before you start taking HRT, your doctor should ask you about your own and your family's medical history. Your doctor may decide to examine your breasts and/or your abdomen, and may do an internal examination - but only if these examinations are necessary for you, or if you have any special concerns.

Once you've started on HRT, you should see your doctor for regular check-ups (at least once a year). At these check-ups, your doctor may discuss with you the benefits and risks of continuing to take HRT.

Be sure to:

- go for regular breast screening and cervical smear tests.

- regularly check your breasts for any changes such as dimpling of the skin, changes in the nipple, or any lumps you can see or feel.

Do not take Nuvelle Continuous if you have: breast cancer, or a history of breast cancer cancer that depends on oestrogen to grow e.g. endometrial cancer (e.g. cancer of the lining of the womb) any unexplained vaginal bleeding untreated thickening of the lining of the womb (endometrial hyperplasia) ever had a blood clot in a vein (thrombosis) such as deep vein thrombosis or a pulmonary embolism, now or in the past or recently had a heart attack, stroke or angina had liver disease, and you have been told by your doctor that your liver function tests have not yet returned to normal porphyria (a rare, inherited blood pigment disorder) an allergy to oestrogens, to progestogens or to any other ingredient in Nuvelle Continuous been told to avoid lactose, that you have a rare hereditary condition called Lapp lactase deficiency or glucose-galactose malabsorption any reason to believe that you either are, or may be, pregnant, or if you are producing milk (lactating) and breast-feeding. (See also the 'Pregnancy and breast-feeding' section of this booklet)

- If any of the above conditions appear for the first time while taking Nuvelle Continuous, stop taking it at once and consult your doctor immediately.

When you need to take special care with Nuvelle Continuous

If you have ever had (e.g. during pregnancy or previous hormone treatment) any of the following, you may be closely supervised by your doctor because Nuvelle Continuous may worsen these conditions or cause them to return:

fibroids of the womb or any tissue of the lining of the womb at inappropriate places (endometriosis) a history of, or risk factors for, blood clotting (see "Nuvelle Continuous and blood clots") an increased risk for breast cancer (mother, sister or grandmother who has had breast cancer), or other tumours that depend on oestrogen to grow high blood pressure any disorder of the liver diabetes gallstones migraine or severe headaches systemic lupus erythematosus (SLE; a chronic inflammatory disease which can affect many parts of the body) a history of thickening of the lining of the womb (endometrial hyperplasia) epilepsy asthma deafness due to otosclerosis (excessive growth of the bones in the middle ear) Effect of Nuvelle Continuous on your heart or circulation

Nuvelle Continuous and blood clots

HRT may increase the risk of blood clots in the veins (also called deep vein thrombosis, or DVT) especially during the first year of taking it.

These blood clots are not always serious but if one travels to the lungs it can cause chest pain, sudden breathlessness, collapse or even death. This condition is called pulmonary embolism or PE.

DVT and PE are examples of a condition called venous thromboembolism, or VTE.

You are more likely to get a blood clot:

if you are seriously overweight if you have had a blood clot before if any of your close family have had blood clots if you have had one or more miscarriages if you have any blood clotting problem that needs treatment with a medicine such as warfarin if you're off your feet for a long time because of major surgery, injury or illness if you have a rare condition called SLE

If any of these things apply to you, talk to your doctor to see if you should take HRT.

Compare

Looking at women in their 50s who are not taking HRT – on average, over a 5-year period, 3 in 1000 would be expected to get a blood clot.

For women in their 50s who are taking HRT, the figure would be 7 in 1000.

Looking at women in their 60s who are not taking HRT – on average, over a 5-year period, 8 in 1000 would be expected to get a blood clot.

For women in their 60s who are taking HRT, the figure would be 17 in 1000.

If you get:

painful swelling in your leg sudden chest pain difficulty breathing

- See a doctor as soon as possible and do not take any more HRT until your doctor says you can. These may be signs of a blood clot.

If you're going to have surgery, make sure your doctor knows about it. You may need to stop taking HRT about 4 to 6 weeks before the operation, to reduce the risk of a blood clot. Your doctor will tell you when you can start taking HRT again.

Nuvelle Continuous and heart disease

HRT is not recommended for women who have heart disease, or have had heart disease recently. If you have ever had heart disease, talk to your doctor to see if you should be taking HRT.

HRT will not help to prevent heart disease.

Studies with one type of HRT (containing conjugated oestrogen plus the progestogen MPA) have shown that women may be slightly more likely to get heart disease during the first year of taking the medication. For other types of HRT, the risk is likely to be similar, although this is not yet certain.

If you get:

a pain in your chest that spreads to your arm or neck

- See a doctor as soon as possible and do not take any more HRT until your doctor says you can. This pain could be a sign of heart disease.

Nuvelle Continuous and stroke

Recent research suggests that HRT slightly increases the risk of having a stroke. Other things that can increase the risk of stroke include:

getting older high blood pressure smoking drinking too much alcohol an irregular heartbeat

If you are worried about any of these things, or if you have had a stroke in the past, talk to your doctor to see if you should take HRT.

Compare

Looking at women in their 50s who are not taking HRT – on average, over a 5-year period, 3 in 1000 would be expected to have a stroke.

For women in their 50s who are taking HRT, the figure would be 4 in 1000.

Looking at women in their 60s who are not taking HRT – on average, over a 5-year period, 11 in 1000 would be expected to have a stroke.

For women in their 60s who are taking HRT, the figure would be 15 in 1000.

If you get:

unexplained migraine-type headaches, with or without disturbed vision.

- See a doctor as soon as possible and do not take any more HRT until your doctor says you can. These headaches may be an early warning sign of a stroke.

Nuvelle Continuous and cancer

Breast cancer

Women who have breast cancer, or have had breast cancer in the past, should not take HRT.

Taking HRT for 5 years or more slightly increases the risk of breast cancer; so does having a later menopause. The risk for a post-menopausal woman taking HRT for 5 years is about the same as for a woman of the same age who's still having periods over that time and not taking HRT.

The extra risk of breast cancer goes up the longer you take HRT, but returns to normal within about 5 years after stopping HRT.

Your risk of breast cancer is also higher:

if you have a close relative (mother, sister or grandmother) who has had breast cancer if you are seriously overweight

If breast cancer is diagnosed in a woman taking HRT, it's more likely to be found before it has spread beyond the breast.

Compare

Looking at women aged 50 who are not taking HRT – on average, 45 in 1000 will be diagnosed with breast cancer by the time they reach the age of 70.

For women who start taking HRT at age 50 and take it for 5 years, the figure will be 47 in 1000

If they take HRT for 10 years, the figure will be 51 in 1000

If they take HRT for 15 years, the figure will be 57 in 1000

If you notice any changes in your breast, such as:

dimpling of the skin changes in the nipple any lumps you can see or feel

- Make an appointment to see your doctor as soon as possible.

Endometrial cancer (cancer of the lining of the womb)

Taking oestrogen-only HRT for a long time can increase the risk of cancer of the lining of the womb (the endometrium). Taking a progestogen as well as the oestrogen helps to lower the extra risk.

If you still have your womb, your doctor will prescribe a progestogen as well as oestrogen. These may be prescribed separately, or as a combined HRT product.

If you have had your womb removed (a hysterectomy), your doctor will discuss with you whether you can safely take oestrogen without a progestogen.

If you've had your womb removed because of endometriosis, any endometrium left in your body may be at risk. So your doctor may prescribe HRT that includes a progestogen as well as an oestrogen.

Nuvelle Continuous contains a progestogen.

Compare

Looking at women who still have a womb and who are not taking HRT– on average, 5 in 1000 will be diagnosed with endometrial cancer between the ages of 50 and 65.

For women who take oestrogen-only HRT the number will be 10 to 60 in 1000, depending on the dose and how long you take it.

The addition of a progestogen to oestrogen-only HRT greatly lowers the extra risk of endometrial cancer.

If you get breakthrough bleeding or spotting, it's usually nothing to worry about, especially during the first few months of taking HRT.

But if the bleeding or spotting:

carries on for more than the first few months starts after you've been on HRT for a while carries on even after you've stopped taking HRT

- Make an appointment to see your doctor. It could be a sign that your endometrium has become thicker.

Ovarian cancer

Ovarian cancer (cancer of the ovaries) is very rare, but it is serious. It can be difficult to diagnose, because there are often no obvious signs of the disease.

Some studies have indicated that taking oestrogen-only HRT for more than 5 years may increase the risk of ovarian cancer. It is not yet known whether other kinds of HRT increase the risk in the same way.

Nuvelle Continuous and memory loss

HRT will not prevent memory loss (dementia).

A study with one type of HRT (containing conjugated oestrogen plus the progestogen MPA) showed that women who started using this HRT after the age of 65 had a small increase in their risk of developing dementia. It is not known if this applies to other types of HRT, such as Nuvelle Continuous, or to younger women.

Other conditions If you have heart or kidney problems, your doctor should examine you carefully as oestrogens may cause fluid retention resulting in swelling. If you have pre-existing elevated triglycerides (a type of blood fat) your doctor should monitor you closely during oestrogen replacement therapy or HRT. Rare cases of large increase of plasma triglycerides (hypertriglyceridemia) leading to inflammation of the pancreas (pancreatitis) have been reported with oestrogen replacement therapy. If you have a tendency to develop blotchy brown patches (chloasma) on the face you should avoid exposure to the sun or ultraviolet light whilst using Nuvelle Continuous Your doctor will monitor you carefully if you have terminal kidney insufficiency as the blood levels of the active substances in Nuvelle Continuous will probably increase Nuvelle Continuous and using other medicines

Tell your doctor or pharmacist if you are using or have recently used any other medicines, including ones obtained without prescription.

The following may reduce the effects of Nuvelle Continuous:

medicines used for the treatment of: epilepsy (e.g. phenobarbital, phenytoin, carbamazepine) infections (e.g. rifampicin, rifabutin) HIV infection (e.g. nevirapine, efavirenz, nelfinavir, ritonavir) the herbal remedy St. John’s wort (Hypericum perforatum)

- Ask your doctor or pharmacist for advice before taking any medicine.

Pregnancy and breast-feeding

Nuvelle Continuous is for use in post-menopausal women. Do not take if you are pregnant or breast-feeding.

If you become pregnant, stop taking Nuvelle Continuous immediately and tell your doctor.

Driving or using machines

There is nothing to suggest that the use of Nuvelle Continuous affects driving or use of machines.

Important information about some of the ingredients of Nuvelle Continuous

Nuvelle Continuous contains lactose (a type of sugar). If you have an intolerance to some sugars, check with your doctor before taking Nuvelle Continuous.

HOW TO TAKE NUVELLE Continuous

Do not take Nuvelle Continuous until at least 12 months after your last natural period.

Nuvelle Continuous is not for use in children or adolescents.

About the pack

This pack is designed to help you remember to take your medicine. Each tablet is placed in a section marked with the day of the week on which it should be taken. The arrows between tablets show the order in which they must be taken. Your doctor may tell you when to start (see "when to start" for further information).

On the day you start, take your first pink tablet from the top row of tablets marked with the correct day. For instance, if you start on a Tuesday, press out the tablet from the blister marked 'TUE'.

Take one tablet each day, following the directions of the arrows, until you have finished all 28 tablets in the memo strip. It is best to take your tablet at the same time each day. You can take Nuvelle Continuous with or without food. The tablet should be swallowed whole with a glass of water or milk.

When you have finished each memo strip, start the next memo strip on the following day. Do not leave a break between memo strips. Tablet taking should be continuous and each memo strip will therefore be started on the same day of the week.

When to start

If you are not currently using an HRT preparation: start taking Nuvelle Continuous on any day.

If you have been taking other HRT preparations: carry on until you have finished your current pack and have taken all the tablets for that month. Take your first Nuvelle Continuous tablet the next day. Do not leave a break between your old tablets and the Nuvelle Continuous tablets.

If you take more Nuvelle Continuous than you should

If you have taken too many Nuvelle Continuous tablets by mistake, you may feel sick, vomit or have some menstruation-like bleeding. No specific treatment is necessary but you should consult your doctor or pharmacist if you are worried.

If you forget to take Nuvelle Continuous

If you forget to take a tablet at your usual time and you are less than 12 hours late, take it as soon as possible. Take the next tablet at the usual time.

If you are more than 12 hours late, leave the forgotten tablet in the pack. Continue to take the rest of the tablets at the usual time every day. You may experience irregular bleeding.

If you stop taking Nuvelle Continuous

You may begin to feel the usual symptoms of menopause again, which may include hot flushes, trouble sleeping, nervousness, dizziness or vaginal dryness. Consult your doctor or pharmacist if you want to stop taking Nuvelle Continuous tablets.

Nuvelle Continuous Side Effects

Like all medicines, Nuvelle Continuous can cause side effects, although not everybody gets them.

If any of the side effects gets serious, or if you notice any side effects not listed in this booklet, please tell your doctor or pharmacist.

Serious side effects associated with Hormone Replacement Therapy: blood clots in the veins cancer of the lining of the womb breast cancer heart disease stroke dementia

For more information about these side effects see Section 2.

Other side effects that have been linked to the use of Nuvelle Continuous and other oral hormone replacement therapies:

During the first few months of treatment you may experience some vaginal bleeding at unexpected times (breakthrough bleeding and spotting). These symptoms normally lessen with continued treatment. If they don’t, contact your doctor (see section 2 ‘Nuvelle Continuous and cancer/Endometrial cancer (cancer of the lining of the womb)’ for more information). breast pain, tenderness or enlargement, breast discharge painful periods, changes in vaginal secretions, pre-menstrual symptoms, increased size of fibroids in the womb, thrush, changes to the neck of the womb indigestion, a feeling of being bloated, passing wind, feeling or being sick, abdominal pain, gall bladder disease skin rashes or discolouration, itching, eczema, acne, unusual hair loss or hair growth, increased skin pigment especially on the face (chloasma – see section 2 ‘other conditions’ for more information), some rare skin problems headache, migraine, dizziness, anxiety or depressive symptoms, fatigue fast or irregular heartbeat (palpitations), high blood pressure, inflammation of veins usually in the legs fluid retention leading to swelling of parts of the body changes in body weight and sex drive, increased appetite muscle cramps, leg pains nose bleeds, visual disturbances (such as blurred vision), discomfort with contact lenses, allergic-type reactions, a worsening of glucose tolerance, bladder inflammation, rare disorders (porphyria, chorea). HOW TO STORE NUVELLE Continuous

Keep out of the reach and sight of children.

Do not use Nuvelle Continuous after the expiry date which is printed on the label after "EXP". The expiry date refers to the last day of the month stated.

Do not dispose of medicines down the drain or in the household rubbish. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

Further Information What Nuvelle Continuous contains

The active substances are estradiol (as hemihydrate) and norethisterone acetate.

The other ingredients are lactose monohydrate, maize starch, pre-gelatinized maize starch, povidone 25 000, talc, magnesium stearate (E572), methylhydroxypropyl cellulose, macrogol 6000, titanium dioxide (E171) and red ferric oxide pigments (E172).

What Nuvelle Continuous looks like and contents of the pack

Nuvelle Continuous tablets are pink film-coated tablets.

They are supplied in a blister pack (memo strip) containing 28 tablets with the days of the week printed on the blister.

Boxes containing three blister packs are available

Marketing Authorisation Holder Bayer PLC Bayer House Strawberry Hill Newbury Berkshire RG14 1JA Manufacturer Bayer Schering Pharma AG Berlin Germany

or

Schering GmbH & Co Produktions KG Weimar Germany

Date of the last revision of this booklet

April 2010.

Nuvelle is a trademark of Bayer Schering Pharma AG (formerly Schering AG).


read more


Emadine


emedastine difumarate
Dosage Form: ophthalmic solution
Emadine®
(emedastine difumarate ophthalmic solution) 0.05% DESCRIPTION

Emadine® (emedastine difumarate ophthalmic solution) 0.05% is a sterile ophthalmic solution containing emedastine, a relatively selective, H1-receptor antagonist for topical administration to the eyes. Emedastine difumarate is a white, crystalline, water-soluble fine powder with a molecular weight of 534.57. The chemical structure is presented below:

Structural Formula:

Chemical Name:

1H-benzimidazole,1-(2-ethoxyethyl)-2-(hexahydro-4-methyl-1H-1,4-diazepin-1-yl),(E)-2-butenedioate (1:2)

Each mL of Emadine contains: Active: 0.884 mg emedastine difumarate equivalent to 0.5 mg emedastine. Preservative: benzalkonium chloride 0.01%. Inactives: tromethamine; sodium chloride; hypromellose; hydrochloric acid/sodium hydroxide (adjust pH); and purified water. It has a pH of approximately 7.4 and an osmolality of approximately 300 mOsm/kg.

CLINICAL PHARMACOLOGY

Emedastine is a relatively selective, histamine H1 antagonist. In vitro examinations of emedastine's affinity for histamine receptors (H1: Ki=1.3 nM, H2: Ki=49,067 nM, and H3: Ki=12,430 nM) demonstrate relative selectivity for the H1 histamine receptor. In vivo studies have shown concentration-dependent inhibition of histamine-stimulated vascular permeability in the conjunctiva following topical ocular administration. Emedastine appears to be devoid of effects on adrenergic, dopaminergic and serotonin receptors.

Following topical administration in man, emedastine was shown to have low systemic exposure. In a study involving 10 normal volunteers dosed bilaterally twice daily for 15 days with emedastine ophthalmic solution 0.05%, plasma concentrations of the parent compound were generally below the quantitation limit of the assay (<0.3 ng/mL). Samples in which emedastine was quantifiable ranged from 0.30 to 0.49 ng/mL. The elimination half-life of oral emedastine in plasma is 3-4 hours. Approximately 44% of the oral dose is recovered in the urine over 24 hours with only 3.6% of the dose excreted as parent drug. Two primary metabolites, 5- and 6-hydroxyemedastine, are excreted in the urine as both free and conjugated forms. The 5'-oxoanalogs of 5- and 6-hydroxyemedastine and the N-oxide are also formed as minor metabolites. In an environmental study, patients with allergic conjunctivitis were treated with Emadine® (emedastine difumarate ophthalmic solution) 0.05% for six weeks. The results demonstrated that Emadine® (emedastine difumarate ophthalmic solution) 0.05% provides relief of the signs and symptoms of allergic conjunctivitis. In conjunctival antigen challenge studies, in which subjects were challenged with antigen both initially and up to four hours after dosing, Emadine® (emedastine difumarate ophthalmic solution) 0.05% was demonstrated to be significantly more effective than placebo in preventing ocular itching associated with allergic conjunctivitis.

INDICATIONS AND USAGE

Emadine® (emedastine difumarate ophthalmic solution) 0.05% is indicated for the temporary relief of the signs and symptoms of allergic conjunctivitis.

CONTRAINDICATIONS

Emadine® (emedastine difumarate ophthalmic solution) is contraindicated in persons with a known hypersensitivity to emedastine difumarate or any of its components.

WARNINGS

FOR TOPICAL OPHTHALMIC USE ONLY - NOT FOR INJECTION OR ORAL USE.

PRECAUTIONS Information for Patients:

To prevent contaminating the dropper tip and solution, care should be taken not to touch the eyelids or surrounding areas with the dropper tip of the bottle. Keep the bottle tightly closed when not in use. Do not use if the solution has become discolored.

Patients should be advised not to wear a contact lens if their eye is red. Emadine® (emedastine difumarate ophthalmic solution) 0.05% should not be used to treat contact lens related irritation. The preservative in Emadine® (emedastine difumarate ophthalmic solution) 0.05%, benzalkonium chloride, may be absorbed by soft contact lenses. Patients who wear soft contact lenses and whose eyes are not red, should be instructed to wait at least ten minutes after instilling Emadine® (emedastine difumarate ophthalmic solution) 0.05% before they insert their contact lenses.

Carcinogenesis, Mutagenesis, Impairment of Fertility:

Emedastine difumarate demonstrated no carcinogenicity effects in lifetime studies in mice and rats at dietary doses more than 80,000 times and more than 26,000 times the maximum recommended ocular human use level of 0.002 mg/kg/day for a 50 kg adult, respectively. Higher dose levels were not tested. Emedastine difumarate was determined to be nonmutagenic in an in vitro bacterial reverse mutation (Ames) test, an in vitro modification of the Ames test, an in vitro mammalian chromosome aberration test, an in vitro mammalian forward mutation test, an in vitro mammalian DNA repair synthesis test, an in vivo mammalian sister chromatid exchange test and an in vivo mouse micronucleus test. There was no evidence of impaired fertility or reproductive capacity in rats at 15,000 times the maximum recommended ocular human use level.

Pregnancy: Pregnancy Category B.

Teratology and peri- and post-natal studies have been conducted with emedastine difumarate in rats and rabbits. At 15,000 times the maximum recommended ocular human use level, emedastine difumarate was shown not to be teratogenic in rats and rabbits and no effects on peri/post-natal development were observed in rats. However, at 70,000 times the maximum recommended ocular human use level, emedastine difumarate was shown to increase the incidence of external, visceral and skeletal anomalies in rats. There are, however, no adequate and well controlled studies in pregnant women. Because animal studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers:

Emedastine has been identified in breast milk in rats following oral administration. It is not known whether topical ocular administration could result in sufficient systemic absorption to produce detectable quantities in breast milk. Nevertheless, caution should be exercised when Emadine® (emedastine difumarate ophthalmic solution) 0.05% is administered to a nursing mother.

Pediatric Use:

Safety and effectiveness in pediatric patients below the age of 3 years have not been established.

Geriatric Use:

No overall differences in safety or effectiveness have been observed between elderly and younger patients.

ADVERSE REACTIONS

In controlled clinical studies of Emadine® (emedastine difumarate ophthalmic solution) 0.05% lasting for 42 days, the most frequent adverse reaction was headache 11%. The following adverse experiences were reported in less than 5% of patients: Abnormal dreams, asthenia, bad taste, blurred vision, burning or stinging, corneal infiltrates, corneal staining, dermatitis, discomfort, dry eye, foreign body sensation, hyperemia, keratitis, pruritus, rhinitis, sinusitis and tearing. Some of these events were similar to the underlying disease being studied.

OVERDOSAGE

Somnolence and malaise have been reported following daily oral administration. Oral ingestion of the contents of a 15 mL DROP-TAINER® dispenser would be equivalent to 7.5 mg. In case of overdosage, treatment is symptomatic and supportive.

DOSAGE AND ADMINISTRATION

The recommended dose is one drop in the affected eye up to four times daily.

HOW SUPPLIED

Emadine® (emedastine difumarate ophthalmic solution) 0.05% is supplied as follows:

5 mL in opaque, plastic DROP-TAINER® dispenser.

5 mL: NDC 0065-0325-05

STORAGE: Store at 4° - 30°C (39° - 86°F).

Rx Only

U.S. Patents Nos. 5,441,958.

Revised: May 2009

ALCON LABORATORIES, INC.

6201 South Freeway

Fort Worth, Texas 76134 USA

1-800-757-9195

MedInfo@AlconLabs.com

Printed in USA

©2002, 2003, 2009 Alcon, Inc.

340326-0509

PRINCIPLE DISPLAY PANEL

NDC 0065-0325-05

Alcon®

Emadine®

(emedastine

Difumarate

Ophthalmic

solution) 0.05%

5 mL Sterile


Emadine 
emedastine difumarate  solution Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0065-0325 Route of Administration OPHTHALMIC DEA Schedule      Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength EMEDASTINE DIFUMARATE (EMEDASTINE) EMEDASTINE DIFUMARATE 0.884 mg  in 1 mL Inactive Ingredients Ingredient Name Strength TROMETHAMINE   SODIUM CHLORIDE   HYDROCHLORIC ACID   SODIUM HYDROXIDE   WATER   HYPROMELLOSES   BENZALKONIUM CHLORIDE   Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains          Packaging # NDC Package Description Multilevel Packaging 1 0065-0325-05 5 mL In 1 BOTTLE, PLASTIC None
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA020706 02/15/1998
Labeler - Alcon Laboratories, Inc. (008018525) Registrant - Alcon Laboratories, Inc. (008018525) Establishment Name Address ID/FEI Operations Alcon Laboratories, Inc. 008018525 MANUFACTURE Revised: 07/2011Alcon Laboratories, Inc. More Emadine resources Emadine Side Effects (in more detail) Emadine Dosage Emadine Use in Pregnancy & Breastfeeding Emadine Support Group 0 Reviews for Emadine - Add your own review/rating Emadine Concise Consumer Information (Cerner Multum) Emadine Monograph (AHFS DI) Emadine Advanced Consumer (Micromedex) - Includes Dosage Information Emadine Drops MedFacts Consumer Leaflet (Wolters Kluwer) Compare Emadine with other medications Conjunctivitis, Allergic
read more


LMX4 Lidocaine 4% w / w Cream


1. Name Of The Medicinal Product

LMX 4

Lidocaine 4%w/w Cream

2. Qualitative And Quantitative Composition

Lidocaine 4%w/w

For excipients, see 6.1

3. Pharmaceutical Form

Cream

A white to off-white yellowish cream

4. Clinical Particulars 4.1 Therapeutic Indications

Local anaesthetic for topical use to produce surface anaesthesia of the skin prior to venous cannulation or venipuncture.

4.2 Posology And Method Of Administration

For cutaneous use only.

Adults, including elderly, and children over one month of age.

Apply 1g to 2.5g of cream onto the skin to cover a 2.5cm x 2.5cm (6.25cm2) area where venous cannulation or venipuncture will occur. No more than 1g of cream should be applied to infants below the age of 1 year. 1g of cream equates to approximately 5cm of cream squeezed from the 5g tube or 3.5cm from the 30g tube.

The cream should remain undisturbed and the area can be covered with an occlusive dressing to prevent disturbance or interference by the patient or other external factors. Adequate anaesthesia should be obtained after 30 minutes, but the LMX4 Cream may be applied for up to 5 hours under a dressing. Prior to starting the procedure, the LMX 4 Cream should be removed using a clean gauze swab and the site for venous cannulation or venipuncture prepared in the usual manner. The procedure should be initiated approximately 5 minutes after the cream has been removed. Maximum application time for 1 month upto 3 month infant should not exceed 60 minutes. Maximum application time for 3 month upto 12 month infant should not exceed 4 hours. Maximum application for 12 month infant – adult should not exceed 5 hours.

4.3 Contraindications

Hypersensitivity to the active substance, or any of the amide-type local anaesthetics, or any of the excipients.

4.4 Special Warnings And Precautions For Use

For external use only.

Avoid contact with eyes.

Do not apply to irritated skin or if excessive irritation develops. If condition worsens, or if symptoms persist unaltered for more than seven days or clear up and occur again within only a few days, discontinue use of this product and consult a doctor.

Do not use in large quantities, particularly over raw or blistered areas.

LMX 4 contains propylene glycol which may cause skin irritation.

LMX 4 has not been applied to wounds, mucous membranes or in areas of atopic dermatitis as there are no clinical data in relation to these.

Anaesthetic efficacy during the heel lancing of neonates has not been studied.

Application of lidocaine to larger areas or for longer times than those recommended could result in sufficient absorption of lidocaine resulting in serious adverse effects.

Studies in laboratory animals (guinea pigs) have shown that lidocaine has an ototoxic effect when instilled into the middle ear. In these same studies, animals exposed to lidocaine in the external auditory canal only showed no abnormality. Lidocaine should not be used in any clinical situation in which its penetration or migration beyond the tympanic membrane into the middle ear is possible.

Dermal application of lidocaine may cause transient local blanching followed by transient erythema.

PRECAUTIONS

General: Repeated doses of lidocaine may increase blood levels of lidocaine. Lidocaine should be used with caution in patients who may be more sensitive to the systemic effects of lidocaine including acutely ill, debilitated, or elderly patients.

Lidocaine coming in contact with the eye should be avoided because animal studies have demonstrated severe eye irritation. Also the loss of protective reflexes can permit corneal irritation and potential abrasion. Absorption of lidocaine in conjunctival tissues has not been determined. If eye contact occurs, immediately wash out the eye with water or saline and protect the eye until sensation returns.

Patients allergic to para-aminobenzoic acid derivatives (procaine, tetracaine, benzocaine, etc.) have not shown cross sensitivity to lidocaine; however, lidocaine should be used with caution in patients with a history of drug sensitivities, especially if the etiologic agent is uncertain. Patients with severe hepatic disease, because of their inability to metabolize local anaesthetics normally, are at greater risk of developing toxic plasma concentrations of lidocaine.

When lidocaine is used, the patient should be aware that the production of dermal analgesia may be accompanied by the block of all sensations in the treated skin. For this reason, the patient should avoid inadvertent trauma to the treated area by scratching, rubbing, or exposure to extreme hot or cold temperatures until complete sensation has returned.

Lidocaine has bactericidal and antiviral properties in concentrations above 0.5%. For this reason, the results of intra-cutaneous injections of live vaccines (such as BCG vaccination) should be monitored.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Lidocaine should be used with caution in patients receiving Class I anti-arrhythmic drugs (such as tocainide and mexiletine) since the toxic effects are additive and generally synergistic.

The risk of additional systemic toxicity should be considered when large doses of LMX 4 are applied to patients already using other local anaesthetics.

4.6 Pregnancy And Lactation

There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, lidocaine should be used during pregnancy only if clearly needed.

Lidocaine is not contraindicated in labour and delivery. Should LMX 4 be used concomitantly with other products containing lidocaine, total doses contributed by all formulations must be considered.

Lidocaine can cross the placental barrier.

Lidocaine is excreted in human milk. Therefore, caution should be exercised when LMX 4 is administered to a nursing mother since the milk:plasma ratio of lidocaine is 0.4.

4.7 Effects On Ability To Drive And Use Machines

None known.

4.8 Undesirable Effects

Common side effects (>1/100) can include irritation, redness, itching, or rash.

In rare cases local anaesthetics have been associated with allergic reactions including anaphylactic shock.

Corneal irritation after accidental eye exposure.

4.9 Overdose

Overdose with LMX 4 cream is unlikely but signs of systemic toxicity would be consistent with those of lidocaine.

An indication of systemic toxicity may include blurred vision, dizziness or drowsiness, difficulty breathing, trembling, chest pain, or irregular heartbeat.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

Anaesthetics for topical use, lidocaine, ATC Code: D04A B 01

Lidocaine applied to intact skin provides dermal analgesia by a release of lidocaine from the cream into the epidermal and dermal layers of the skin, and by the accumulation of lidocaine in the vicinity of pain receptors and nerve endings. Lidocaine is an amide-type local anaesthetic agent which stabilises neuronal membranes by inhibiting the ionic fluxes required for the initiation and conduction of impulses, thereby effecting local anaesthetic action. The onset, depth and duration of dermal analgesia provided by lidocaine depend primarily on the duration of application. LMX 4 may cause transient peripheral vasoconstriction followed by transient vasodilation at the application site.

5.2 Pharmacokinetic Properties

The amount of lidocaine systemically absorbed is directly related to both the duration of application and to the area over which it is applied. It is not known if it is metabolized into the skin. Lidocaine is metabolized rapidly by the liver to a number of metabolites including monoethylglycinexylidide (MEGX) and glycinexylidide (GX), both of which have pharmacologic activity similar to, but less potent to that of lidocaine. The metabolite, 2,6-xylidine, has unknown pharmacologic activity but is carcinogenic in rats. Following intravenous administration, MEGX and GX concentrations in serum range from 11 to 36% and from 5 to 11% of concentrations, respectively. The half-life of lidocaine elimination from the plasma following IV administration is approximately 65 to 150 minutes (mean 110, ±24 SD, n=13). This half-life may be increased in cardiac or hepatic dysfunction. More than 98% of an absorbed dose of can be recovered in the urine as metabolites or parent drug. The systemic clearance is 10 to 20 mL/min/kg (mean 13, ±3 SD, n=13).

When applied topically to intact skin, the absorption of lidocaine is very low. Increased absorption is therefore to be expected when applied to mucosa or previously damaged skin.

The maximum plasma level of active ingredient was very low (0.3 µg/ml or less) in a study investigating the application of LMX 4 in children of different ages. It was well below the toxically effective plasma level of ingredients.

5.3 Preclinical Safety Data

The mutagenic potential of lidocaine HCl has been tested in the Ames Salmonella/mammalian microsome test and by analysis of structural chromosome aberrations in human lymphocytes in vitro, and by mouse micronucleus test in vivo. There was no indication in these tests of any mutagenic effects. The mutagenicity of 2,6-xylidine, a metabolite of lidocaine, has been studied in different tests with mixed results. The compound was found to be weakly mutagenic in the Ames test only under metabolic activation conditions. In addition, 2,6-xylidine was observed to be mutagenic at the thymidine kinase locus, with or without activation, and induced chromosome aberrations and sister chromatic exchanges at concentrations at which the drug precipitated out of the solution (1.2 mg/ml). No evidence of genotoxicity was found in the in vivo assays measuring unscheduled DNA synthesis in rat hepatocytes, chromosome damage in polychromatic erythrocytes or preferential killing of DNA repair-deficient bacteria in liver, lung, kidney, testes and blood extracts from mice. However, covalent binding studies of DNA from liver and ethmoid turbinates in rats indicate that 2,6-xylidine may be genotoxic under certain conditions in vivo.

6. Pharmaceutical Particulars 6.1 List Of Excipients

Benzyl Alcohol

Carbomers

Cholesterol

Phospholipon 80H (Hydrogenated Soy Lecithin)

Polysorbate 80 (Tween 80)

Propylene Glycol

Trolamine

Vitamin E Acetate

Purified Water

6.2 Incompatibilities

Not applicable

6.3 Shelf Life

Unopened:

Two years

Opened:

3 months

6.4 Special Precautions For Storage

Do not store above 25°C.

6.5 Nature And Contents Of Container

The pack sizes are 5g and 30g.

Both packs comprise of an aluminium tube with an epoxyphenolic internal lacquer, fitted with a polypropylene cap.

The following packaging options are approved but not all of these packaging options may be marketed:

1) A carton containing one 5g tube.

2) A carton containing five 5g tubes.

3) A carton containing one 5g tube with two Tegaderm® occlusive dressings.

4) A carton containing five 5g tubes with ten Tegaderm® occlusive dressings.

5) A carton containing one 30g tube.

6.6 Special Precautions For Disposal And Other Handling

No special requirements

7. Marketing Authorisation Holder

Ferndale Pharmaceuticals Ltd

12 York Place

Leeds

LS1 2DS

United Kingdom

8. Marketing Authorisation Number(S)

PL 20685/0034

9. Date Of First Authorisation/Renewal Of The Authorisation

20/11/2007

10. Date Of Revision Of The Text

15/03/2011


read more


Halobetasol Propionate Ointment


Generic Name: halobetasol propionate
Dosage Form: ointment
Halonate (halobetasol Propionate ointmanet 0.05%)

Halonate Halobetasol Propionate Ointment, 0.05% contains halobetasol propionate, a synthetic corticosteroid
for topical dermatological use. The corticosteroids constitute a class of primarily synthetic
steroids used topically as an anti-inflammatory and anti-pruritic agent.

Chemically halobetasol propionate is 21-chloro-6?, 9-difluoro-11?,17-dihydroxy-16?-methylpregna-1,
4-diene-3-20-dione, 17-propionate, C25H31ClF2O5. It has the following structural formula:


Halobetasol propionate has the molecular weight of 485. It is a white crystalline powder insoluble in water.
Each gram of Halobetasol Propionate Ointment contains 0.5 mg/g of halobetasol propionate in a
base of aluminum stearate, beeswax, pentaerythritol cocoate, petrolatum, propylene glycol, sorbitan
sesquioleate, and stearyl citrate.
Like other topical corticosteroids, halobetasol propionate has anti-inflammatory, antipruritic and
vasoconstrictive actions. The mechanism of the anti-inflammatory activity of the topical corticosteroids,
in general, is unclear. However, corticosteroids are thought to act by the induction of
phospholipase A2 inhibitory proteins, collectively called lipocortins. It is postulated that these proteins
control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes
by inhibiting the release of their common precursor arachidonic acid. Arachidonic acid is
released from membrane phospholipids by phospholipase A2. The extent of percutaneous absorption of topical corticosteroids is determined by many factors
including the vehicle and the integrity of the epidermal barrier. Occlusive dressings with hydrocortisone
for up to 24 hours have not been demonstrated to increase penetration; however, occlusion
of hydrocortisone for 96 hours markedly enhances penetration. Topical corticosteroids can be absorbed
from normal intact skin. Inflammation and/or other disease processes in the skin may increase percutaneous
absorption.
Human and animal studies indicate that less than 6% of the applied dose of halobetasol propionate
enters the circulation within 96 hours following topical administration of the ointment.
Studies performed with Halobetasol Propionate Ointment indicate that it is in the super-high range
of potency as compared with other topical corticosteroids. Halobetasol Propionate Ointment 0.05% is a superhigh potency corticosteroid indicated for the relief
of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses. Treatment
beyond two consecutive weeks is not recommended, and the total dosage should not exceed 50 g/week
because of the potential for the drug to suppress the hypothalamic-pituitary-adrenal (HPA) axis. Use
in children under 12 years of age is not recommended.
As with other highly active corticosteroids, therapy should be discontinued when control has been
achieved. If no improvement is seen within 2 weeks, reassessment of the diagnosis may be
necessary.

Halobetasol Propionate Ointment is contraindicated in those patients with a history of hypersensitivity
to any of the components of the preparation.

General:  Systemic absorption of topical corticosteroids can produce reversible hypothalamic-pituitary-adrenal
(HPA) axis suppression with the potential for glucocorticosteroid insufficiency after withdrawal of
treatment. Manifestations of Cushing’s syndrome, hyperglycemia, and glucosuria can also be produced
in some patients by systemic absorption of topical corticosteroids while on treatment.
Patients applying a topical steroid to a large surface area or to areas under occlusion should be evaluated
periodically for evidence of HPA axis suppression. This may be done by using the ACTH stimulation,
A.M. plasma cortisol, and urinary free-cortisol tests.  Patients receiving super potent corticosteroids
should not be treated for more than 2 weeks at a time and only small areas should be treated at any one
time due to the increased risk of HPA suppression.
Halobetasol Propionate Ointment produced HPA axis suppression when used in divided doses at 7
grams per day for one week in patients with psoriasis. These effects were reversible upon discontinuation
of treatment.
If HPA axis suppression is noted, an attempt should be made to withdraw the drug, to reduce the
frequency of application, or to substitute a less potent corticosteroid. Recovery of HPA axis function
is generally prompt upon discontinuation of topical corticosteroids. Infrequently, signs and symptoms
of glucocorticosteroid insufficiency may occur requiring supplemental systemic corticosteroids.
For information on systemic supplementation, see prescribing information for those products.
Pediatric patients may be more susceptible to systemic toxicity from equivalent doses due to their
larger skin surface to body mass ratios (see PRECAUTIONS:Pediatric Use).
If irritation develops, Halobetasol Propionate Ointment should be discontinued and appropriate
therapy instituted. Allergic contact dermatitis with corticosteroids is usually diagnosed by observing
failure to heal rather than noting a clinical exacerbation as with most topical products not containing
corticosteroids. Such an observation should be corroborated with appropriate diagnostic patch testing.
If concomitant skin infections are present or develop, an appropriate antifungal or anti-bacterial
agent should be used. If a favorable response does not occur promptly, use of Halobetasol Propionate
Ointment should be discontinued until the infection has been adequately controlled.
Halobetasol Propionate Ointment should not be used in the treatment of rosacea or perioral dermatitis,
and it should not be used on the face, groin,or in the axillae.

Patients using topical corticosteroids should receive the following information and instructions:
1) The medication is to be used as directed by the physician. It is for external use only. Avoid contact
with the eyes.
2) The medication should not be used for any disorder other than that for which it was prescribed.
3) The treated skin area should not be bandaged, otherwise covered or wrapped, so as to be
occlusive unless directed by the physician.
4) Patients should report to their physician any signs of local adverse reactions.
The following tests may be helpful in evaluating patients for HPA axis suppression: ACTH-stimulation
test; A.M. plasma cortisol test; Urinary freecortisol test.

Long-term animal studies have not been performed to evaluate the carcinogenic potential of halobetasol
propionate.

Positive mutagenicity effects were observed in two genotoxicity assays. Halobetasol propionate
was positive in a Chinese hamster micronucleus test, and in a mouse lymphoma gene mutation
assay in vitro.

Studies in the rat following oral administration at dose levels up to 50 ?g/kg/day indicated no impairment
of fertility or general reproductive performance.

In other genotoxicity testing, halobetasol propionate was not found to be genotoxic in the
Ames/Salmonella assay, in the sister chromatid exchange test in somatic cells of the Chinese hamster,
in chromosome aberration studies of germinal and somatic cells of rodents, and in a mammalian spot
test to determine point mutations.

Teratogenic effects: Pregnancy Category C: Corticosteroids have been shown to be teratogenic
in laboratory animals when administered systemically at relatively low dosage levels. Some corticosteroids
have been shown to be teratogenic after dermal application in laboratory animals.
Halobetasol propionate has been shown to be teratogenic in SPF rats and chinchilla-type rabbits
when given systemically during gestation at doses of 0.04 to 0.1 mg/kg in rats and 0.01 mg/kg in
rabbits. These doses are approximately 13, 33 and 3 times, respectively, the human topical dose of
Halobetasol Propionate Ointment. Halobetasol propionate was embryotoxic in rabbits but not in rats.
Cleft palate was observed in both rats and rabbits. Omphalocele was seen in rats, but not in rabbits.
There are no adequate and well-controlled studies of the teratogenic potential of halobetasol propionate
in pregnant women. Halobetasol Propionate Ointment should be used during pregnancy only if
the potential benefit justifies the potential risk to the fetus.

Systemically administered corticosteroids appear in human milk and could suppress growth, interfere
with endogenous corticosteroid production, or cause other untoward effects. It is not known
whether topical administration of corticosteroids could result in sufficient systemic absorption to
produce detectable quantities in human milk. Because many drugs are excreted in human milk,
caution should be exercised when Halobetasol Propionate Ointment is administered to a nursing
woman.

Safety and effectiveness of Halobetasol Propionate Ointment in pediatric patients have not been established
and use in pediatric patients under 12 is not recommended. Because of a higher ratio of skin
surface area to body mass, pediatric patients are at a greater risk than adults of HPA axis suppression
and Cushing’s syndrome when they are treated with topical corticosteroids. They are therefore also at
greater risk of adrenal insufficiency during or after withdrawal of treatment. Adverse effects including
striae have been reported with inappropriate use of topical corticosteroids in infants and children.

HPA axis suppression, Cushing’s syndrome, linear growth retardation, delayed weight gain and
intracranial hypertension have been reported in children receiving topical corticosteroids. Manifestations
of adrenal suppression in children include low plasma cortisol levels and an absence of
response to ACTH stimulation. Manifestations of intracranial hypertension include bulging fontanelles,
headaches, and bilateral papilledema. Of approximately 850 patients treated with Halobetasol Propionate Ointment in clinical studies,
21% were 61 years and over and 6% were 71 years and over. No overall differences in safety or effectiveness
were observed between these patients and younger patients; and other reported clinical experience
has not identified differences in responses between the elderly and younger patients, but
greater sensitivity of some older individuals cannot be ruled out. In controlled clinical trials, the most frequent adverse events reported for Halobetasol Propionate
Ointment included stinging or burning in 1.6% of the patients. Less frequently reported adverse reactions
were pustulation, erythema, skin atrophy, leukoderma, acne, itching, secondary infection,
telangiectasia, urticaria, dry skin, miliaria, paresthesia, and rash.
The following additional local adverse reactions are reported infrequently with topical corticosteroids,
and they may occur more frequently with high potency corticosteroids, such as Halobetasol
Propionate Ointment. These reactions are listed in an approximate decreasing order of occurrence:
folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic
contact dermatitis, secondary infection, striae and miliaria.
Topically applied Halobetasol Propionate Ointment can be absorbed in sufficient amounts to produce
systemic effects (see PRECAUTIONS).
Apply a thin layer of Halobetasol Propionate Ointment to the affected skin once or twice daily, as
directed by your physician, and rub in gently and completely.
Halobetasol Propionate Ointment is a super-high potency topical corticosteroid; therefore, treatment
should be limited to two weeks, and amounts greater than 50 g/wk should not be used. As with
other corticosteroids, therapy should be discontinued when control is achieved. If no improvement is
seen within 2 weeks, reassessment of diagnosis may be necessary.
Halobetasol Propionate Ointment should not be used with occlusive dressings. Halonate™ is supplied in the following:
(NDC 68712-042-01) one 50 g tube of Halobetasol Propionate Ointment 0.05% packaged with one
4 oz can of ammonium lactate mousse 12%
STORAGE: Store between 15°C and 30°C (59°F and 86°F).
Manufactured by:
G and W Laboratories, Inc.
South Plainfield, NJ  07080
Manufactured for:
JSJ Pharmaceuticals
Charleston, SC  29401
1-800-499-4468
www.jsjpharm.com


HALONATE PAC 
halobetasol   ointment Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 68712-042 Route of Administration TOPICAL DEA Schedule      Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength HALOBETASOL PROPIONATE (HALOBETASOL ) HALOBETASOL PROPIONATE 0.5 mg  in 1 g Inactive Ingredients Ingredient Name Strength ALUMINUM STEARATE   YELLOW WAX   PENTAERYTHRITOL   PETROLATUM   PROPYLENE GLYCOL   Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains          Packaging # NDC Package Description Multilevel Packaging 1 68712-042-01 50 g In 1 TUBE None
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA077721 05/01/2010
Labeler - JSJ Pharmaceuticals (615074866) Establishment Name Address ID/FEI Operations G and W Laboratories Inc. 001271188 manufacture Revised: 07/2010JSJ Pharmaceuticals
More Halobetasol Propionate Ointment resources Halobetasol Propionate Ointment Side Effects (in more detail) Halobetasol Propionate Ointment Use in Pregnancy & Breastfeeding Halobetasol Propionate Ointment Drug Interactions Halobetasol Propionate Ointment Support Group 14 Reviews for Halobetasol Propionate - Add your own review/rating Compare Halobetasol Propionate Ointment with other medications Atopic Dermatitis Dermatitis Eczema Psoriasis
read more


Halonate


halobetasol propionate
Dosage Form: ointment
Halonate (halobetasol Propionate ointmanet 0.05%) Description

Halonate Halobetasol Propionate Ointment, 0.05% contains halobetasol propionate, a synthetic corticosteroid for topical dermatological use. The corticosteroids constitute a class of primarily synthetic steroids used topically as an anti-inflammatory and anti-pruritic agent.  Chemically halobetasol propionate is 21-chloro-6?, 9-difluoro-11?,17-dihydroxy-16?-methylpregna-1, 4-diene-3-20-dione, 17-propionate, C25H31ClF2O5. It has the following structural formula:


Halobetasol propionate has the molecular weight of 485. It is a white crystalline powder insoluble in water.  Each gram of Halobetasol Propionate Ointment contains 0.5 mg/g of halobetasol propionate in a
base of aluminum stearate, beeswax, pentaerythritol cocoate, petrolatum, propylene glycol, sorbitan sesquioleate, and stearyl citrate.
Clinical Pharmacology Like other topical corticosteroids, halobetasol propionate has anti-inflammatory, antipruritic and vasoconstrictive actions. The mechanism of the anti-inflammatory activity of the topical corticosteroids, in general, is unclear. However, corticosteroids are thought to act by the induction of phospholipase A2 inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A2. Pharmacokinetics The extent of percutaneous absorption of topical corticosteroids is determined by many factors including the vehicle and the integrity of the epidermal barrier. Occlusive dressings with hydrocortisone for up to 24 hours have not been demonstrated to increase penetration; however, occlusion of hydrocortisone for 96 hours markedly enhances penetration. Topical corticosteroids can be absorbed from normal intact skin. Inflammation and/or other disease processes in the skin may increase percutaneous absorption.
Human and animal studies indicate that less than 6% of the applied dose of halobetasol propionate enters the circulation within 96 hours following topical administration of the ointment. Studies performed with Halobetasol Propionate Ointment indicate that it is in the super-high range of potency as compared with other topical corticosteroids. Indications and Usage Halobetasol Propionate Ointment 0.05% is a superhigh potency corticosteroid indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses. Treatment beyond two consecutive weeks is not recommended, and the total dosage should not exceed 50 g/week because of the potential for the drug to suppress the hypothalamic-pituitary-adrenal (HPA) axis. Use in children under 12 years of age is not recommended.
As with other highly active corticosteroids, therapy should be discontinued when control has been achieved. If no improvement is seen within 2 weeks, reassessment of the diagnosis may be necessary. Contraindications

Halobetasol Propionate Ointment is contraindicated in those patients with a history of hypersensitivity to any of the components of the preparation.

Precautions
General:  Systemic absorption of topical corticosteroids can produce reversible hypothalamic-pituitary-adrenal (HPA) axis suppression with the potential for glucocorticosteroid insufficiency after withdrawal of treatment. Manifestations of Cushing’s syndrome, hyperglycemia, and glucosuria can also be produced in some patients by systemic absorption of topical corticosteroids while on treatment.
Patients applying a topical steroid to a large surface area or to areas under occlusion should be evaluated periodically for evidence of HPA axis suppression. This may be done by using the ACTH stimulation, A.M. plasma cortisol, and urinary free-cortisol tests.  Patients receiving super potent corticosteroids should not be treated for more than 2 weeks at a time and only small areas should be treated at any one time due to the increased risk of HPA suppression.
Halobetasol Propionate Ointment produced HPA axis suppression when used in divided doses at 7 grams per day for one week in patients with psoriasis. These effects were reversible upon discontinuation of treatment.
If HPA axis suppression is noted, an attempt should be made to withdraw the drug, to reduce the frequency of application, or to substitute a less potent corticosteroid. Recovery of HPA axis function is generally prompt upon discontinuation of topical corticosteroids. Infrequently, signs and symptoms of glucocorticosteroid insufficiency may occur requiring supplemental systemic corticosteroids. For information on systemic supplementation, see prescribing information for those products.
Pediatric patients may be more susceptible to systemic toxicity from equivalent doses due to their larger skin surface to body mass ratios (see PRECAUTIONS: Pediatric Use).
If irritation develops, Halobetasol Propionate Ointment should be discontinued and appropriate therapy instituted. Allergic contact dermatitis with corticosteroids is usually diagnosed by observing failure to heal rather than noting a clinical exacerbation as with most topical products not containing corticosteroids. Such an observation should be corroborated with appropriate diagnostic patch testing. If concomitant skin infections are present or develop, an appropriate antifungal or anti-bacterial agent should be used. If a favorable response does not occur promptly, use of Halobetasol Propionate Ointment should be discontinued until the infection has been adequately controlled.
Halobetasol Propionate Ointment should not be used in the treatment of rosacea or perioral dermatitis, and it should not be used on the face, groin,or in the axillae.
Information for Patients
Patients using topical corticosteroids should receive the following information and instructions:
1) The medication is to be used as directed by the physician. It is for external use only. Avoid contact
with the eyes.
2) The medication should not be used for any disorder other than that for which it was prescribed.
3) The treated skin area should not be bandaged, otherwise covered or wrapped, so as to be
occlusive unless directed by the physician.
4) Patients should report to their physician any signs of local adverse reactions.
Laboratory Tests The following tests may be helpful in evaluating patients for HPA axis suppression: ACTH-stimulation test; A.M. plasma cortisol test; Urinary freecortisol test. Carcinogenesis & Mutagenesis & Imprairment of Fertility Section

Long-term animal studies have not been performed to evaluate the carcinogenic potential of halobetasol propionate.

Positive mutagenicity effects were observed in two genotoxicity assays. Halobetasol propionate was positive in a Chinese hamster micronucleus test, and in a mouse lymphoma gene mutation assay in vitro.

Studies in the rat following oral administration at dose levels up to 50 ?g/kg/day indicated no impairment of fertility or general reproductive performance.

In other genotoxicity testing, halobetasol propionate was not found to be genotoxic in the Ames/Salmonella assay, in the sister chromatid exchange test in somatic cells of the Chinese hamster, in chromosome aberration studies of germinal and somatic cells of rodents, and in a mammalian spot test to determine point mutations.

Pregnancy Teratogenic effects: Pregnancy Category C: Corticosteroids have been shown to be teratogenic in laboratory animals when administered systemically at relatively low dosage levels. Some corticosteroids have been shown to be teratogenic after dermal application in laboratory animals.
Halobetasol propionate has been shown to be teratogenic in SPF rats and chinchilla-type rabbits when given systemically during gestation at doses of 0.04 to 0.1 mg/kg in rats and 0.01 mg/kg in rabbits. These doses are approximately 13, 33 and 3 times, respectively, the human topical dose of Halobetasol Propionate Ointment. Halobetasol propionate was embryotoxic in rabbits but not in rats.
Cleft palate was observed in both rats and rabbits. Omphalocele was seen in rats, but not in rabbits.
There are no adequate and well-controlled studies of the teratogenic potential of halobetasol propionate in pregnant women. Halobetasol Propionate Ointment should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Nursing Mothers

Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in human milk. Because many drugs are excreted in human milk, caution should be exercised when Halobetasol Propionate Ointment is administered to a nursing woman.

Pediatric Use

Safety and effectiveness of Halobetasol Propionate Ointment in pediatric patients have not been established and use in pediatric patients under 12 is not recommended. Because of a higher ratio of skin surface area to body mass, pediatric patients are at a greater risk than adults of HPA axis suppression and Cushing’s syndrome when they are treated with topical corticosteroids. They are therefore also at greater risk of adrenal insufficiency during or after withdrawal of treatment. Adverse effects including striae have been reported with inappropriate use of topical corticosteroids in infants and children.

HPA axis suppression, Cushing’s syndrome, linear growth retardation, delayed weight gain and intracranial hypertension have been reported in children receiving topical corticosteroids. Manifestations
of adrenal suppression in children include low plasma cortisol levels and an absence of response to ACTH stimulation. Manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema. Geriatric Use Of approximately 850 patients treated with Halobetasol Propionate Ointment in clinical studies,
21% were 61 years and over and 6% were 71 years and over. No overall differences in safety or effectiveness
were observed between these patients and younger patients; and other reported clinical experience
has not identified differences in responses between the elderly and younger patients, but
greater sensitivity of some older individuals cannot be ruled out. Adverse Reactions In controlled clinical trials, the most frequent adverse events reported for Halobetasol Propionate Ointment included stinging or burning in 1.6% of the patients. Less frequently reported adverse reactions were pustulation, erythema, skin atrophy, leukoderma, acne, itching, secondary infection, telangiectasia, urticaria, dry skin, miliaria, paresthesia, and rash.
The following additional local adverse reactions are reported infrequently with topical corticosteroids, and they may occur more frequently with high potency corticosteroids, such as Halobetasol Propionate Ointment. These reactions are listed in an approximate decreasing order of occurrence: folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, striae and miliaria. Overdosage
Topically applied Halobetasol Propionate Ointment can be absorbed in sufficient amounts to produce systemic effects (see PRECAUTIONS).
Dosage and Administration Apply a thin layer of Halobetasol Propionate Ointment to the affected skin once or twice daily, as directed by your physician, and rub in gently and completely.
Halobetasol Propionate Ointment is a super-high potency topical corticosteroid; therefore, treatment  should be limited to two weeks, and amounts greater than 50 g/wk should not be used. As with
other corticosteroids, therapy should be discontinued when control is achieved. If no improvement is seen within 2 weeks, reassessment of diagnosis may be necessary.
Halobetasol Propionate Ointment should not be used with occlusive dressings. How Supplied Halonate™ is supplied in the following:
(NDC 68712-042-01) one 50 g tube of halobetasol propionate ointment 0.05% packaged with one
4 oz can of ammonium lactate mousse 12%
STORAGE: Store between 15°C and 30°C (59°F and 86°F).
Manufactured by:
G and W Laboratories, Inc.
South Plainfield, NJ  07080
Manufactured for:
Innocutis Holdings LLC
Charleston, SC  29401
1-800-499-4468
www.innocutis.com


Halonate PAC 
halobetasol   ointment Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 68712-042 Route of Administration TOPICAL DEA Schedule      Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength HALOBETASOL PROPIONATE (HALOBETASOL ) HALOBETASOL PROPIONATE 0.5 mg  in 1 g Inactive Ingredients Ingredient Name Strength ALUMINUM STEARATE   YELLOW WAX   PENTAERYTHRITOL   PETROLATUM   PROPYLENE GLYCOL   Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains          Packaging # NDC Package Description Multilevel Packaging 1 68712-042-01 50 g In 1 TUBE None
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA077721 05/01/2010
Labeler - Innocutis Holdings LLC (071501252) Establishment Name Address ID/FEI Operations G &W Laboratories Inc. 001271188 manufacture Revised: 11/2011Innocutis Holdings LLC More Halonate resources Halonate Side Effects (in more detail) Halonate Use in Pregnancy & Breastfeeding Halonate Drug Interactions Halonate Support Group 0 Reviews for Halonate - Add your own review/rating Halonate Ointment MedFacts Consumer Leaflet (Wolters Kluwer) Ultravate Pack Ointment Concise Consumer Information (Cerner Multum) Compare Halonate with other medications Atopic Dermatitis Dermatitis Eczema Psoriasis
read more


Sterile Talc



Prescribing Information
NDC 63256-200-05
Cat. # 1690

For Intrapleural Administration Only

Sterile Talc Description

Sterile Talc Powder is a sclerosing agent intended for intrapleural administration supplied in a single use 100 mL brown glass bottle, sealed with a gray, 20 mm stopper and covered with a flip-off seal. Each bottle contains a minimum of 5.0 g of Talc USP (Ultra 2000 Talc), either white or off-white to light gray, asbestos-free and brucite-free grade of talc of controlled particle size. The composition of the talc is ? 95% talc as hydrated magnesium silicate. The empirical formula of talc is Mg3 Si4 010 (OH)2 with a molecular weight of 379.3. Associated naturally occurring minerals include chlorite (hydrated aluminum and magnesium silicate.), dolomite (calcium and magnesium carbonate), calcite (calcium carbonate) and quartz. Talc is practically insoluble in water and in dilute solutions of acids and alkali hydroxides. The finished product has been sterilized by gamma irradiation.

Sterile Talc - Clinical Pharmacology Mechanism of Action

The therapeutic action of talc instilled into the pleural cavity is believed to result from induction of an inflammatory reaction. This reaction promotes adherence of the visceral and parietal pleura, obliterating the pleural space and preventing reaccumulation of pleural fluid.

The extent of systemic absorption of talc after intrapleural administration has not been adequately studied. Systemic exposure could be affected by the integrity of the pleural surface, and therefore could be increased if talc is administered immediately following lung resection or biopsy.

Clinical Studies

The data demonstrating safety and efficacy of talc slurry administered via chest tube for the treatment of patients with malignant pleural effusions are from the published medical literature. The following prospective, randomized studies were designed to evaluate the risk of recurrence of malignant pleural effusions in patients with a variety of solid tumors. The studies compared talc slurry, instilled into the pleural cavity via chest tube, versus a concurrent control. In all studies, after maximal drainage of the pleural effusion, the investigator administered talc slurry via chest tube. Chest films documented response (defined as lack of recurrence of fluid for a period of time). Studies differed on the timing of the efficacy assessment. Zimmer et al. did not specify the time required evaluations. Ong et al. specified the assessment at one month. Sorensen et al. specified the assessment at 3-4 months. The remaining studies assessed response at the completion of the follow-up period.

Randomized Controlled Trials Using Talc Slurry as a Sclerosing Agent

*   Two-sided p-value based on Fisher's exact test

a   Patients were evaluable if chest x-rays were done to assess response per protocol.

    The Sorensen study excluded patients if incomplete lung re-expansion was noted post drainage.

b   Data per procedure (33 procedures in 29 evaluable patients, 3 patients with bilateral effusions).

c   Plus lidocaine 1%, 20 mL.

d   Plus lidocaine 1%, 10 mL.

REFERENCE TREATMENT RESPONSE RATE EVALUABLE PTS*
p value* RESPONSE RATE ALL PTS*
p value* Sorensen et al.
Eur J Respir Dis. 1984:
65(2):131-5 Talc Slurry
10g /250ml NS
vs.
Chest tube drainage alone 100% (9/9)
vs.
58% (7/12)
p=0.04 64% (9/14)
vs.
41% (7/17)
p=0.29 Noppen et al.
Acta Clin Belg 1997; 52(4):258-62 Talc Slurry
5g/50-ml NS
vs.
Bleomycin 1mg/kg/50ml NS 79% (11/14)
vs.
75% (9/12)
p=1.00 79% (11/14)
vs.
75% (9/12)
p=1.00 Zimmer PW et al.
Chest 1997;
112(2):430-434 Talc Slurry
5g/50 ml NSc
vs.
Bleomycin 60U/50 ml NSc 90% (17/19b)
vs.
79% (11/14 b)
p=0.63
Not Given Ong KC et al. Respirology 2000;
5:99-103 Talc Slurry
5g/150ml NSd
vs.
Bleomycin 1U/kg/150 ml NSd 89% (16/18)
vs.
70% (14/20)
p=0.24 64% (16/25)
vs.
56% (14/25)
p=0.77 Yim AP et al.
Ann Thorax Surg 1996; 62:1655-8 Talc Slurry 5g/50ml NS, lidocaine 2% 10 ml
vs. Talc Insufflation 5g powder 90%(26/29)
vs.
96% (27/28)
p=0.61 90% (26/29)
vs.
96% (27/28)
p=0.61

In single-arm studies of malignant pleural effusions from the published literature, variously defined "success" rates using talc slurry pleurodesis ranged from 75% to 100%.

Indications and Usage for Sterile Talc

Sterile Talc Powder, administered intrapleurally via chest tube, is indicated as a sclerosing agent to decrease the recurrence of malignant pleural effusions in symptomatic patients.

Contraindications

None known

Warnings

None

Precautions

1.   Future procedures: The possibility of the future diagnostic and therapeutic procedures involving the hemithorax to be treated must be considered prior to administering Sterile Talc Powder. Sclerosis of the pleural space may preclude subsequent diagnostic procedures of the pleura on the treated side. Talc sclerosis may complicate or preclude future ipsilateral lung resective surgery, including pneumonectomy for transplantation purposes.

2.   Use in potentially curable disease: Talc has no known antineoplastic activity and should not be used alone for potentially curable malignancies where systemic therapy would be more appropriate, e.g., a malignant effusion secondary to a potentially curable lymphoma.

3.   Pulmonary complications: Acute Pneumonitis and Acute Respiratory Distress Syndrome (ARDS) have been reported in association with intrapleural talc administration. Three of the case reports of ARDS have occurred after treatment with a relatively large talc dose (10 g) administered via intrapleural chest tube instillation. One patient died one month post treatment and two patients recovered without further sequelae.

DRUG INTERACTIONS

It is not known whether the effectiveness of a second sclerosing agent after prior talc pleurodesis would be diminished by the absorptive properties of talc.

Carcinogenesis, Mutagenesis, Impairment of Fertility: Studies on the carcinogenicity of talc have been performed using non-standard designs which prevent firm conclusions on its carcinogenicity. With single intraperitoneal administration to mice at 20 mg and observation for at least 6 months or 4 weekly doses administered intraperitoneally at 25 mg/dose to rats with observation for at least 84 weeks, tumor incidence was not increased. In these studies the talc and its asbestos content were not characterized.

Genotoxicity was tested in cultures of rat pleural mesothelial cells (RPMC) as unscheduled DNA synthesis (UDS) and sister chromatid exchanges (SCEs). None of the talc samples (which were asbestos-free) induced enhancement of UDS or SCEs in treated cultures. No information is available on impairment of fertility in animals by talc.

Pregnancy: Pregnancy Category B. An oral administration study has been performed in the rabbit at 900 mg/kg. Approximately 5 fold higher than a human dose on mg/m2 basis, and has revealed no evidence of teratogenicity due to talc. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should not be used during pregnancy unless the benefit outweighs the risk.

Pediatric Use: The safety and efficacy of Sterile Talc Powder in pediatric patients have not been established.

Geriatric use: The estimated mean and median ages of patients treated with talc slurry from clinical studies (single-arm or randomized) were 60 and 62 years, respectively. No analyses to specifically evaluate the safety and efficacy in the geriatric population have been reported.

Adverse Reactions

Intrathoracic administration of talc slurry has been described in medical literature reports involving more that 2000 patients. Patients with malignant pleural effusions were treated with talc via poudrage or slurry. In general, with respect to reported adverse experiences, it is difficult to distinguish the effects of talc from the effects of the procedure(s) associated with its administration. The most often reported adverse experiences to intrapleurally-administered talc were fever and pain.

Infection: Complications reported include empyema.

Respiratory: Complications reported include hypoxemia, dyspnea, unilateral pulmonary edema, pneumonia, ARDS, brochopleural fistula, hemoptysis and pulmonary emboli.

Cardiovascular: Complications reported included tachycardia, myocardial infarction, hypotension, hypovolemia and asystolic arrest

Delivery Procedure: Adverse reactions due to the delivery procedure and the chest tube may include: pain, infection at the site of thoracostomy or thoracoscopy, localized bleeding, and subcutaneous emphysema.

Chronic Toxicity: Since patients in clinical studies had a limited life expectancy, data on chronic toxicity are limited

Overdosage

No definite relationship between dose and toxicity has been established. Excessive talc may be partially removed with saline lavage.

Sterile Talc Dosage and Administration

Sterile Talc Powder should be administered after adequate drainage of the effusion. The success of the pleurodesis appears to be related to the completeness of the drainage of the pleural fluid, as well as the full re-expansion of the lung, both of which will promote symphysis of the pleural surfaces.

The recommended dose is 5 g, dissolved in 50 - 100 ml Sodium Chloride Injection, USP.  Although the optimal dose for effective pleurodesis is unknown, 5 g was the dose most frequently reported in the published literature.

Talc Preparation

Prepare the talc slurry using aseptic technique in an appropriate laminar flow hood. Remove talc container from packaging. Remove protective flip-off seal.

Each brown bottle contains 5 g of Sterilized Talc Powder. To dispense the contents:

Using a 16 gauge needle attached to a 60-mL LuerLok syringe, measure and draw up 50 mL of Sodium Chloride Injection, USP.  Vent the talc bottle using a needle. Slowing inject the 50 mL of Sodium Chloride Injection, USP  into the bottle. For doses more than 5 g, repeat this procedure with a second bottle. Swirl the bottle(s) to disperse the talc powder and continue swirling to avoid settling of the talc in the slurry. Each bottle will contain 5 g Sterile Talc Powder dispersed in 50 mL of Sodium Chloride Injection, USP. Divide the content of each bottle into two 60 mL irrigation syringes by withdrawing 25 mL of the slurry into each syringe with continuous swirling. QS each syringe with Sodium Chloride Injection, USP  to a total volume of 50 mL in each syringe. Draw air into each syringe to the 60 mL mark to serve as a headspace for mixing prior to administration. When appropriately labeled, each syringe contains 2.5 g of Sterile Talc in 50 mL of Sodium Chloride Injection, USP  with an air headspace of 10 mL. Once the slurry has been made, use within 12 hours or discard and prepare fresh slurry. Label the syringes appropriately noting the expiration date and time, with the statement “For Pleurodesis Only – NOT FOR IV ADMINISTRATION,” the identity of the patient intended to receive this material and a cautionary statement to SHAKE WELL before use. Prior to administration, completely and continuously agitate the syringes to evenly redisperse the talc and avoid settlement. Immediately prior to administration, vent the 10mL air headspace from each syringe. Attach the adapter and place a syringe tip on the adapter. Maintain continuous agitation of the syringes.

NOTICE: Shake well before installation. Each 25 ml of prepared slurry in the syringe contains 1.25 g of talc. NOT FOR IV ADMINISTRATION.

Administration

Administer the talc slurry through the chest tube by gently applying pressure to syringe plunger and empty the contents of the syringe into the chest cavity. After application, discard the empty syringe according to general hospital procedures. After the talc slurry has been administered through the chest tube into the pleural cavity, the chest tube may be flushed with 10- 25 mL sodium chloride solution to ensure that the complete dose of talc is delivered.

Following introduction of the talc slurry, the chest drainage tube is clamped, and the patient is asked to move, at 20 to 30 minute intervals, from supine to alternating decubitus positions, so that over a period of about 2 hours the talc is distributed within the chest cavity. Recent evidence suggests that this step may not be necessary.

At the end of this period, the chest drainage tube is unclamped, and the excess saline is removed by the routine continual external suction on the tube.

How is Sterile Talc Supplied

NDC 63256-200-05 Sterile Talc Powder is supplied in a 100 mL brown glass bottle containing 5 g of talc. The sterile bottle is closed with a gray stopper and covered with a flip-off seal.

Storage: Store at Room Temperature (18-25°C). Protect against sunlight.

DISTRIBUTED BY: Bryan Corporation. Woburn, MA 01801

Version: Original Sep 2003


TALC 
talc  aerosol, powder Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 63256-200 Route of Administration INTRAPLEURAL DEA Schedule      INGREDIENTS Name (Active Moiety) Type Strength Talc (Talc) Active 5 GRAM  In 1 CANISTER Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains          Packaging # NDC Package Description Multilevel Packaging 1 63256-200-05 1 CANISTER In 1 CANISTER None
Revised: 10/2006Bryan Corporation More Sterile Talc resources Sterile Talc Side Effects (in more detail) Sterile Talc Support Group 0 Reviews · Be the first to review/rate this drug Sclerosol Monograph (AHFS DI)
read more


Sclerosol


sterile talc
Dosage Form: Powder

Prescribing Information

For Intrapleural Administration Only

Shake Well Immediately Before Using

Sclerosol Description

Sclerosol® Intrapleural Aerosol (sterile talc powder 4 g) is a sclerosing agent for intrapleural administration supplied as a single-use, pressurized spray canister with two delivery tubes of 15 cm and 25 cm in length. Each canister contains 4.0 g of talc, either white or off-white to light grey, asbestos-free, and brucite-free grade of talc of controlled granulometry. The composition of the talc is ? 95% talc as hydrated magnesium silicate. The empirical formula is Mg3 Si4 O10 (OH)2 with molecular weight of 379.3. Associated naturally occurring minerals include chlorite (hydrated aluminum and magnesium silicate), dolomite (calcium and magnesium carbonite), calcite (calcium carbonate) and quartz. Talc is practically insoluble in water, and in dilute solutions of acids and alkali hydroxides. The canister and delivery tubes have been sterilized by gamma irradiation. The aerosol propellant contained in Sclerosol® Intrapleural Aerosol is dichlorodifluoromethane (CFC-12) with 26 g present per canister. The canister delivers 0.4 g of talc per second through the valve and the product contains no other excipients.

Sclerosol - Clinical Pharmacology Mechanism of Action:

The therapeutic action of talc instilled into the pleural cavity is believed to result from induction of an inflammatory reaction. This reaction promotes adherence of the visceral to the parietal pleura, obliterating the pleural space and preventing reaccumulation of pleural fluid. The extent of talc systemically absorbed after intrapleural administration has not been adequately studied. Systemic exposure could be affected by the integrity of the visceral pleura, and therefore could be increased if talc is administered immediately following lung resection or biopsy.

Clinical Studies

The data demonstrating safety and efficacy of talc in the treatment of malignant pleural effusions are derived from the published medical literature. The following four trials were prospective, randomized studies of talc vs. a concurrent control, and provide sufficient detail for evaluation, including a clear, readily determined definition of response (no fluid reaccumulation by chest roentgenogram at one month or greater) and information allowing an analysis of all patients randomized. Talc was statistically significantly superior to the control arms in evaluable patients across the studies.

REFERENCE TREATMENT TUMOR RESPONSE RATE IN
EVALUABLE PTS
p value: Fisher's Exact* RESPONSE RATE IN
ALL PATIENTS
p value: Fisher's Exact* MINIMUM
DURATION OF
RESPONSE

*p values are two-sided

Sorenson et al.
Eur J Respir Dis.
1984; 65:131 Talc slurry
vs
Chest tube drainage Variety 100% (9/9)
vs
58% (7/12)
p=0.022 64% (9/14)
vs
41% (7/17)
p=0.285 3 months Fentiman et al .
Eur J Cancer Clin
Oncol 1986;
22:1079 Talc poudrage
vs
Tetracycline solution Breast 92% (11/12)
vs
48% (10/21)
p=0.022 61% (11/18)
vs
43% (10/23)
p=0.345 12 months Fentiman et al .
Cancer 1983;
52:737 Talc poudrage
vs
Mustine solution Breast 90% (18/20)
vs
53% (9/17)
p=0.023 78% (18/23)
vs
39% (9/23)
p=0.016 6 months Hamed et al .
Br. J. Surg
1989; 76:1266 Talc poudrage
vs
Bleomycin solution Breast 100% (10/10 procedures)
vs
33% (5/15 procedures)
p=0.001 (unclear; results reported as procedures, not patients) ?1 months

In other studies, greater than 1000 patients with malignant pleural effusions have been reported (with varying degrees of detail and durations of response) to have had successful pleurodesis with talc.

Indications and Usage for Sclerosol

Sclerosol® Intrapleural Aerosol, administered by aerosol during thoracoscopy or open thoracotomy, is indicated to prevent recurrence of malignant pleural effusions in symptomatic patients.

Contraindications

None known.

Warnings

None.

Precautions General:

        1)Future procedures. The possibility of future diagnostic and therapeutic procedures involving the hemithorax to be treated must be considered prior to administering Sclerosol® Intrapleural Aerosol. Sclerosis of the pleural space may preclude subsequent diagnostic procedures of the pleura on the treated side. Talc sclerosis may complicate or preclude future ipsilateral lung resective surgery, including pneumonectomy for transplantation purposes.

        2)Use in potentially curable disease. Talc has no known antineoplastic activity and should not be used for potentially curable malignancies where systemic therapy would be more appropriate, e.g., a malignant effusion secondary to a potentially curable lymphoma.

        3)Potential pulmonary complications. Acute pneumonitis or acute respiratory distress syndrome (ARDS) have rarely been reported in association with intrapleural talc administration. Whether these were causally related to talc is unclear. In none of the reported cases was talc applied thoracoscopically or by insufflation. Three of four case reports of ARDS have occurred after treatment with 10 g of talc administered via intrapleural chest tube instillation. One patient died one month post treatment and two patients recovered without further sequelae.

Intravenous administration of talc is a well-recognized cause of pulmonary hypertension and pulmonary lung parenchymal disease, but these complications have not been reported after intrapleural administration. Pulmonary diseases, e.g., silicosis or asbestosis-like diseases, chronic bronchitis, bronchogenic carcinoma, and pleural plaques have been reported in association with inhaled talc.

        4)Contents under pressure. The contents of the Sclerosol® Intrapleural Aerosol (sterile talc powder) canister are under pressure. The canister must not be punctured and should not be used or stored near heat or open flame.

Drug Interactions: It is not known whether the effectiveness of a second sclerosing agent after prior talc pleurodesis would be diminished by the absorptive properties of talc.

Carcinogenesis, Mutagenesis, Impairment of Fertility: Studies on the carcinogenicity of talc have been performed using non-standard designs, which prevent firm conclusions on its carcinogenicity. With single intraperitoneal administration to mice at 20 mg and observation for at least 6 months, or 4 weekly doses administered intraperitoneally at 25 mg/dose to rats with observation for at least 84 weeks, tumor incidence was not increased. In these studies, the talc and its asbestos content were not characterized. Genotoxicity was assessed in cultures of rat pleural mesothelial cells (RPMC), as unscheduled DNA syntheses (UDS) and sister chromatid exchanges (SCEs). None of the talc samples (which were asbestos free) enhanced UDS or SCEs in treated cultures. No information is available on impairment of fertility in animals by talc.

Pregnancy: Pregnancy category B. An oral administration study has been performed in the rabbit at 900 mg/kg, approximately 5-fold higher than the human dose on mg/m2 basis, and has revealed no evidence of teratogenicity due to talc. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should not be used during pregnancy unless it is clearly needed.

Pediatric Use: The safety and efficacy of Sclerosol Intrapleural Aerosol® (sterile talc powder) in pediatric patients have not been established.

Geriatric Use: The mean and median ages of patients treated with talc in the clinical studies table were 50-62 years. No analyses to specifically evaluate the safety and efficacy in the geriatric population have been reported.

Adverse Reactions

Talc administration has been described in more than 1500 patients reported in the medical literature. Patients with malignant pleural effusions were treated with talc via poudrage or slurry. In general, with respect to reported adverse experiences, it is difficult to distinguish the effects of talc from the effects of the procedure(s) associated with its administration. The most reported common adverse experiences were fever and pain. Almost all of the cases of fever, and over half of the cases of pain, were in patients who received diagnostic biopsies at the time of talc administration.

Infections: Empyema was a rare complication of talc administration and/or the procedure. Biopsies had been obtained prior to onset in over half the reported cases.

Respiratory: Rare instances of pneumonia, ARDS, dyspnea, bronchopleural fistula, hemoptysis, and pulmonary emboli have been reported.

Cardiovascular: Tachycardia, myocardial infarction, hypotension, hypovolemia, and asystolic arrest associated with surgery and/or anesthesia have been rarely reported.

Delivery Procedure: Adverse reactions due to the delivery procedure and the chest tube may include: infection at the site of thoracostomy or thoracoscopy, localized bleeding, and subcutaneous emphysema.

Chronic Toxicity: Lange et al. (Thorax 1988;43:559) reported on 114 consecutive cases of idiopathic spontaneous pneumothorax treated with talc poudrage (60 patients), or simple drainage (54 patients) via an intercostal tube. Pulmonary function tests (FEV1, VC, TLC, and RV) 22 go 35 years after treatment, showed no significant differences in the incidence of pleural changes between the two groups. Two patients treated with talc poudrage had more extensive pleural thickening with calcification. The mean total lung capacities were 89% of predicted in the talc group and 96% in the drainage only group. Fourteen patients (12 lifelong heavy smokers, 2 non-smokers) had airflow limitation (5 severe). Source and purity of the talc used was not reported. No cases of mesothelioma were reported. One case report noted the occurrence of adenocarcinoma of the chest wall two years after pleurodesis following 10 g of 1% iodized talc (administered for recurrent pneumothorax).

Overdosage

Overdosages have not been reported. See PRECAUTIONS: 3) Potential pulmonary complications.

Sclerosol Dosage and Administration

Sclerosol® Intrapleural Aerosol (sterile talc powder) is administered after adequate drainage of the effusion. It has been suggested that success of the pleurodesis is related to the completeness of the drainage of the pleural fluid, as well as full reexpansion of the lung, both of which will promote symphysis of the pleural surfaces.

The usual dosage of Sclerosol® Intrapleural Aerosol (sterile talc powder) is a single 4-8 g dose delivered intrapleurally from the spray canister (1-2 cans), which delivers talc at a rate of 0.4 g per second.

ADMINISTRATION PROCEDURE

Shake canister will before usage. Remove protective cap and securely attach actuator button with its delivery tube (either 15 cm or 25 cm) to the valve stem of canister.

Insert delivery tube through pleural trocar, taking care not to place the distal end of the delivery tube adjacent to the lung parenchyma or directly against the chest wall. While firmly holding the delivery tube and pleural trocar together in one hand, gently apply pressure to the actuator button on the canister. Sclerosol Intrapleural Aerosol® is not delivered by metered dose, but depends on the extent and duration of manual compression of the actuator button on the canister. The distal end of the delivery tube should be pointed in several different directions, while short bursts are administered in order to distribute the talc powder equally and extensively on all visceral and parietal pleural surfaces. For optimal distribution, always maintain the Sclerosol Intrapleural Aerosol® (sterile talc powder) canister in the upright position. After application, discard the canister and delivery tube. The duration of chest tube drainage following talc sclerosis is dictated by the clinical situation.

How is Sclerosol Supplied

NDC 63256-100-30: Sclerosol® Intrapleural Aerosol (sterile talc powder) contains 4.0 g of talc suspended in 26 g of inert propellant in a single-use aluminum canister. The canister if fitted with a continuous spray valve which delivers approximately 0.4 g of talc per second. This canister, attached to an actuator button, and two delivery tubes of 15 cm and 25 cm length, are supplied in a sterile, flexible plastic peel pack.

STORAGE: Warning: Contents under pressure. Do not puncture or incinerate container. Store between 59°F - 86°F (15°C - 30°C). Protect against sunlight and do not expose to a temperature above 120° F (49° C), or the canister may rupture. Avoid freezing. Shake well before using.

NOTE: The indented statement below is required by the Federal Government's Clean Air Act for all products containing or manufactured with chlorofluorocarbons (CFCs).

Warning: Contains CFC-12, a substance which harms public health and environment by destroying ozone in the upper atmosphere.

DISTRIBUTED BY: Bryan Corporation, Woburn MA 01801


Sclerosol 
talc  aerosol, powder Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 63256-100 Route of Administration INTRAPLEURAL DEA Schedule      INGREDIENTS Name (Active Moiety) Type Strength Talc (Talc) Active 4.0 GRAM  In 1 CANISTER Dichlorodifluromethane (CFC-12) Inactive   Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains          Packaging # NDC Package Description Multilevel Packaging 1 63256-100-30 1 CANISTER In 1 CANISTER None
Revised: 10/2006Bryan Corporation More Sclerosol resources Sclerosol Side Effects (in more detail) Sclerosol Support Group 0 Reviews · Be the first to review/rate this drug Sclerosol Monograph (AHFS DI)
read more


Indivina


Indivina 1 mg/2.5 mg tablets

Indivina 1 mg/5 mg tablets

Indivina 2 mg/5 mg tablets

estradiol /medroxyprogesterone

Read all of this leaflet carefully before you start taking this medicine Keep this leaflet. You may need to read it again. If you have any further questions, ask your doctor or pharmacist. This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours. If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist. In this leaflet:

1. What Indivina is and what it is used for
2. Before you take Indivina
3. How to take Indivina
4. Possible side effects of Indivina
5. How to store Indivina
6. Further information

What Indivina Is And What It Is Used For

The name of your medicine is Indivina. It is a hormone replacement therapy (HRT) used to treat some of the symptoms which occur when the oestrogen levels decline and the periods stop (menopause) by replacing the oestrogen that your body is no longer producing. The tablets contain oestrogen and progestogen. Indivina is only recommended for women whose periods stopped more than three years ago and who still have their womb.

Indivina can also be used to help to prevent osteoporosis (thinning of the bones) if you are at an increased risk of fractures due to osteoporosis but are unable to take other treatments or if other therapies prove to be ineffective. Your doctor should discuss all the available options with you.

There is only limited experience of treating women older than 65 years with Indivina.

Before You Take Indivina Medical check-ups

Before you start taking Indivina, your doctor will inform you about the risks and benefits of the treatment (see also section 4, “Other side effects of combined HRT”). Before you start treatment and regularly during treatment, your doctor will evaluate whether Indivina is the right treatment for you. Your doctor will tell you how often you should go for periodic check-ups, taking into account your general state of health. If you have any close relative (mother, sister, maternal or paternal grandmother), who has suffered from serious illness, e.g. blood clot or breast cancer, you might be at increased risk. You should therefore always tell your doctor about any close relative suffering from serious illness, and you should also tell your doctor about any changes, you might find in your breasts.

As well as regular check-ups with your doctor, be sure to:

Regularly check your breasts for any changes, such as dimpling or sinking of the skin, changes in the nipple, or any lumps you can see or feel. Go for regular breast screening (mammography) and cervical smear tests. While you are receiving this medication, you should see your doctor regularly, at least every six to twelve months If you have unusual symptoms such as unexplained pains in the chest, abdomen or legs you must consult your doctor immediately. If you have a family history of breast cancer you should use this medication with great caution. Do not take Indivina, if: you are allergic (hypersensitive) to estradiol valerate or medroxyprogesterone acetate or any of the other ingredients of Indivina (see section 6: Further information) you have or have had breast cancer in the past you have or have had an oestrogen-dependent tumour such as endometrial cancer (cancer of the lining of the womb) you have unusual vaginal bleeding that has not been checked by a doctor you have endometrial hyperplasia (abnormal growth of the lining of the womb) that is not being treated you have had a recent blood clot of an artery (leading to chest pain or heart attack) you have had liver disease and have been told by your doctor that your liver function has not yet returned to normal you have or have had a blood clot in a vein in your leg or anywhere else (a “deep vein thrombosis or pulmonary embolism”) you have porphyria (a genetic disorder). Take special care with Indivina

As well as benefits, HRT has some risks which you need to consider when you are deciding whether to take it, or whether to carry on taking it. Tell your doctor if you have any of the following as you may need more frequent check ups’ if:

you think you might be at risk of oestrogen dependent tumors such as breast cancer or endometrial cancer (see the section below on effects on your risk of developing cancer) you have had endometrial hyperplasia (thickening of the lining of the womb) you have uterine fibroids or endometriosis you feel you might be at risk of developing blood clots (see section below on blood clots) you have liver, kidney or heart problems you have gallstones you have asthma, epilepsy or diabetes you have high blood pressure you have otosclerosis (hearing problems due to bone overgrowth in the ear) you have been told that you have an intolerance to some sugars you have systemic lupus erythematosus (SLE) you have migraine or severe headaches you have been told you have high cholesterol or fat levels in your blood you are going to have surgery, make sure your doctor knows about it. You may need to stop taking HRT about 4 to 6 weeks before the operation, to reduce the risk of a blood clot. Your doctor will tell you when you can start taking HRT again.

HRT may change the results of some laboratory tests. If you are going to have any laboratory tests, tell your doctor/nurse that you are taking Indivina.

Taking other medicines

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

In particular tell your doctor if you are taking any of the following:

antibiotics such as rifampicin, rifabutin anti-epileptic medicines such as phenytoin, phenobarbital and carbamazepine HIV medicines such as nelfinavir, ritonavir, nevirapine and efavirenz the herbal preparation St. Johns Wort.

If you are in any doubt about taking other medicines with Indivina, talk to your doctor or your pharmacist.

Taking Indivina with food and drink

Indivina can be swallowed with a glass of water at the same time each day.

Pregnancy and breast-feeding Pregnancy – Do not take Indivina if you are pregnant, think you are pregnant or planning to become pregnant Breast feeding – Do not take Indivina if you are breast feeding.

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

Indivina should not affect your ability to drive or operate machinery.

Important information about some ingredients of Indivina

This medicine contains lactose. If you have been told by your doctor that you have intolerance to some sugars, contact your doctor before taking this medicinal product.

How To Take Indivina

Always take Indivina as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.

Take one Indivina tablet every day, preferably at about the same time each day. Calendar days are printed on the blister sheet to help you follow your daily tablet intake. Swallow the tablet whole with a drink if necessary. You will normally start on the lowest dose of Indivina and this will be increased, if necessary. Your doctor should aim to prescribe the lowest dose for the shortest time that gives you relief from your symptoms. Talk to your doctor if your symptoms are not better after three months. If you feel that the effect of Indivina is too strong or too weak, do not change the dose or stop taking the tablets yourself, but ask your doctor for advice.

If you are not having periods and you have not previously taken HRT or you are changing from another continuous combined HRT product, treatment with Indivina may be started on any day.

If you switch from a cyclic HRT regimen, start Indivina treatment one week after taking the last tablet of the cyclic HRT. Talk to your doctor or pharmacist if you are unsure.

Whilst taking this medicine

When you first start taking Indivina you may get some bleeding at odd times for a few months (Please also refer to the section above on Endometrial cancer). However, if this is still happening after a few months or if you experience heavy bleeding tell your doctor.

If you take more Indivina than you should:

If you or somebody else has taken too many Indivina tablets, talk to your doctor or pharmacist. An overdose of Indivina could make you feel sick or make you get a headache or uterine bleeding.

If you forget to take Indivina:

It is best to take the tablet at the same time each day. If you forget to take a tablet leave the forgotten tablet. You should then continue by taking the next tablet at your usual time. Missing a tablet or irregular use of Indivina tablets may cause breakthrough bleeding or spotting.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

If you stop taking Indivina

If you want to stop taking Indivina, talk to your doctor first. He/she will explain the effects of stopping treatment and discuss other possibilities with you.

Indivina Side Effects

Like all medicines, Indivina may cause side effects although not everybody gets them, particularly early on (in the first few months of treatment), for example irregular bleeding may occur. These often disappear with continued treatment.

There are a number of situations in which you may have to stop taking Indivina. Tell your doctor immediately if you develop any of the following conditions:

Common (affecting more than 1 person in 100):

feeling sick, stomach pain headache breast tenderness, breast enlargement, breakthrough bleeding weight increase or decrease changes in mood including anxiety and depressive mood, changes in libido increase in size of uterine muscle lumps (fibroids) swelling caused by fluid retention

Uncommon (affecting more than 1 in 1,000 but less than 1 in 100)

dizziness, migraine leg cramps increased blood pressure vaginal thrush (candidiasis) indigestion/heartburn wind, vomiting gall bladder disease and/or gallstones

Rare (affecting more than 1 in 10,000 but less than 1 in 1,000)

skin rash, itching blood clots hair loss, excessive hair growth (hirsutism) Other side effects of combined HRT

The following side effects have been reported after taking other oestrogen/progestagen products:

Oestrogen dependent tumours, heart attack, stroke, disorders of skin and underlying tissues.

Endometrial hyperplasia and endometrial cancer

In women with an intact uterus, the risk of excessive growth of the womb lining (endometrial hyperplasia) is increased. Treatment with unopposed oestrogens for long periods of time increases the risk of cancer of the lining of the womb (endometrial cancer). Adding a progestagen, which Indivina contains, greatly reduces this increased risk.

Compare

Looking at women who still have a uterus and who are not taking HRT, on average, 5 in 1000 will be diagnosed with endometrial cancer between the ages of 50 and 65. For women who take oestrogen-only HRT the number will be 2 to 12 times higher, depending on the dose and how long you take it. The addition of progestogen to oestrogen-only HRT substantially reduces the risk of endometrial cancer.

Breast cancer

Every woman is at risk of getting breast cancer whether or not she takes HRT. There is a small increase in this risk for women who have been using HRT compared with women of the same age who have never used HRT. This risk increases with the duration of intake of HRT, but returns to normal within a few (at most five) years of having stopped HRT. The risk seems to be higher for women who use oestrogen in combination with progestagen as compared to oestrogen alone.

Compare:

Looking at women aged 50 who are not taking HRT – on average, 32 in 1000 will be diagnosed with breast cancer by the time they reach the age of 65.

For women who start taking oestrogen-only HRT at age 50 and take it for 5 years, the figure will be between 33 and 34 in 1000 (i.e. an extra 1-2 cases).

If they take oestrogen-only HRT for 10 years, the figure will be, 37 in 1000 (i.e. an extra 5 cases). For women who start taking oestrogen plus progestogen HRT at age 50 and take it for 5 years, the figure will be 38 in 1000 (i.e. an extra 6 cases).

If they take oestrogen plus progestogen HRT for 10 years, the figure will be 51 in 1000 (i.e. an extra 19 cases).

To be able to detect a breast tumour as early as possible, it’s important to regularly check your breasts for any changes and to discuss any changes with your doctor. Also go for regular health check, including mammography. If you are anxious about the risk of developing breast cancer, you should talk to your doctor about the risks and benefits of hormone replacement therapy.

Blood clots in the deep veins

Every woman is at risk of getting a blood clot whether or not she takes HRT.

HRT may increase the risk of blood clots in the veins up to3 times, especially in the first year of taking it.

If you suspect you are suffering from a blood clot, seek immediate medical attention.

You are also more likely to get a blood clot:

If you are very overweight If you have had a blood clot before, or have had any blood clotting problem that needs treatment with a medicine such as Warfarin If any of your close family has had blood clots If you have had a miscarriage If you are off your feet for a long time through surgery, injury or illness If you have Systemic Lupus Erythematosus ((SLE) – an autoimmune disease)

Compare

Looking at women in their 50’s who are not taking HRT – on average, over a 5 year period, 3 in 1000 would be expected to get a blood clot.

For women in their 50s who are taking HRT, the figure would be 7 in 1000.

Looking at women in their 60s who are not taking HRT – on average, over a 5 year period, 8 in 1000 would be expected to get a blood clot.

For women in their 60’s who are taking HRT, the figure would be 17 in 1000.

Symptoms that may be indicative of blood clots:

Pain and swelling in your leg Sudden chest pain Difficulty breathing.

Seek immediate medical help. Stop taking HRT until your doctor says you can.

Heart disease

If you ever have had angina or heart attack, you should talk to your doctor about the risks and benefits of hormone replacement therapy.

There is no evidence from clinical trials of beneficial effects on the risks of cardiovascular disease with hormone replacement therapy in the menopause. Results from two large clinical studies showed that women, who used another type of oestrogen/progestagen combination, had a slightly increased risk of heart disease in the first year of use.

For other HRT products there are only very limited data from trials examining the effects on the risk of cardiovascular disease.

Stroke

There may be a slightly higher chance of having a stroke if you are taking HRT.

Other things that also increase the risk of stroke are:

Getting older High blood pressure Smoking Drinking too much alcohol An irregular heartbeat.

Compare

Looking at women in their 50’s who are not taking HRT - on average, over a 5 year period, 3 in 1000 would be expected to have a stroke.

For women in their 50s who are taking HRT, the figure would be 4 in 1000.

Looking at women in their 60s who are not taking HRT - on average, over a 5 year period, 11 in 1000 would be expected to have a stroke.

For women in their 60’s who are taking HRT, the figure would be 15 in 1000.

If you get:

Unexplained migraine-type headaches, with or without disturbed vision.

See a doctor as soon as possible. Stop taking HRT until your doctor says you can.

Ovarian cancer

Long-term (at least 5 or 10 years) use of oestrogen-only HRTs and oestrogen plus progestogen HRTs has been associated with an increased risk of ovarian cancer in some epidemiological studies.

Dementia

HRT will not prevent memory loss. In one study of women who started using combined HRT after the age of 65, a small increase in the risk of dementia was observed.

Effects on the skin

Brown patches in the face (chloasma), skin rashes including red inflammation on the hands or the legs (erythema multiforme), formation of tender, red nodules on the front of the legs/knees (erythema nodosum) or a bruise-like rash (vascular purpura).

If you notice any side effects not listed in this leaflet or if any of the side effects mentioned gets serious please tell your doctor or pharmacist.

How To Store Indivina

Keep out of the reach and sight of children. Do not use Indivina after the expiry date which is stated on the pack. Do not store above 30 ?C. Store in the original package in order to protect from moisture. Medicines should not be disposed via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

Further Information What Indivina contains:

The active ingredients of Indivina tablets are estradiol valerate and medroxyprogesterone acetate. Three different strengths of tablets are available.

Indivina 1 mg/2.5 mg tablets contain 1 mg of estradiol valerate and 2.5 mg medroxyprogesterone acetate.

Indivina 1 mg/5 mg tablets contain 1 mg of estradiol valerate and 5 mg medroxyprogesterone acetate.

Indivina 2 mg/5 mg tablets contain 2 mg of estradiol valerate and 5 mg medroxyprogesterone acetate.

The other ingredients of all Indivina tablets are lactose monohydrate, maize starch, gelatin, and magnesium stearate

What Indivina looks like and contents of the pack:

Indivina 1 mg/2.5 mg tablets are white, round, bevelled-edge, diameter 7 mm, flat tablets with a code ‘1 + 2.5’on one side.

Indivina 1 mg/5 mg tablets are white, round, bevelled-edge, diameter 7 mm, flat tablets with a code ‘1 + 5’on one side.

Indivina 2 mg/5 mg tablets are white, round, bevelled-edge, diameter 7 mm, flat tablets with a code ‘2 + 5’on one side.

The tablets are packed in a PVC/PVDC-aluminium blister of 28 tablets. The pack sizes available are 1 x 28 tablets and 3 x 28 tablets for all three strengths. All pack sizes may not be available in your country.

Marketing Authorisation Holder: Orion Corporation Orionintie 1 FIN-02200 Espoo FINLAND Manufactured by: Orion Corporation Tengstr?minkatu 8 FIN-20360 Turku FINLAND

This medicinal product is authorised in the Member States of the EEA under the following names:

Indivina, Duova

This leaflet was last revised: June 2010


read more


Cyclo-Progynova 2mg


Cyclo-Progynova 2 mg

Please read this leaflet carefully before you start to take your medicine. This leaflet provides a summary of the information known about your medicine. If you have any questions or are not sure about anything, ask your doctor or pharmacist.

Remember this medicine is for you. Only a doctor can prescribe this medicine and it may harm someone else, even if their symptoms are the same as yours.

About your medicine What is your medicine?

The name of your medicine is Cyclo-Progynova 2 mg.

Each strip of Cyclo-Progynova 2 mg has 11 white tablets containing 2 mg estradiol valerate and 10 pale brown tablets each containing 2 mg estradiol valerate and 500 micrograms of norgestrel.

The active ingredient in this medicine is estradiol. This is the new name for oestradiol. The ingredient itself has not changed.

Cyclo-Progynova 2 mg also contains the following inactive ingredients: lactose, maize starch, povidone, magnesium stearate (E 572), sucrose, polyethylene glycol 6000, calcium carbonate (E 170), glycerin (E 422), talc, montan glycol wax, titanium dioxide (E 171), yellow and red/brown ferric oxide pigments (E 172).

Each pack of Cyclo-Progynova 2 mg contains 1 or 3 memo-packs (strips) of 21 tablets.

Who produces your medicine The product licence is held by: MEDA Pharmaceuticals Ltd Skyway House Parsonage Road Takeley Bishop’s Stortford CM22 6PU This product is manufactured by: Bayer Schering Pharma AG D-13342 Berlin GERMANY What your medicine does and what it is used for

Cyclo-Progynova 2 mg is a hormone replacement therapy that contains the female sex hormones oestrogen and progestogen.

These hormones are lost in women during the "change of life" (also known as "the climacteric"). This is a gradual process which usually takes place between the ages of about 45 and 55. Periods usually become irregular, both in timing and amount of blood loss, before they stop altogether, but the time at which the periods finally stop - "the menopause" – is not the end of the change of life, which always continues for some time afterwards.

Although the change of life is natural, it often causes distressing symptoms such as hot flushes. These symptoms are due to the gradual loss of the female sex hormones produced by the ovaries.

Cyclo-Progynova 2 mg is used to treat symptoms associated with "the change of life".

In addition, the loss of these hormones may, in some women, lead to thinning of the bones (osteoporosis) in later life. If you are likely to develop osteoporosis, and are unable to take other medicines which can prevent osteoporosis, you may be prescribed Cyclo-Progynova 2 mg to prevent osteoporosis. Your doctor will be able to advise you further.

Cyclo-Progynova 2 mg will not make you able to have children, but on the other hand Cyclo-Progynova 2 mg will not prevent you becoming pregnant if you are still fertile.

Before taking your medicine You must not take Cyclo-Progynova 2 mg If you have, or have had, cancer of the breast If you have, or have had, cancer of the or womb If you currently have any problems with your liver If you have vaginal bleeding and the cause is not known If you have a condition called endometrial hyperplasia (where the lining of the womb grows more than normal) and if you are not having treatment for it If you have a blood clot in a vein in your leg or anywhere else (a "deep vein thrombosis") or if you have had one of these in the past If you have a blood clot that has travelled to your lung or another part of the body (an "embolus") or if you have had one of these in the past If you have, or have had, a disease related to blood clots such as angina, or a heart attack If you are allergic to any of the ingredients in Cyclo-Progynova If you have the condition known as porphyria. If you are pregnant, suspect that you are pregnant or if you are breast feeding What you should know before using Cyclo-Progynova

As well as benefits, HRT has some risks which you need to consider when you’re deciding whether to take it, or whether to carry on taking it.

Medical Check-ups

Before starting to take hormone replacement therapy you should discuss your personal and family medical history with your doctor.

Your doctor may decide to perform a physical examination of the breasts and/or a pelvic examination before starting this medication - but only if these examinations are necessary for you, or if you have any special concerns.

Once you’ve started on HRT, you should see your doctor for regular check-ups (at least once a year). At these check-ups, your doctor may discuss with you the benefits and risks of continuing to take HRT.

Before starting to take your medicine you must tell your doctor if you have, or have had any of the following as he may decide to alter your treatment or he may ask to see you more often:-

fibroids in your uterus endometriosis (when the lining of the womb grows outside the womb) a family history of cancer of the breast or womb liver disease diabetes gall stones migraine or severe headaches a condition known as systemic lupus erythematosus a condition called endometrial hyperplasia (where the lining of the womb grows more than normal) epilepsy asthma deafness (otosclerosis) hypertension risk factors that indicate you may experience blood clots. These include being seriously overweight, having blood clotting problems or having a blood clot previously. The full list of these risk factors is provided in the section on Blood clotting below.

Be sure to:

go for regular breast screening and cervical smear tests regularly check your breasts for any changes such as dimpling of the skin, changes in the nipple, or any lumps you can see or feel.

Effects On Your Heart or Circulation

Heart Disease

HRT is not recommended for women who have heart disease, or have had heart disease recently. If you have ever had heart disease, talk to your doctor to see if you should be taking HRT.

HRT will not help to prevent heart disease.

Studies with one type of HRT (containing conjugated oestrogen plus the progestogen MPA) have shown that women may be slightly more likely to get heart disease during the first year of taking the medication.

For other types of HRT, the risk is likely to be similar, although this is not yet certain.

If you get: a pain in your chest that spreads to your arm or neck you must see a doctor as soon as possible. Do not take any more HRT until your doctor says you can. This pain could be a sign of heart disease.

Stroke

Recent research suggests that HRT slightly increases the risk of having a stroke. Other things that can increase the risk of stroke include:

getting older high blood pressure smoking drinking too much alcohol an irregular heartbeat

If you are worried about any of these things, or if you have had a stroke in the past, talk to your doctor to see if you should take HRT.

Consider the following:

Looking at women in their 50s who are not taking HRT — on average, over a 5-year period, 3 in 1000 would be expected to have a stroke.

For women in their 50s who are taking HRT, the figure would be 4 in 1000.

Looking at women in their 60s who are not taking HRT — on average, over a 5-year period, 11 in 1000 would be expected to have a stroke.

For women in their 60s who are taking HRT, the figure would be 15 in 1000.

If you get unexplained migraine-type headaches (with or without disturbed vision) you must see a doctor as soon as possible. Do not take any more HRT until your doctor says you can. These headaches may be an early warning sign of a stroke.

Blood Clots

HRT may increase the risk of blood clots in the veins (also called deep vein thrombosis, or DVT), especially during the first year of taking it.

These blood clots are not always serious, but if one travels to the lungs, it can cause chest pain, breathlessness, collapse or even death. This condition is called pulmonary embolism, or PE.

DVT and PE are examples of a condition called venous thromboembolism, or VTE.

You are more likely to get a blood clot:

if you are seriously overweight if you have had a blood clot before if any of your close family have had blood clots if you have had one or more miscarriages if you have any blood clotting problem that needs treatment with a medicine such as warfarin if you’re off your feet for a long time because of major surgery, injury or illness if you have a rare condition called SLE

If any of these things apply to you, talk to your doctor to see if you should take HRT.

Consider the following:

Looking at women in their 50s who are not taking HRT — on average, over a 5-year period, 3 in 1000 would be expected to get a blood clot.

For women in their 50s who are taking HRT, the figure would be 7 in 1000.

Looking at women in their 60s who are not taking HRT — on average, over a 5-year period, 8 in 1000 would be expected to get a blood clot.

For women in their 60s who are taking HRT, the figure would be 17 in 1000.

If you get any of the following:

painful swelling in your leg sudden chest pain difficulty breathing

you must see a doctor as soon as possible. Do not take any more HRT until your doctor says you can. These may be signs of a blood clot.

If you’re going to have surgery, make sure your doctor knows about it. You may need to stop taking HRT about 4 to 6 weeks before the operation, to reduce the risk of a blood clot. Your doctor will tell you when you can start taking HRT again.

Effects on Your Risk of Developing Cancer

Breast Cancer

Women who have breast cancer, or have had breast cancer in the past, should not take HRT

Taking HRT slightly increases the risk of breast cancer; so does having a later menopause. The risk for a post-menopausal woman taking oestrogen-only HRT for 5 years is about the same as for a woman of the same age who’s still having periods over that time and not taking HRT. The risk for a woman who is taking oestrogen plus progestogen HRT is higher than for oestrogen-only HRT (but oestrogen plus progestogen HRT is beneficial for the endometrium, see ‘Endometrial cancer’ below).

For all kinds of HRT, the extra risk of breast cancer goes up the longer you take it, but returns to normal within about 5 years after stopping HRT. Your risk of breast cancer is also higher:

if you have a close relative (mother, sister or grandmother) who has had breast cancer if you are seriously overweight

Consider the following:

Looking at women aged 50 who are not taking HRT – on average 32 in 1000 will have breast cancer diagnosed by the age of 65.

For women who start taking oestrogen-only HRT at age 50 and take it for 5 years, the figure will be between 33 and 34 in 1000 (ie an extra 1-2 cases). If they take oestrogen-only HRT for 10 years, the figure will be 37 in 1000 (i.e. an extra 5 cases).

For women who start taking oestrogen plus progestogen HRT at age 50 and take it for 5 years, the figure will be 38 in 1000 (ie an extra 6 cases). If they take oestrogen plus progestogen HRT for 10 years, the figure will be 51 in 1000 (i.e. an extra 19 cases).

If you notice any changes in your breast, such as:

dimpling of the skin changes in the nipple any lumps you can see or feel

you must make an appointment to see your doctor as soon as possible.

Endometrial cancer (cancer of the lining of the womb)

Taking oestrogen-only HRT for a long time can increase the risk of cancer of the lining of the womb (the endometrium). Taking a progestogen as well as the oestrogen helps to lower the extra risk.

If you still have your womb, your doctor may prescribe a progestogen as well as oestrogen. If so, these may be prescribed separately, or as a combined HRT product.

If you have had your womb removed (a hysterectomy), your doctor will discuss with you whether you can safely take oestrogen without a progestogen.

If you’ve had your womb removed because of endometriosis, any endometrium left in your body may be at risk. If so, your doctor may prescribe HRT that includes a progestogen as well as an oestrogen.

Your product, Cyclo-Progynova 2 mg contains a progestogen.

Consider the following:

Looking at women who still have a uterus and who are not taking HRT – on average 5 in 1000 will be diagnosed with endometrial cancer between the ages of 50 and 65.

For women who take oestrogen-only HRT, the number will be 2 to 12 times higher, depending on the dose and how long you take it.

The addition of a progestogen to oestrogen-only HRT substantially reduces the risk of endometrial cancer.

If you get breakthrough bleeding or spotting, it’s usually nothing to worry about, especially during the first few months of taking HRT.

But if the bleeding or spotting:

carries on for more than the first few months starts after you’ve been on HRT for a while carries on even after you’ve stopped taking HRT

you must make an appointment to see your doctor. It could be a sign that your endometrium has become thicker.

Ovarian cancer

Ovarian cancer (cancer of the ovaries) is very rare, but it is serious.

It can be difficult to diagnose, because there are often no obvious signs of the disease.

Some studies have indicated that taking oestrogen-only HRT for more than 5 years may increase the risk of ovarian cancer. It is not yet known whether other kinds of HRT increase the risk in the same way.

What about other medicines that you may be taking?

Some medicines affect the way that drugs are handled by the liver and may reduce the effectiveness of Cyclo-Progynova 2 mg. These include some epilepsy medicines (for example phenytoin, phenobarbital and carbamazepine), and some antibiotics/anti-infectives (for example rifampicin, rifabutin, nevirapine, efavirenz, ritonavir, nelfinavir) and the herbal preparation, St John’s Wort.

If you are taking oral contraceptives, these should be stopped and other, non-hormonal methods of contraception should be used.

If you are a diabetic on insulin or tablets, your daily dose might need to be changed, your doctor will advise you.

What about food and drink?

Cyclo-Progynova 2 mg is not known to react with any types of food and drink.

What to do if you see a different doctor or have to go to hospital for treatment.

If you see any other doctor or go to hospital for treatment, tell your doctor about all your medicines, including Cyclo-Progynova 2 mg.

Special warnings

Lactose

This product contains lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

You should stop taking your tablets and tell your doctor if you:

develop any of the conditions listed in this leaflet under "You must not take Cyclo-Progynova". start developing headaches or migraines develop jaundice or problems with your liver become pregnant experience pain, tingling or numbness in any part of the body experience sudden chest pain

Cyclo-Progynova 2 mg must also be stopped at once if your doctor finds your blood pressure to be significantly raised.

Taking your medicine How to take your Cyclo-Progynova 2 mg

It is usually recommended that Cyclo-Progynova is taken at the lowest dose which is effective and for the shortest time possible.

About the pack:

The pack of Cyclo-Progynova 2 mg is designed to help you take your tablets. To use it you must first know the day of the week on which you will take the first tablet. If you are still having your periods, take the first tablet on the fifth day of your period, whether the period has finished or not. If your periods have become infrequent or have stopped altogether, your doctor may have advised you to start Cyclo-Progynova 2 mg immediately. If you have been taking a continuous HRT product (i.e. you take the same dose each day) you may change to Cyclo-Progynova 2 mg on any day. If you have been taking an HRT product which is followed by a withdrawal bleed, you should complete the cycle of treatment before changing to Cyclo-Progynova 2 mg.

In addition to the memo-pack (which contains the tablets), the outer carton contains a self adhesive blue sticker showing the days of the week. Peel the circular sticker off its backing and stick it in the centre of the memo-pack so that the day on which you start taking the tablets is directly underneath the red segment marked 'Start'.

For instance, if you are to start the tablets on a Wednesday, then stick a 'Wed' directly underneath the red segment marked 'Start'. You can now see on which day you have to take each tablet. Simply take one tablet each day, following the direction of the arrows on the foil, until the pack is empty. This means that you will be taking one white tablet for the first 11 days and then one pale brown tablet daily for the following 10 days. If, at any time, you are in doubt whether you have taken your tablet, a glance at the appropriate day on the memo-pack will tell you.

When you have finished taking your pack, you must leave a tablet free interval of seven days (unless your doctor decides otherwise). During this week, bleeding similar to a period may occur. This is normal.

Start your next pack of Cyclo-Progynova 2 mg immediately after this seven day break, whether the bleeding has stopped or not. You will in fact start on the same day of the week that you started your previous pack and the same will be true for each successive pack.

It is best to take your tablet at the same time each day, preferably after a meal. The tablet should not be chewed or sucked, but swallowed whole with a glass of water.

What to do if you forget to take a tablet

Take it as soon as possible, and take the next one at your normal time. If you are more than twelve hours late, leave the forgotten tablet in the pack. Continue to take the remaining tablets at the usual time on the right days.

You may experience some vaginal bleeding (breakthrough bleeding) if you have missed a tablet. This is normal.

What to do if you take too many tablets at once

There have been no reports of ill effects from taking too many tablets.

You should consult your doctor who will be able to advise you what action, if any, is necessary.

What bleeding to expect (what to do if your bleeding pattern seems different)

Just as with normal periods, the amount of bleeding with Cyclo-Progynova 2 mg varies from woman to woman. Usually the blood loss is not unduly heavy and it may even be rather scanty, but this is not important as far as the treatment is concerned. If you have recently had very light, short periods, you may have rather heavier blood loss with Cyclo-Progynova 2 mg.

If you are still menstruating, you will probably have regular blood loss 2 – 3 days after finishing each pack of Cyclo-Progynova 2 mg. If you miss a period, the possibility of pregnancy should be investigated.

Ask your doctor for advice.

If you have stopped having periods, Cyclo-Progynova 2 mg will probably cause you to experience blood loss again after the end of each pack, but may not always do so.

If blood loss occurs during the three weeks in which you are taking the tablets, let your doctor know. This may be a sign that your endometrium is getting thicker (see section on Endometrial Cancer in this leaflet). It is not necessary to stop taking your tablets unless your doctor tells you to.

After taking your medicine

During the first few months of treatment you may experience some vaginal bleeding at unexpected times (breakthrough bleeding and spotting) and some breast tenderness or enlargement. These symptoms are usually temporary and normally disappear with continued treatment. If they don't, contact your doctor.

All women have a small chance of having a blood clot in the veins of the leg, in the lung or other parts of the body whether or not they take HRT. If you think you have developed a blood clot while you are taking Cyclo-Progynova 2 mg you should stop taking it immediately and contact your doctor. The warning signs to look out for are listed in this leaflet in the section on Blood Clots under What you should know before taking Cyclo-Progynova.

The following symptoms have been reported: indigestion, nausea, vomiting, bloated stomach, increased appetite, increased or reduced weight, leg pains, fluid retention, palpitations, dizziness, anxiety, headaches, depressive moods, rashes, altered sexual interest. Tell your doctor if you have any of these symptoms, or, indeed, any other symptoms while you are taking Cyclo-Progynova 2 mg.

If you have any of the symptoms of heart disease, stroke or blood clots, breast, endometrial or ovarian cancer, as described earlier in this leaflet, tell your doctor.

Dementia: HRT will not prevent memory loss. In one study of women who started using combined HRT after the age of 65, a small increase in the risk of dementia was observed.

How to store your medicine

Keep your medicine in a safe place where children cannot see or reach it. Your medicine could harm them.

Do not use your medicines after the expiry date on the box, even if there is some medicine left after this date. Ask your doctor for a replacement prescription.

This leaflet was amended in November 2007

Cyclo-Progynova is a registered trademark of Schering AG.

© MEDA

United Kingdom 80620633_1107


read more


Elleste Duet Conti Tablets


Elleste DuetTM Conti Tablets

(estradiol and norethisterone acetate)

Read all of this leaflet carefully before you start using this medicine. Keep this leaflet. You may need to read it again. If you have any further questions, please ask your doctor or pharmacist. This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours. If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist. In this leaflet: 1. What Elleste Duet Conti Tablets are and what they are used for 2. Before you take Elleste Duet Conti Tablets 3. How to take Elleste Duet Conti Tablets 4. Possible side effects 5. How to store Elleste Duet Conti Tablets 6. Further information What Elleste Duet Conti Tablets Are And What They Are Used For

Elleste Duet Conti Tablets are a form of hormone replacement therapy (HRT).

They contain two hormones, estradiol hemihydrate and norethisterone acetate. Elleste Duet Conti Tablets are one of a group of medicines called combined estrogen-progestogen preparations. They are not an oral contraceptive.

Why has your doctor given you Elleste Duet Conti Tablets?

Elleste Duet Conti Tablets treat the symptoms of the menopause (change of life) in women who are at least one year past the menopause.

As you approach the menopause, your ovaries gradually produce fewer hormones. This may cause unpleasant symptoms such as hot flushes and sweating. Elleste Duet Conti Tablets replace hormones which you lose during the menopause and prevent or relieve any unpleasant symptoms. Your doctor will aim to give you the lowest dose required to treat your symptoms.

Other changes in your bones may also take place over a longer time. These changes can lead to an increased risk of your bones breaking or cracking. If you are at an increased risk of fractures due to osteoporosis (thinning of the bones) but are unable to take other treatments or if other therapies prove to be ineffective, Elleste Duet Conti Tablets may also be used for this purpose. Your doctor should discuss all the available options with you.

Before You Take Elleste Duet Conti Tablets

Elleste Duet Conti Tablets may not be suitable for all women. Read the list below.

DO NOT take Elleste Duet Conti Tablets, if you have, or have ever had:

a blood clot in a vein in your leg or anywhere else (a "deep vein thrombosis"); a blood clot that has travelled to your lung or another part of the body (an "embolus"); narrowed or blocked arteries possibly leading to angina and heart disease; breast or womb cancer; unexplained vaginal bleeding; liver problems, for example, jaundice (yellowing of the skin or eyes); porphyria (a rare inherited blood disease); untreated endometrial hyperplasia (an overgrowth of the lining of the womb).

Also do not take Elleste Duet Conti Tablets if you:

are pregnant or you think you could be pregnant; are breast-feeding; or have ever had an allergic reaction to any of the ingredients in Elleste Duet Conti Tablets (see Section 6).

Elleste Duet Conti Tablets contain lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

Safety of HRT

As well as benefits, HRT has some risks which you need to consider when you're deciding whether to take it, or whether to carry on taking it.

Take special care with Elleste Duet Conti Tablets

Elleste Duet Conti Tablets might have an effect on various processes in your body. HRT should only be started for symptoms that reduce your quality of life.

Medical check-ups

Before you start taking HRT, your doctor should ask about your own and your family's medical history. Your doctor may decide to examine your breasts and/or abdomen, and may do an internal examination - but only if these examinations are necessary for you, or if you have any special concerns.

Once you've started on HRT, you should:

see your doctor for regular check-ups (at least once a year). At these check-ups, your doctor may discuss with you the benefits and risks of continuing to take HRT; go for regular breast screening and cervical smear tests; regularly check your breasts for any changes such as dimpling of the skin, changes in the nipple, or any lumps you can see or feel. Effects on your heart or circulation

Heart disease:

HRT is not recommended for women who have heart disease, or have had heart disease recently.

If you have ever had heart disease, talk to your doctor to see if you should be taking HRT.

HRT will not help to prevent heart disease.

Studies with one type of HRT (containing conjugated estrogen plus the progestogen MPA) have shown that women may be slightly more likely to get heart disease during the first year of taking the medication. For other types of HRT, the risk is likely to be similar, although this is not yet certain.

If you get:

a pain in your chest that spreads to your arm or neck

See a doctor as soon as possible and do not take any more HRT until your doctor says you can. This pain could be a sign of heart disease.

Stroke:

Recent research suggests that HRT slightly increases the risk of having a stroke. Other things that can increase the risk of stroke include:

getting older high blood pressure smoking drinking too much alcohol an irregular heartbeat.

If you are worried about any of these things, or if you have had a stroke in the past, talk to your doctor to see if you should take HRT.

Compare

Looking at women in their 50s who are not taking HRT - on average, over a 5-year period, 3 in 1000 would be expected to have a stroke.

For women in their 50s who are taking HRT, the figure would be 4 in 1000.

Looking at women in their 60s who are not taking HRT - on average, over a 5-year period, 11 in 1000 would be expected to have a stroke.

For women in their 60s who are taking HRT, the figure would be 15 in 1000.

If you get:

unexplained migraine-type headaches, with or without disturbed vision

See a doctor as soon as possible and do not take any more HRT until your doctor says you can. These headaches may be an early warning sign of a stroke.

Blood clots:

HRT may increase the risk of blood clots in the veins (also called deep vein thrombosis, or DVT), especially during the first year of taking it.

These blood clots are not always serious, but if one travels to the lungs, it can cause chest pain, breathlessness, collapse or even death. This condition is called pulmonary embolism, or PE.

DVT and PE are examples of a condition called venous thromboembolism, or VTE.

You are more likely to get a blood clot if you:

are seriously overweight have had a blood clot before or have a close family member who has had blood clots have had one or more miscarriages have any blood clotting problem that needs treatment with a medicine such as warfarin are off your feet for a long time because of major surgery, injury or illness have a rare condition called systematic lupus erythematosus (SLE).

If any of these apply to you, talk to your doctor to see if you should take HRT.

Compare

Looking at women in their 50s who are not taking HRT - on average, over a 5-year period, 3 in 1000 would be expected to get a blood clot.

For women in their 50s who are taking HRT, the figure would be 7 in 1000.

Looking at women in their 60s who are not taking HRT - on average, over a 5-year period, 8 in 1000 would be expected to get a blood clot.

For women in their 60s who are taking HRT, the figure would be 17 in 1000.

The following may be signs of a blood clot if you get:

painful swellling in your leg sudden chest pain difficulty breathing

See a doctor as soon as possible and do not take any more HRT until your doctor says you can.

If you're going to have surgery, make sure your doctor knows about it. You may need to stop taking HRT about 4 to 6 weeks before the operation, to reduce the risk of a blood clot. Your doctor will tell you when you can start taking HRT again.

Effects on your risk of developing cancer

Breast cancer:

Women who have breast cancer, or have had breast cancer in the past, should not take HRT.

Taking HRT slightly increases the risk of breast cancer; as does having a later menopause. Your risk of breast cancer is higher if you:

have a close relative (mother, sister or grandmother) who has had breast cancer are seriously overweight.

The risk for a post-menopausal woman taking estrogen-only HRT for 5 years is about the same as for a woman of the same age who is still having periods over that time and not taking HRT. The risk for a woman who is taking estrogen plus progestogen HRT is higher than for estrogen-only HRT (but estrogen plus progestogen HRT is beneficial for the endometrium, see 'Endometrial cancer' below).

For all kinds of HRT, the extra risk of breast cancer increases the longer you take it, but returns to normal within about 5 years after stopping.

Compare

Looking at women in their 50s who are not taking HRT - on average, 32 in 1000 will be diagnosed with breast cancer by the time they reach the age of 65.

For women who start taking estrogen-only HRT at age 50 and take it for 5 years, the figure will be between 33 and 34 in 1000 (ie an extra 1-2 cases).

If they take estrogen-only HRT for 10 years, the figure will be 37 in 1000 (ie an extra 5 cases).

For women who start taking estrogen plus progestogen HRT at age 50 and take it for 5 years, the figure will be 38 in 1000 (ie an extra 6 cases).

If they take estrogen plus progestogen HRT for 10 years, the figure will be 51 in 1000 (ie an extra 19 cases).

If you notice any changes in your breasts such as:

dimpling of the skin changes in the nipple any lumps you can see or feel

Make an appointment to see your doctor as soon as possible.

Endometrial cancer (cancer of the lining of the womb):

Taking estrogen-only HRT for a long time can increase the risk of cancer of the lining of the womb (the endometrium). Taking progestogen as well as the estrogen helps to lower the extra risk.

Elleste Duet Conti Tablets also contain progestogen.

If you still have your womb, your doctor may prescribe a progestogen as well as estrogen. These may be prescribed separately, or as a combined HRT product.

If you have had your womb removed (a hysterectomy), your doctor will discuss with you whether you can safely take estrogen without a progestogen.

If you've had your womb removed because of endometriosis, any endometrium left in your body may be at risk. So your doctor may prescribe HRT that includes a progestogen as well as an estrogen.

Compare

Looking at women who still have a uterus and who are not taking HRT - on average 5 in 1000 will be diagnosed with endometrial cancer between the ages of 50-65.

For women who take estrogen-only HRT, the figure will be between 10 and 60 in 1000 (ie an extra 5 to 55 cases), depending on the dose and how long you take it.

The addition of a progestogen to estrogen-only HRT substantially reduces the risk of endometrial cancer.

If you get breakthrough bleeding or spotting, it's usually nothing to worry about, especially during the first few months of taking HRT.

Make an appointment to see your doctor if the bleeding or spotting:

carries on for more than the first few months starts after you've been on HRT for a while carries on even after you've stopped taking HRT

It could be that your endometrium has become thicker.

Ovarian cancer:

Ovarian cancer (cancer of the ovaries) is very rare, but it is serious. It can be difficult to diagnose, because there are often no obvious signs of the disease.

Some studies have indicated that taking estrogen-only HRT for more than 5 years may increase the risk of ovarian cancer. It is not yet known whether other kinds of HRT increase the risk in the same way.

While you are taking Elleste Duet Conti Tablets

Certain diseases sometimes get worse when you are taking hormone replacement therapy. Your doctor may need to check you more closely if you suffer from any of the following.

Migraine or severe headache Asthma Gallstones Epilepsy High blood pressure A personal or family history of blood clots. Diabetes (see below) Liver problems Heart or kidney problems Endometrial hyperplasia (overgrowth of the lining of your womb) Fibroids in your womb (see below) Endometriosis (where tissue from your womb is found outside the womb). A history of breast cancer in your family Systemic lupus erythematosus (SLE; a chronic inflammatory disease affecting the skin and organs) Otosclerosis (an inherited form of deafness which sometimes gets worse during pregnancy). High levels of lipids in you blood (hypertriglyceridaemia)

Elleste Duet Conti Tablets may affect the results of certain laboratory tests, so tell the person taking the sample that you are taking Elleste Duet Conti Tablets.

If you have:

fibroids (lumps of fibrous and muscular tissue) in your womb, these may increase in size when you are taking Elleste Duet Conti Tablets. See your doctor if you have any pain or swelling in your abdomen. diabetes, you may need to change the amount of insulin you take. Check your blood glucose level more often until it is steady.

Do I need to use contraception while I am taking Elleste Duet Conti Tablets?

It is important to remember that Elleste Duet Conti Tablets are not an oral contraceptive (the pill).

If you are using the pill or another hormonal contraceptive, you will need to use another type of contraceptive. Please discuss this with your doctor.

Taking other medicines with Elleste Duet Conti Tablets

Please tell your doctor or pharmacist if you are using or have recently used any other medicines, including over-the-counter medicines.

In particular, tell your doctor if you are using any of the following because they may alter the effects of Elleste Duet Conti Tablets:

drugs that treat epilepsy, some anti-infectives (anti-virals or antibiotics) and sedatives. herbal medicines containing St. John's Wort: diabetic drugs, as this product may affect your blood glucose level. If you are being treated for diabetes please let your doctor or pharmacist know that you take Elleste Duet Conti.

If your doctor does not know that you are taking these other medicines, tell him or her before you start taking Elleste Duet Conti Tablets.

Pregnancy and breast-feeding

Elleste Duet Conti Tablets are for use in post-menopausal women. They should not be taken by pregnant or breast-feeding women.

Driving or using machines

No effects on driving or using machinery have been observed for Elleste Duet Conti Tablets.

Important information about some of the ingredients of Elleste Duet Conti Tablets

Elleste Duet Conti Tablets contain lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

How To Take Elleste Duet Conti Tablets If you are not taking any HRT

If you are not taking any HRT, you can start taking Elleste Duet Conti Tablets straightaway.

Take one tablet each day. You can take the tablets at a time of the day that suits you, but it is best to take them at about the same time each day. Swallow the tablets whole, with some water. All the tablets are the same. The days are marked on the strip to help you to remember to take one each day. Follow the direction of the arrows on the pack and take a tablet every day until the pack is empty. When you finish a foil strip, start a new strip the next day. Changing from another type of HRT

If you are changing from another type of HRT, and you usually have a monthly bleed, start taking Elleste Duet Conti Tablets on the first day of bleeding.

If you do not have a monthly bleed, start taking Elleste Duet Conti Tablets on any convenient day.

If your doctor gives you instructions on changing from another type of HRT you should follow these instructions. If you have any doubts you should contact your doctor.

Will I have periods?

You should not have monthly periods. In the first few months you may get some breakthrough bleeding or spotting. As you continue to take Elleste Duet Conti Tablets, some women will continue to have light spotting and some women will not bleed at all.

Tell your doctor if you:

still getting some bleeding after the first 3 to 4 months and this is a problem for you; don't bleed for a long time, but then start bleeding again. If you forget to take a tablet

Take the tablet as soon as you remember, and take the next one at the normal time.

If you have missed your tablet by more than 12 hours, dispose of this tablet safely and take the next one at the normal time. You may experience some breakthrough bleeding or spotting.

If you take more than you should

There should be no problems, but you may feel sick or actually be sick. If you are worried, contact your doctor. Take the usual tablet the following day.

Possible Side Effects

Like all medicines, Elleste Duet Conti Tablets can cause side effects, although not everybody gets them. If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

Stop taking the tablets immediately and tell your doctor if: you become jaundiced (your skin or the whites of your eyes look yellow); you have itching all over your body; you have an unusual, severe or prolonged headache; your sight is affected in any way; you find it difficult to speak; any part of your body suddenly feels weak or numb; there is a chance that you could be or could become pregnant; or you develop any of the conditions listed under "Before you take Elleste Duet Conti Tablets".

During the first few months you may feel sick, have headaches, or your breasts may be painful or increase in size. These side effects should lessen as your body gets used to the medicine.

You may also get the following side effects:

Common: feeling sick, stomach cramps, headache, an increase in size of fibroids in the womb, breakthrough bleeding, changes in weight, oedema (swelling) of legs, breast tenderness and enlargement, mood changes, changes in sex drive.

Uncommon: indigestion, being sick, flatulence, gallstones and gallbladder disease, feeling dizzy, migraine, vaginal thrush, increase in blood pressure, leg cramps, breast cancer (please refer to the earlier section on breast cancer).

Rare: loss of hair from the scalp, increase in body and facial hair, itchiness, rashes, thromboembolic disease (please refer to the earlier section on the effects of HRT on the heart and circulation).

Very rare: heart disease (please refer to the earlier section on the effects of HRT on the heart and circulation), stroke, chloasma (brown patches on the skin), red swellings on the skin.

HRT will not prevent memory loss. In one study of women who started using combined HRT after the age of 65, a small increase in the risk of dementia was observed.

How To Store Elleste Duet Conti Tablets

Keep out of the reach and sight of children.

Do not store above 25°C. Store in the original package.

Do not take Elleste Duet Conti Tablets after the 'expiry date' shown on the box.

If your tablets are out of date, take them to your pharmacist who will dispose of them safely.

Further Information What Elleste Duet Conti Tablets contains Each tablet contains the active ingredients: 2 milligrams estradiol (as hemihydrate) and 1 milligram norethisterone acetate.
(The estradiol used to make Elleste Duet Conti Tablets does not come from animals). The tablets also contain: lactose monohydrate, maize starch, povidone, talc, magnesium stearate, macrogol 400, titanium dioxide (E171), black iron oxide (E172), and hypromellose (E464) (see also the warning at the end of section 2). What Elleste Duet Conti Tablets look like and contents of the pack

Elleste Duet Conti Tablets are grey film-coated tablets with an embossing.

They are supplied in three blister strips in each pack. Each strip contains 28 tablets.

Marketing Authorisation Holder Meda Pharmaceuticals Ltd Skyway House Parsonage Road Takeley Bishop's Stortford CM22 6PU UK Manufacturer Piramal Healthcare UK Ltd. Whalton Road Morpeth Northumberland NE61 3YA UK

This leaflet was last approved in October 2009.

If you have any comments on the way this leaflet is written, please write to

Meda Pharmaceuticals Ltd Skyway House Parsonage Road Takeley Bishop's Stortford CM22 6PU UK

20701188

5029/PIL8


read more


Lasix


Generic Name: furosemide
Dosage Form: tablet
Lasix®
(furosemide)
Tablets 20, 40, and 80 mg Warning

Lasix® (furosemide) is a potent diuretic which, if given in excessive amounts, can lead to a profound diuresis with water and electrolyte depletion. Therefore, careful medical supervision is required and dose and dose schedule must be adjusted to the individual patient's needs. (See DOSAGE AND ADMINISTRATION.)

Lasix Description

Lasix® is a diuretic which is an anthranilic acid derivative. Lasix tablets for oral administration contain furosemide as the active ingredient and the following inactive ingredients: lactose monohydrate NF, magnesium stearate NF, starch NF, talc USP, and colloidal silicon dioxide NF. Chemically, it is 4-chloro-N-furfuryl-5-sulfamoylanthranilic acid. Lasix is available as white tablets for oral administration in dosage strengths of 20, 40 and 80 mg. Furosemide is a white to off-white odorless crystalline powder. It is practically insoluble in water, sparingly soluble in alcohol, freely soluble in dilute alkali solutions and insoluble in dilute acids.

The CAS Registry Number is 54-31-9.

The structural formula is as follows:

Lasix - Clinical Pharmacology

Investigations into the mode of action of Lasix have utilized micropuncture studies in rats, stop flow experiments in dogs and various clearance studies in both humans and experimental animals. It has been demonstrated that Lasix inhibits primarily the absorption of sodium and chloride not only in the proximal and distal tubules but also in the loop of Henle. The high degree of efficacy is largely due to the unique site of action. The action on the distal tubule is independent of any inhibitory effect on carbonic anhydrase and aldosterone.

Recent evidence suggests that furosemide glucuronide is the only or at least the major biotransformation product of furosemide in man. Furosemide is extensively bound to plasma proteins, mainly to albumin. Plasma concentrations ranging from 1 to 400 ?g/mL are 91 to 99% bound in healthy individuals. The unbound fraction averages 2.3 to 4.1% at therapeutic concentrations.

The onset of diuresis following oral administration is within 1 hour. The peak effect occurs within the first or second hour. The duration of diuretic effect is 6 to 8 hours.

In fasted normal men, the mean bioavailability of furosemide from Lasix Tablets and Lasix Oral Solution is 64% and 60%, respectively, of that from an intravenous injection of the drug. Although furosemide is more rapidly absorbed from the oral solution (50 minutes) than from the tablet (87 minutes), peak plasma levels and area under the plasma concentration-time curves do not differ significantly. Peak plasma concentrations increase with increasing dose but times-to-peak do not differ among doses. The terminal half-life of furosemide is approximately 2 hours.

Significantly more furosemide is excreted in urine following the IV injection than after the tablet or oral solution. There are no significant differences between the two oral formulations in the amount of unchanged drug excreted in urine.

Geriatric Population

Furosemide binding to albumin may be reduced in elderly patients. Furosemide is predominantly excreted unchanged in the urine. The renal clearance of furosemide after intravenous administration in older healthy male subjects (60–70 years of age) is statistically significantly smaller than in younger healthy male subjects (20–35 years of age). The initial diuretic effect of furosemide in older subjects is decreased relative to younger subjects. (See PRECAUTIONS: Geriatric Use.)

Indications and Usage for Lasix Edema

Lasix is indicated in adults and pediatric patients for the treatment of edema associated with congestive heart failure, cirrhosis of the liver, and renal disease, including the nephrotic syndrome. Lasix is particularly useful when an agent with greater diuretic potential is desired.

Hypertension

Oral Lasix may be used in adults for the treatment of hypertension alone or in combination with other antihypertensive agents. Hypertensive patients who cannot be adequately controlled with thiazides will probably also not be adequately controlled with Lasix alone.

Contraindications

Lasix is contraindicated in patients with anuria and in patients with a history of hypersensitivity to furosemide.

Warnings

In patients with hepatic cirrhosis and ascites, Lasix therapy is best initiated in the hospital. In hepatic coma and in states of electrolyte depletion, therapy should not be instituted until the basic condition is improved. Sudden alterations of fluid and electrolyte balance in patients with cirrhosis may precipitate hepatic coma; therefore, strict observation is necessary during the period of diuresis. Supplemental potassium chloride and, if required, an aldosterone antagonist are helpful in preventing hypokalemia and metabolic alkalosis.

If increasing azotemia and oliguria occur during treatment of severe progressive renal disease, Lasix should be discontinued.

Cases of tinnitus and reversible or irreversible hearing impairment and deafness have been reported. Reports usually indicate that Lasix ototoxicity is associated with rapid injection, severe renal impairment, the use of higher than recommended doses, hypoproteinemia or concomitant therapy with aminoglycoside antibiotics, ethacrynic acid, or other ototoxic drugs. If the physician elects to use high dose parenteral therapy, controlled intravenous infusion is advisable (for adults, an infusion rate not exceeding 4 mg Lasix per minute has been used). (See PRECAUTIONS: Drug Interactions)

Precautions General

Excessive diuresis may cause dehydration and blood volume reduction with circulatory collapse and possibly vascular thrombosis and embolism, particularly in elderly patients. As with any effective diuretic, electrolyte depletion may occur during Lasix therapy, especially in patients receiving higher doses and a restricted salt intake. Hypokalemia may develop with Lasix, especially with brisk diuresis, inadequate oral electrolyte intake, when cirrhosis is present, or during concomitant use of corticosteroids, ACTH, licorice in large amounts, or prolonged use of laxatives. Digitalis therapy may exaggerate metabolic effects of hypokalemia, especially myocardial effects.

All patients receiving Lasix therapy should be observed for these signs or symptoms of fluid or electrolyte imbalance (hyponatremia, hypochloremic alkalosis, hypokalemia, hypomagnesemia or hypocalcemia): dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, arrhythmia, or gastrointestinal disturbances such as nausea and vomiting. Increases in blood glucose and alterations in glucose tolerance tests (with abnormalities of the fasting and 2-hour postprandial sugar) have been observed, and rarely, precipitation of diabetes mellitus has been reported.

In patients with severe symptoms of urinary retention (because of bladder emptying disorders, prostatic hyperplasia, urethral narrowing), the administration of furosemide can cause acute urinary retention related to increased production and retention of urine. Thus, these patients require careful monitoring, especially during the initial stages of treatment.

In patients at high risk for radiocontrast nephropathy Lasix can lead to a higher incidence of deterioration in renal function after receiving radiocontrast compared to high-risk patients who received only intravenous hydration prior to receiving radiocontrast.

In patients with hypoproteinemia (e.g., associated with nephrotic syndrome) the effect of Lasix may be weakened and its ototoxicity potentiated.

Asymptomatic hyperuricemia can occur and gout may rarely be precipitated.

Patients allergic to sulfonamides may also be allergic to Lasix. The possibility exists of exacerbation or activation of systemic lupus erythematosus.

As with many other drugs, patients should be observed regularly for the possible occurrence of blood dyscrasias, liver or kidney damage, or other idiosyncratic reactions.

Information for Patients

Patients receiving Lasix should be advised that they may experience symptoms from excessive fluid and/or electrolyte losses. The postural hypotension that sometimes occurs can usually be managed by getting up slowly. Potassium supplements and/or dietary measures may be needed to control or avoid hypokalemia.

Patients with diabetes mellitus should be told that furosemide may increase blood glucose levels and thereby affect urine glucose tests. The skin of some patients may be more sensitive to the effects of sunlight while taking furosemide.

Hypertensive patients should avoid medications that may increase blood pressure, including over-the-counter products for appetite suppression and cold symptoms.

Laboratory Tests

Serum electrolytes (particularly potassium), CO2, creatinine and BUN should be determined frequently during the first few months of Lasix therapy and periodically thereafter. Serum and urine electrolyte determinations are particularly important when the patient is vomiting profusely or receiving parenteral fluids. Abnormalities should be corrected or the drug temporarily withdrawn. Other medications may also influence serum electrolytes.

Reversible elevations of BUN may occur and are associated with dehydration, which should be avoided, particularly in patients with renal insufficiency.

Urine and blood glucose should be checked periodically in diabetics receiving Lasix, even in those suspected of latent diabetes.

Lasix may lower serum levels of calcium (rarely cases of tetany have been reported) and magnesium. Accordingly, serum levels of these electrolytes should be determined periodically.

In premature infants Lasix may precipitate nephrocalcinosis/nephrolithiasis, therefore renal function must be monitored and renal ultrasonography performed. (See PRECAUTIONS: Pediatric Use)

Drug Interactions

Lasix may increase the ototoxic potential of aminoglycoside antibiotics, especially in the presence of impaired renal function. Except in life-threatening situations, avoid this combination.

Lasix should not be used concomitantly with ethacrynic acid because of the possibility of ototoxicity. Patients receiving high doses of salicylates concomitantly with Lasix, as in rheumatic disease, may experience salicylate toxicity at lower doses because of competitive renal excretory sites.

There is a risk of ototoxic effects if cisplatin and Lasix are given concomitantly. In addition, nephrotoxicity of nephrotoxic drugs such as cisplatin may be enhanced if Lasix is not given in lower doses and with positive fluid balance when used to achieve forced diuresis during cisplatin treatment.

Lasix has a tendency to antagonize the skeletal muscle relaxing effect of tubocurarine and may potentiate the action of succinylcholine.

Lithium generally should not be given with diuretics because they reduce lithium's renal clearance and add a high risk of lithium toxicity.

Lasix combined with angiotensin converting enzyme inhibitors or angiotensin II receptor blockers may lead to severe hypotension and deterioration in renal function, including renal failure. An interruption or reduction in the dosage of Lasix, angiotensin converting enzyme inhibitors, or angiotensin receptor blockers may be necessary.

Potentiation occurs with ganglionic or peripheral adrenergic blocking drugs.

Lasix may decrease arterial responsiveness to norepinephrine. However, norepinephrine may still be used effectively.

Simultaneous administration of sucralfate and Lasix tablets may reduce the natriuretic and antihypertensive effects of Lasix. Patients receiving both drugs should be observed closely to determine if the desired diuretic and/or antihypertensive effect of Lasix is achieved. The intake of Lasix and sucralfate should be separated by at least two hours.

In isolated cases, intravenous administration of Lasix within 24 hours of taking chloral hydrate may lead to flushing, sweating attacks, restlessness, nausea, increase in blood pressure and tachycardia. Use of Lasix concomitantly with chloral hydrate is, therefore, not recommended.

Phenytoin interferes directly with renal action of Lasix. There is evidence that treatment with phenytoin leads to decrease intestinal absorption of Lasix, and consequently to lower peak serum furosemide concentrations.

Methotrexate and other drugs that, like Lasix, undergo significant renal tubular secretion may reduce the effect of Lasix. Conversely, Lasix may decrease renal elimination of other drugs that undergo tubular secretion. High-dose treatment of both Lasix and these other drugs may result in elevated serum levels of these drugs and may potentiate their toxicity as well as the toxicity of Lasix.

Lasix can increase the risk of cephalosporin-induced nephrotoxicity even in the setting of minor or transient renal impairment.

Concomitant use of cyclosporine and Lasix is associated with increased risk of gouty arthritis secondary to Lasix-induced hyperurecemia and cyclosporine impairment of renal urate excretion.

One study in six subjects demonstrated that the combination of furosemide and acetylsalicylic acid temporarily reduced creatinine clearance in patients with chronic renal insufficiency. There are case reports of patients who developed increased BUN, serum creatinine and serum potassium levels, and weight gain when furosemide was used in conjunction with NSAIDs.

Literature reports indicate that coadministration of indomethacin may reduce the natriuretic and antihypertensive effects of Lasix (furosemide) in some patients by inhibiting prostaglandin synthesis. Indomethacin may also affect plasma renin levels, aldosterone excretion, and renin profile evaluation. Patients receiving both indomethacin and Lasix should be observed closely to determine if the desired diuretic and/or antihypertensive effect of Lasix is achieved.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Furosemide was tested for carcinogenicity by oral administration in one strain of mice and one strain of rats. A small but significantly increased incidence of mammary gland carcinomas occurred in female mice at a dose 17.5 times the maximum human dose of 600 mg. There were marginal increases in uncommon tumors in male rats at a dose of 15 mg/kg (slightly greater than the maximum human dose) but not at 30 mg/kg.

Furosemide was devoid of mutagenic activity in various strains of Salmonella typhimurium when tested in the presence or absence of an in vitro metabolic activation system, and questionably positive for gene mutation in mouse lymphoma cells in the presence of rat liver S9 at the highest dose tested. Furosemide did not induce sister chromatid exchange in human cells in vitro, but other studies on chromosomal aberrations in human cells in vitro gave conflicting results. In Chinese hamster cells it induced chromosomal damage but was questionably positive for sister chromatid exchange. Studies on the induction by furosemide of chromosomal aberrations in mice were inconclusive. The urine of rats treated with this drug did not induce gene conversion in Saccharomyces cerevisiae.

Lasix (furosemide) produced no impairment of fertility in male or female rats, at 100 mg/kg/day (the maximum effective diuretic dose in the rat and 8 times the maximal human dose of 600 mg/day).

Pregnancy

PREGNANCY CATEGORY C - Furosemide has been shown to cause unexplained maternal deaths and abortions in rabbits at 2, 4 and 8 times the maximal recommended human dose. There are no adequate and well-controlled studies in pregnant women. Lasix should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Treatment during pregnancy requires monitoring of fetal growth because of the potential for higher birth weights.

The effects of furosemide on embryonic and fetal development and on pregnant dams were studied in mice, rats and rabbits.

Furosemide caused unexplained maternal deaths and abortions in the rabbit at the lowest dose of 25 mg/kg (2 times the maximal recommended human dose of 600 mg/day). In another study, a dose of 50 mg/kg (4 times the maximal recommended human dose of 600 mg/day) also caused maternal deaths and abortions when administered to rabbits between Days 12 and 17 of gestation. In a third study, none of the pregnant rabbits survived a dose of 100 mg/kg. Data from the above studies indicate fetal lethality that can precede maternal deaths.

The results of the mouse study and one of the three rabbit studies also showed an increased incidence and severity of hydronephrosis (distention of the renal pelvis and, in some cases, of the ureters) in fetuses derived from the treated dams as compared with the incidence in fetuses from the control group.

Nursing Mothers

Because it appears in breast milk, caution should be exercised when Lasix is administered to a nursing mother.

Lasix may inhibit lactation.

Pediatric Use

In premature infants Lasix may precipitate nephrocalcinosis/nephrolithiasis.

Nephrocalcinosis/nephrolithiasis has also been observed in children under 4 years of age with no history of prematurity who have been treated chronically with Lasix. Monitor renal function, and renal ultrasonography should be considered, in pediatric patients receiving Lasix.

If Lasix is administered to premature infants during the first weeks of life, it may increase the risk of persistence of patent ductus arteriosus

Geriatric Use

Controlled clinical studies of Lasix did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for the elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection and it may be useful to monitor renal function. (See PRECAUTIONS: General and DOSAGE AND ADMINISTRATION.)

Adverse Reactions

Adverse reactions are categorized below by organ system and listed by decreasing severity.

Gastrointestinal System Reactions

hepatic encephalopathy in patients with hepatocellular insufficiency pancreatitis jaundice (intrahepatic cholestatic jaundice) increased liver enzymes anorexia oral and gastric irritation cramping diarrhea constipation nausea vomiting

Systemic Hypersensitivity Reactions

Severe anaphylactic or anaphylactoid reactions (e.g. with shock) systemic vasculitis interstitial nephritis necrotizing angiitis

Central Nervous System Reactions

tinnitus and hearing loss paresthesias vertigo dizziness headache blurred vision xanthopsia

Hematologic Reactions

aplastic anemia thrombocytopenia agranulocytosis hemolytic anemia leukopenia anemia eosinophilia

Dermatologic-Hypersensitivity Reactions

toxic epidermal necrolysis Stevens-Johnson Syndrome erythema multiforme drug rash with eosinophilia and systemic symptoms acute generalized exanthematous pustulosis exfoliative dermatitis bullous pemphigoid purpura photosensitivity rash pruritis urticaria

Cardiovascular Reaction

Orthostatic hypotension may occur and be aggravated by alcohol, barbiturates or narcotics. Increase in cholesterol and triglyceride serum levels

Other Reactions

hyperglycemia glycosuria hyperuricemia muscle spasm weakness restlessness urinary bladder spasm thrombophlebitis fever

Whenever adverse reactions are moderate or severe, Lasix dosage should be reduced or therapy withdrawn.

Overdosage

The principal signs and symptoms of overdose with Lasix are dehydration, blood volume reduction, hypotension, electrolyte imbalance, hypokalemia and hypochloremic alkalosis, and are extensions of its diuretic action.

The acute toxicity of Lasix has been determined in mice, rats and dogs. In all three, the oral LD50 exceeded 1000 mg/kg body weight, while the intravenous LD50 ranged from 300 to 680 mg/kg. The acute intragastric toxicity in neonatal rats is 7 to 10 times that of adult rats.

The concentration of Lasix in biological fluids associated with toxicity or death is not known.

Treatment of overdosage is supportive and consists of replacement of excessive fluid and electrolyte losses. Serum electrolytes, carbon dioxide level and blood pressure should be determined frequently. Adequate drainage must be assured in patients with urinary bladder outlet obstruction (such as prostatic hypertrophy).

Hemodialysis does not accelerate furosemide elimination.

Lasix Dosage and Administration Edema

Therapy should be individualized according to patient response to gain maximal therapeutic response and to determine the minimal dose needed to maintain that response.

Adults

The usual initial dose of Lasix is 20 to 80 mg given as a single dose. Ordinarily a prompt diuresis ensues. If needed, the same dose can be administered 6 to 8 hours later or the dose may be increased. The dose may be raised by 20 or 40 mg and given not sooner than 6 to 8 hours after the previous dose until the desired diuretic effect has been obtained. The individually determined single dose should then be given once or twice daily (eg, at 8 am and 2 pm). The dose of Lasix may be carefully titrated up to 600 mg/day in patients with clinically severe edematous states.

Edema may be most efficiently and safely mobilized by giving Lasix on 2 to 4 consecutive days each week.

When doses exceeding 80 mg/day are given for prolonged periods, careful clinical observation and laboratory monitoring are particularly advisable. (See PRECAUTIONS: Laboratory Tests.)

Geriatric patients

In general, dose selection for the elderly patient should be cautious, usually starting at the low end of the dosing range (see PRECAUTIONS: Geriatric Use).

Pediatric patients

The usual initial dose of oral Lasix in pediatric patients is 2 mg/kg body weight, given as a single dose. If the diuretic response is not satisfactory after the initial dose, dosage may be increased by 1 or 2 mg/kg no sooner than 6 to 8 hours after the previous dose. Doses greater than 6 mg/kg body weight are not recommended. For maintenance therapy in pediatric patients, the dose should be adjusted to the minimum effective level.

Hypertension

Therapy should be individualized according to the patient's response to gain maximal therapeutic response and to determine the minimal dose needed to maintain the therapeutic response.

Adults

The usual initial dose of Lasix for hypertension is 80 mg, usually divided into 40 mg twice a day. Dosage should then be adjusted according to response. If response is not satisfactory, add other antihypertensive agents.

Changes in blood pressure must be carefully monitored when Lasix is used with other antihypertensive drugs, especially during initial therapy. To prevent excessive drop in blood pressure, the dosage of other agents should be reduced by at least 50 percent when Lasix is added to the regimen. As the blood pressure falls under the potentiating effect of Lasix, a further reduction in dosage or even discontinuation of other antihypertensive drugs may be necessary.

Geriatric patients

In general, dose selection and dose adjustment for the elderly patient should be cautious, usually starting at the low end of the dosing range (see PRECAUTIONS: Geriatric Use).

How is Lasix Supplied

Lasix (furosemide) Tablets 20 mg are supplied as white, oval, monogrammed tablets in Bottles of 100 (NDC 0039-0067-10), and 1000 (NDC 0039-0067-70). The 20 mg tablets are imprinted with "Lasix®" on one side.

Lasix Tablets 40 mg are supplied as white, round, monogrammed, scored tablets in Bottles of 100 (NDC 0039-0060-13), 500 (NDC 0039-0060-50), and 1000 (NDC 0039-0060-70). The 40 mg tablets are imprinted with "Lasix® 40" on one side.

Lasix Tablets 80 mg are supplied as white, round, monogrammed, facetted edge tablets in Bottles of 50 (NDC 0039-0066-05) and 500 (NDC 0039-0066-50). The 80 mg tablets are imprinted with "Lasix® 80" on one side.

Note: Dispense in well-closed, light-resistant containers. Exposure to light might cause a slight discoloration. Discolored tablets should not be dispensed.

Tested by USP Dissolution Test 2

Store at 25° C (77° F); excursions permitted to 15 – 30° C (59 – 86° F). [See USP Controlled Room Temperature.]

Revised August 2011

sanofi-aventis U.S. LLC
Bridgewater, NJ 08807

© 2011 sanofi-aventis U.S. LLC

PRINCIPAL DISPLAY PANEL - 20 mg Bottle Label

NDC 0039-0067-10

Lasix®

furosemide

Tablets

100 Tablets

20mg

sanofi aventis

PRINCIPAL DISPLAY PANEL - 40 mg Bottle Label

NDC 0039-0060-13

Lasix®

furosemide

Tablets

100 Tablets

40mg

sanofi aventis

PRINCIPAL DISPLAY PANEL - 80 mg Bottle Label

NDC 0039-0066-05

Lasix®

furosemide

Tablets

50 Tablets

80mg

sanofi aventis


Lasix 
furosemide  tablet Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0039-0067 Route of Administration ORAL DEA Schedule      Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength furosemide (furosemide) furosemide 20 mg Inactive Ingredients Ingredient Name Strength lactose monohydrate   magnesium stearate   talc   silicon dioxide   Product Characteristics Color WHITE Score no score Shape OVAL (ellipsoidal) Size 8mm Flavor Imprint Code Lasix Contains          Packaging # NDC Package Description Multilevel Packaging 1 0039-0067-10 100 TABLET In 1 BOTTLE None 2 0039-0067-70 1000 TABLET In 1 BOTTLE None
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA016273 07/01/1966
Lasix 
furosemide  tablet Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0039-0060 Route of Administration ORAL DEA Schedule      Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength furosemide (furosemide) furosemide 40 mg Inactive Ingredients Ingredient Name Strength lactose monohydrate   magnesium stearate   talc   silicon dioxide   Product Characteristics Color WHITE Score 2 pieces Shape ROUND Size 8mm Flavor Imprint Code Lasix;40 Contains          Packaging # NDC Package Description Multilevel Packaging 1 0039-0060-13 100 TABLET In 1 BOTTLE None 2 0039-0060-50 500 TABLET In 1 BOTTLE None 3 0039-0060-70 1000 TABLET In 1 BOTTLE None
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA016273 07/01/1966
Lasix 
furosemide  tablet Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0039-0066 Route of Administration ORAL DEA Schedule      Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength furosemide (furosemide) furosemide 80 mg Inactive Ingredients Ingredient Name Strength lactose monohydrate   magnesium stearate   talc   silicon dioxide   Product Characteristics Color WHITE Score 2 pieces Shape ROUND Size 10mm Flavor Imprint Code Lasix;80 Contains          Packaging # NDC Package Description Multilevel Packaging 1 0039-0066-05 50 TABLET In 1 BOTTLE None 2 0039-0066-50 500 TABLET In 1 BOTTLE None
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA016273 07/01/1966
Labeler - Sanofi-Aventis U.S. LLC (824676584) Establishment Name Address ID/FEI Operations Sanofi-Aventis Canada Inc. 251046934 MANUFACTURE Revised: 09/2011Sanofi-Aventis U.S. LLC More Lasix resources Lasix Side Effects (in more detail) Lasix Dosage Lasix Use in Pregnancy & Breastfeeding Drug Images Lasix Drug Interactions Lasix Support Group 12 Reviews for Lasix - Add your own review/rating Lasix Monograph (AHFS DI) Lasix Advanced Consumer (Micromedex) - Includes Dosage Information Lasix MedFacts Consumer Leaflet (Wolters Kluwer) Lasix Consumer Overview Furosemide Professional Patient Advice (Wolters Kluwer) Furosemide MedFacts Consumer Leaflet (Wolters Kluwer) Compare Lasix with other medications Ascites Edema Heart Failure High Blood Pressure Hypercalcemia Nonobstructive Oliguria Oliguria Pulmonary Edema Renal Failure Renal Transplant
read more


Kliofem


Kliofem

2 mg/1 mg film-coated tablets

Estradiol hemihydrate and norethisterone acetate

Read all of this leaflet carefully before you start taking this medicine. Keep this leaflet. You may need to read it again If you have further questions, ask your doctor or pharmacist This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist. In this leaflet:

1. What Kliofem is and what it is used for
2. Before you take Kliofem
3. How to use Kliofem
4. Possible side effects
5. How to store Kliofem
6. Further information

What Kliofem is and what it is used for

Kliofem belongs to a group of hormone replacement therapy (HRT) medicines, called continuous combined HRT which are taken every day without interruptions.

Kliofem contains the female sex hormone estradiol and norethisterone acetate. The estradiol in Kliofem is identical to the estradiol in the ovaries of women, and is classified as a natural oestrogen. Norethisterone acetate is a synthetic progestagen, which acts in a similar manner as the body’s own hormone progesterone, another important female sex hormone.

Kliofem is prescribed:

To relieve unpleasant symptoms like hot flushes, night sweats and vaginal dryness, which occur when the oestrogen levels decline and the periods stop (menopause). For the prevention of osteoporosis (thinning of the bones) in postmenopausal women if they are at high risk of future fractures and if they are unable to take other medications for this purpose.

Kliofem is prescribed for women who have not had their womb removed, and whose periods stopped more than a year ago.

There is only limited experience of treating women older than 65 years with Kliofem.

Before you take Kliofem Medical check-ups

Before you start taking HRT your doctor should ask about your own and your family’s medical history. Your doctor may decide to examine your breasts and/or your abdomen, and may do an internal examination - but only if these examinations are necessary for you, or if you have any special concerns.

Once you’ve started on HRT, you should see your doctor for regular check-ups (at least once a year). At these check-ups, your doctor may discuss with you the benefits and risks of continuing to take HRT.

For more information about the safety of HRT, see section 4 “Possible side effects”

Be sure to:

Go for regular breast screening and cervical smear tests Regularly check your breasts for any changes such as dimpling of the skin, changes in the nipple, or any lumps you can see or feel. Do not take Kliofem

If any of the following applies to you, talk to your doctor. Do not start taking Kliofem:

If you have or have had breast cancer, or if it is suspected If you have cancer of the womb lining (endometrium), or if such an oestrogen dependent cancer is suspected If you have any vaginal bleeding, which has not been diagnosed by your doctor If you have or have had endometrial hyperplasia (excessive growth of the womb lining) that is not being treated If you have or previously have had a blood clot in the blood vessels of the legs or the lungs (like deep vein thrombosis or lung embolism) If you have recently had a heart attack, stroke, or have angina If you have or have had a liver disorder and your liver tests have not returned to normal If you have porphyria (a liver enzyme disease) If you are allergic (hypersensitive) to estradiol, norethisterone acetate or any other ingredients in Kliofem (listed in section 6,“Further information”). Take special care with Kliofem

If you have (or have had) any of the following conditions, tell your doctor. Your doctor may then want to follow your treatment up more closely. Rarely, these conditions may come back or get worse during treatment with Kliofem:

If you have any condition affecting the womb lining, such as fibroids, endometriosis (presence of womb lining tissue outside the womb) or have had endometrial hyperplasia (excessive growth of the womb lining) If you have a history of blood clots (thrombosis) or have risk factors for blood clots (these risk factors and symptoms for a blood clot are listed in section 4,“Possible side effects”) If any of your immediate family has had breast cancer, or other cancers related to oestrogen (e.g. endometrial cancer) If you have high blood pressure If you have a liver disorder such as liver adenoma (a benign tumour) If you have a kidney or heart disorder If you have diabetes If you have gallstone disease If you have epilepsy If you have asthma If you get migraines or severe headaches If you have systemic lupus erythematosus (SLE) If you have high levels of fat in the blood (hypertriglyceridemia) If you have otosclerosis (hearing loss sometimes linked to pregnancy).

If you need a blood test, tell your doctor that you are taking Kliofem, since oestrogen can affect the results of certain laboratory tests.

If you are going to have surgery, talk to your doctor. You may need to stop taking these tablets 4 to 6 weeks before the operation, to reduce the risk of a blood clot. Your doctor will tell you when you can start treatment again

Stop taking Kliofem

If you experience any of the following conditions below, stop taking Kliofem, and contact your doctor immediately:

If you get a migraine-type headache for the first time If you develop yellow skin or eyes (jaundice) or other liver problems If your blood pressure goes up while you’re taking Kliofem If you become pregnant If any of the conditions listed in Section 2“Before you take Kliofem”, occur. Using other medicines

Some medicines may reduce the effects of Kliofem:

Drugs used for epilepsy (such as phenobarbital, phenytoin and carbamazepin) Drugs used for tuberculosis (such as rifampicin, rifabutin) Drugs used for HIV infections (such as nevirapine, efavirenz, ritonavir and nelfinavir) Herbal products with St John’s Wort (Hypericum perforatum).

Other medicines may increase the effects of Kliofem:

Drugs containing ketoconazole (a fungicide). Taking Kliofem with food and drink

The tablets can be taken with or without food and drink.

Pregnancy and breast-feeding

Do not take Kliofem if you suspect being pregnant, are pregnant or breast-feeding.

Driving and using machines

Kliofem does not affect the use of any machines or the ability to drive safely.

Important information about some of the ingredients of Kliofem:

Kliofem contains lactose monohydrate. If you have an intolerance to some sugars, contact your doctor before taking Kliofem.

How to use Kliofem

Always take Kliofem exactly as your doctor has told you. Check with your doctor or pharmacist if you are unsure.

Take one tablet once a day, at about the same time each day Take the tablet with a glass of water.

Take a tablet every day without stopping. After you have used all 28 tablets in a calendar pack, go straight to using the next pack. See “USER INSTRUCTIONS” at the beginning of the package leaflet. You may start treatment with Kliofem on any convenient day. However, if you are switching from an HRT product where you have a monthly bleed, start your treatment straight after the bleeding has ended. Your doctor should aim to prescribe the lowest dose for the shortest time that gives you relief from your symptoms. Talk to your doctor if your symptoms are not better after three months.

If you take more Kliofem than you should

If you have taken more Kliofem than you should, talk to your doctor or pharmacist. An overdose of Kliofem could make you feel sick or vomit.

If you forget to take Kliofem

If you forget to take your tablet at the usual time, try and take it within the next 12 hours. If more than 12 hours have gone by, start again as normal the next day. Do not take a double dose to make up for a forgotten tablet.

Forgetting a dose may increase the likelihood of breakthrough bleeding and spotting.

If you stop taking Kliofem

If you want to stop taking Kliofem, talk to your doctor first. Your doctor will explain the effects of stopping treatment and discuss other possibilities with you.

If you have any further questions on the use of this product ask your doctor or pharmacist.

Kliofem Side Effects

Like all medicines, Kliofem can have side effects, although not everybody gets them.

Bleeding with Kliofem

Kliofem will not cause regular monthly bleeding, but when first starting the tablets, some women experience slight vaginal bleeding or spotting.

If you get breakthrough bleeding or spotting, it is usually nothing to worry about, especially during the first few months of taking HRT.

But contact your doctor as soon as possible:

If bleeding carries on for more than the first few months If bleeding starts after taking HRT for a while If bleeding continues after stopping HRT.

Your doctor may ask you about any vaginal bleeding with Kliofem at your regular check-ups. You may find it helpful to make a note of any bleedings in a diary.

Very common effects

May affect more than 1 in 10 women

Breast pain or breast tenderness Irregular menstrual periods or excessive bleeding during your periods.

Common effects

May affect up to 1 in 10 women

Fungal infection of the genitals or vaginal inflammation (thrush) Fluid retention Depression or worsening of existing depression Headache Migraine or existing migraine made worse Feeling sick (nausea) Pain, swelling or discomfort of the abdomen (stomach) Back pain Leg cramps Enlargement or swelling of the breasts (breast oedema) Uterine fibroids (benign tumour of the womb): aggravation or re-occurrence Swelling of arms or legs (Peripheral oedema) Weight increase.

Uncommon effects

May affect up to 1 in 100 women

Allergic reaction (hypersensitivity) Nervousness Inflammation of a vein (superficial thrombophlebitiis) Flatulence (wind) or bloating Hair loss or increased facial or body hair or acne Itching Hives (urticaria) Painful periods Excessive growth of the lining of the womb (endometrial hyperplasia) No relief of symptoms (Drug ineffective)

Rare Effects

May affect up to 1 in 1,000 women

Blood clots in the blood vessels of the legs or the lungs (deep vein thrombosis, lung embolism). See also section “Other side effects of HRT” Breast cancer. See also section “Other side effects of HRT”

Very Rare Effects

May affect up to 1 in 10,000 women

Cancer of the lining of the womb (endometrial cancer). See also section “Other side effects of HRT” Insomnia Anxiety Changes in sexual desire Dizziness Visual disturbances Increase in blood pressure or worsening of high blood pressure Heart attack or stroke (see also section “Other side effects of HRT”) Heartburn or vomiting Gallbladder disease Gallstones, aggravation, occurrence or re-occurrence Greasy skin Rash Swelling of the skin or other tissues of sudden onset Vaginal and genital itching Weight decrease. Effects on the skin

Brown patches on the face, skin rashes including red inflammation on the hands or the legs (erythema multiforme), formation of tender, red nodules on the front of the legs/knees (erythema nodosum) or a bruise-like rash.

Other side effects of combined HRT

As well as benefits, HRT has some risks which you need to consider when you’re deciding whether to take it, or whether to carry on taking it.

Effects on your risk of developing cancer

Breast cancer

Women who have breast cancer, or have had breast cancer in the past, should not take HRT.

Taking HRT slightly increases the risk of breast cancer; so does having a later menopause. The risk for a post-menopausal woman taking oestrogen-only HRT for 5 years is about the same as for a woman of the same age who’s still having periods over that time and not taking HRT. The risk for a woman who is taking oestrogen plus progestogen HRT is higher than for oestrogen-only HRT (but oestrogen plus progestogen HRT is beneficial for the endometrium, see ‘Endometrial cancer’ below).

For all kinds of HRT, the extra risk of breast cancer goes up the longer you take it, but returns to normal within about 5 years after stopping HRT.

Your risk of breast cancer is also higher:

If you have a close relative (mother, sister or grandmother) who has had breast cancer If you are seriously overweight.

Compare

Looking at women aged 50 who are not taking HRT - on average, 32 in 1000 will be diagnosed with breast cancer by the time they reach the age of 65.

For women who start taking oestrogen-only HRT at age 50 and take it for 5 years, the figure will be between 33 and 34 in 1000 (i.e. an extra 1-2 cases).

If they take oestrogen-only HRT for 10 years, the figure will be 37 in 1000 (ie an extra 5 cases).

For women who start taking oestrogen plus progestogen HRT at age 50 and take it for 5 years, the figure will be 38 in 1000 (i.e. an extra 6 cases).

If they take oestrogen plus progestogen HRT for 10 years, the figure will be 51 in 1000 (i.e. an extra 19 cases)

If you notice any changes in your breast, such as:

Dimpling of the skin Changes in the nipple Any lumps you can see or feel.

Make an appointment to see your doctor as soon as possible.

Endometrial cancer (cancer of the lining of the womb)

Taking oestrogen-only HRT for a long time can increase the risk of cancer of the lining of the womb (the endometrium). Taking a progestogen as well as the oestrogen helps to lower the extra risk.

If you still have your womb, your doctor may prescribe a progestogen as well as oestrogen. If so, these may be prescribed separately, or as a combined HRT product.

If you have had your womb removed (a hysterectomy), your doctor will discuss with you whether you can safely take oestrogen without a progestogen.

If you’ve had your womb removed because of endometriosis, any endometrium left in your body may be at risk. So your doctor may prescribe HRT that includes a progestogen as well as an oestrogen.

Your product, Kliofem, contains a progestogen.

Compare

Looking at women who still have a uterus and who are not taking HRT – on average 5 in 1000 will be diagnosed with endometrial cancer between the ages of 50 and 65.

For women who take oestrogen-only HRT, the number will be 2 to 12 times higher, depending on the dose and how long you take it. The addition of a progestogen to oestrogen-only HRT substantially reduces the risk of endometrial cancer.

If you get breakthrough bleeding or spotting, it’s usually nothing to worry about, especially during the first few months of taking HRT.

But if the bleeding or spotting:

Carries on for more than the first few months Starts after you’ve been on HRT for a while Carries on even after you’ve stopped taking HRT.

Make an appointment to see your doctor. It could be a sign that your endometrium has become thicker.

Ovarian cancer

Ovarian cancer (cancer of the ovaries) is very rare, but it is serious. It can be difficult to diagnose, because there are often no obvious signs of the disease.

Some studies have indicated that taking HRT for more than 5 years may increase the risk of ovarian cancer.

Effects on your heart or circulation

Blood clots

HRT may increase the risk of blood clots in the veins (also called deep vein thrombosis, or DVT), especially during the first year of taking it.

These blood clots are not always serious, but if one travels to the lungs, it can cause chest pain, breathlessness, collapse or even death. This condition is called pulmonary embolism, or PE.

DVT and PE are examples of a condition called venous thromboembolism, or VTE.

You are more likely to get a blood clot:

If you are seriously overweight If you have had a blood clot before If any of your close family have had blood clots If you have had one or more miscarriages If you have any blood clotting problem that needs treatment with a medicine such as warfarin If you’re off your feet for a long time because of major surgery, injury or illness If you have a rare condition called SLE.

If any of these things apply to you, talk to your doctor to see if you should take HRT.

Compare

Looking at women in their 50s who are not taking HRT - on average, over a 5-year period, 3 in 1000 would be expected to get a blood clot.

For women in their 50s who are taking HRT, the figure would be 7 in 1000.

Looking at women in their 60s who are not taking HRT - on average, over a 5-year period, 8 in 1000 would be expected to get a blood clot.

For women in their 60s who are taking HRT, the figure would be 17 in 1000.

If you get:

Painful swelling in your leg Sudden chest pain Difficulty breathing.

See a doctor as soon as possible and do not take any more HRT until your doctor says you can. These may be signs of a blood clot.

If you’re going to have surgery, make sure your doctor knows about it.

You may need to stop taking HRT about 4 to 6 weeks before the operation, to reduce the risk of a blood clot. Your doctor will tell you when you can start taking HRT again.

Heart disease

HRT is not recommended for women who have heart disease, or have had heart disease recently. If you have ever had heart disease, talk to your doctor to see if you should be taking HRT.

HRT will not help to prevent heart disease.

Studies with one type of HRT (containing conjugated oestrogen plus the progestogen MPA) have shown that women may be slightly more likely to get heart disease during the first year of taking the medication. For other types of HRT, the risk is likely to be similar, although this is not yet certain.

If you get:

A pain in your chest that spreads to your arm or neck.

See a doctor as soon as possible and do not take any more HRT until your doctor says you can. This pain could be a sign of heart disease.

Stroke

Recent research suggests that HRT slightly increases the risk of having a stroke. Other things that can increase the risk of stroke include:

Getting older High blood pressure Smoking Drinking too much alcohol An irregular heartbeat

If you are worried about any of these things, or if you have had a stroke in the past, talk to your doctor to see if you should take HRT.

Compare

Looking at women in their 50s who are not taking HRT - on average, over a 5-year period, 3 in 1000 would be expected to have a stroke.

For women in their 50s who are taking HRT, the figure would be 4 in 1000.

Looking at women in their 60s who are not taking HRT - on average, over a 5-year period, 11 in 1000 would be expected to have a stroke.

For women in their 60s who are taking HRT, the figure would be 15 in 1000.

If you get:

Unexplained migraine-type headaches, with or without disturbed vision.

See a doctor as soon as possible and do not take any more HRT until your doctor says you can. These headaches may be an early warning sign of a stroke

Dementia

There is no evidence that HRT improves processes of knowing, thinking, learning and judging (cognitive function). From a clinical study there is some evidence for an increased risk of dementia among women older than 65 years, who were using another oestrogen/progestogen combination than the one in Kliofem.

It is not known whether this applies to younger women and to women taking other HRT preparations.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

How to store your Kliofem

Keep out of the reach and sight of children.

Do not use Kliofem after the expiry date, which is stated on the label and outer carton after “Exp.”. The expiry date refers to the last day of that month.

Do not store above 25°C.

Do not refrigerate.

Keep the container in the outer carton in order to protect from light.

Medicines should not be disposed of via waste water or household waste.

Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

Further information What Kliofem contains

The active substances are estradiol and norethisterone acetate. Each tablet contains estradiol 2 mg and norethisterone acetate 1 mg.

Other ingredients are: Lactose monohydrate, maize starch, gelatin and magnesium stearate.

The film-coating contains: Hypromellose, triacetin and talc.

What Kliofem looks like and contents of the pack

The film-coated tablets are white, round with a diameter of 6 mm. The tablets are engraved with NOVO 281.

Pack sizes:

28 film-coated tablets

3 x 28 film-coated tablets

Not all pack sizes may be marketed.

Marketing authorisation holder Novo Nordisk Limited Broadfield Park Brighton Road Crawley West Sussex RH11 9RT Manufacturer Novo Nordisk A/S Novo All? DK-2880 Bagsv?rd Denmark

This leaflet was last approved: June 2010

Kliofem is a trademark owned by

Novo Nordisk FemCare AG,

Switzerland

© 1996/2008

Novo Nordisk A/S

User Instructions

How to use the calendar pack

1. Set the day reminder

Turn the inner disc to set the day of the week opposite the little plastic tab.

2. Take the first day’s tablet

Break the plastic tab and tip out the first tablet.

3. Move the dial every day

On the next day simply move the transparent dial clockwise one space as indicated by the arrow. Tip out the next tablet. Remember to take only one tablet once a day.

You can only turn the transparent dial after the tablet in the opening has been removed.

8-2851-01-041-3


read more


Premique 0.625mg / 5mg Coated Tablets


PREMIQUE 0.625mg/5mg Coated Tablets

Conjugated Estrogens and Medroxyprogesterone Acetate

Read all of this leaflet carefully before you start taking this medicine. Keep this leaflet. You may need to read it again. If you have further questions, please ask your doctor or pharmacist. This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours. If any of the side effects gets serious, or you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist. In this leaflet: 1. What Premique is and what it is used for 2. Before you take Premique 3. How to take Premique 4. Possible side effects 5. How to store Premique 6. Further information What Premique Is And What It Is Used For

Premique is one of a group of medicines known as Hormone Replacement Therapy (HRT). It is used to treat some of the symptoms and conditions associated with the menopause. Premique is a period-free HRT (an HRT product where you do not have a monthly bleed).

Your periods will stop once menopause is reached. This change is due to lowered levels of the hormones estrogen and progesterone. You may experience a number of unpleasant symptoms, including hot flushes, night sweats and vaginal dryness, around the time of menopause. Premique can relieve some of these symptoms by replacing some of the lost estrogen.

After the menopause some women may develop bone thinning (osteoporosis). If you are at an increased risk of fractures due to osteoporosis but are unable to take other treatments or if other therapies prove to be ineffective, Premique may also be used for this purpose. Your doctor should discuss all the available options with you.

Before You Take Premique 1 Do not take Premique if: you are allergic (hypersensitive) to conjugated estrogens or medroxyprogesterone acetate or any of the other ingredients of Premique; the ingredients are listed in Section 6 of this leaflet you have or have had breast cancer you have endometrial cancer (cancer of the lining of the womb) or have been told you have another type of estrogen-dependent cancer you have been told you have a blood circulation disorder or have had a blood clot you have a heart condition such as angina or have had a heart attack you have porphyria (a rare inherited metabolic disorder) you have recently had unexpected or very heavy vaginal bleeding you have been told that you have endometrial hyperplasia (abnormal growth of the lining of the womb) you have or have previously had liver disease you are pregnant, or you are breast-feeding.

Before you start taking HRT, your doctor should ask about your own and your family’s medical history. Your doctor may decide to examine your breasts and/or your abdomen, and may do an internal examination — but only if these examinations are necessary for you, or if you have any special concerns.

Once you’ve started on HRT, you should see your doctor for regular check-ups (at least once a year). At these check-ups, your doctor may discuss with you the benefits and risks of continuing to take HRT.

You are advised to:

go for regular breast screening and cervical smear tests regularly check your breasts for any changes such as dimpling of the skin, changes in the nipple, or any lumps you can see or feel.

Some diseases may be made worse by HRT. Therefore, if you have or have ever had any of the following remind your doctor as he or she may want to monitor you more closely:

uterine fibroids or endometriosis risk factors for blood clots (see section 2.2 - Blood Clots for more detail) a close relative who has had breast cancer or an estrogen dependent cancer, such as cancer of the womb or ovaries (see section 2.3Effects on your risk of developing cancer for more detail) high blood pressure heart disease (see section 2.2Heart Disease for more detail) liver disease (e.g. liver adenoma) kidney disease diabetes gallbladder disease or gallstones migraine systemic lupus erythematosus (SLE – a rare chronic inflammatory disease) epilepsy asthma otosclerosis (hearing loss due to a problem with the bones in your ear) low blood calcium levels (hypocalcaemia) high levels of fatty substances in the blood (hypertriglyceridaemia).

If there is a change in any of the above conditions whilst taking Premique tell your doctor.

As well as benefits, HRT has some risks which you need to consider when you’re deciding whether to take it, or whether to carry on taking it.

2 Effects on your heart or circulation:

Heart Disease

HRT is not recommended for women who have heart disease, or have had heart disease recently. If you have ever had heart disease, talk to your doctor to see if you should be taking HRT.

HRT will not help to prevent heart disease.

Studies with one type of HRT (containing conjugated estrogens plus the progestogen MPA) have shown that women may be slightly more likely to get heart disease during the first year of taking the medication. For other types of HRT, the risk is likely to be similar, although this is not yet certain.

If you get:

a pain in your chest that spreads to your arm or neck See a doctor as soon as possible and do not take any more HRT until your doctor says you can. This pain could be a sign of heart disease.

Stroke

Recent research suggests that HRT slightly increases the risk of having a stroke.

Other things that can increase the risk of stroke include:

getting older high blood pressure smoking drinking too much alcohol an irregular heartbeat.

If you are worried about any of these things, or if you have had a stroke in the past, talk to your doctor to see if you should take HRT.

Looking at women in their 50s who are not taking HRT — on average, over a 5-year period, 3 in 1000 would be expected to have a stroke.

For women in their 50s who are taking HRT, the figure would be 4 in 1000.

Looking at women in their 60s who are not taking HRT — on average, over a 5-year period, 11 in 1000 would be expected to have a stroke.

For women in their 60s who are taking HRT, the figure would be 15 in 1000.

If you get:

unexplained migraine-type headaches, with or without disturbed vision See a doctor as soon as possible and do not take any more HRT until your doctor says you can. These headaches may be an early warning sign of a stroke.

Blood Clots

HRT may increase the risk of blood clots in the veins (also called deep vein thrombosis, or DVT), especially during the first year of taking it.

These blood clots are not always serious, but if one travels to the lungs, it can cause chest pain, breathlessness, collapse or even death. This condition is called pulmonary embolism, or PE.

DVT and PE are examples of a condition called venous thromboembolism, or VTE.

You are more likely to get a blood clot:

if you are seriously overweight if you have had a blood clot before if any of your close family have had blood clots if you have had one or more miscarriages if you have any blood clotting problem that needs treatment with a medicine such as warfarin if you’re off your feet for a long time because of major surgery, injury or illness if you have a rare condition called SLE (systemic lupus erythematosus).

If any of these things apply to you, talk to your doctor to see if you should take HRT.

Looking at women in their 50s who are not taking HRT — on average, over a 5-year period, 3 in 1000 would be expected to get a blood clot.

For women in their 50s who are taking HRT, the figure would be 7 in 1000.

Looking at women in their 60s who are not taking HRT — on average, over a 5-year period, 8 in 1000 would be expected to get a blood clot.

For women in their 60s who are taking HRT, the figure would be 17 in 1000.

If you get:

painful swelling in your leg sudden chest pain difficulty breathing See a doctor as soon as possible and do not take any more HRT until your doctor says you can. These may be signs of a blood clot.

If you’re going to have surgery, make sure your doctor knows about it. You may need to stop taking HRT about 4 to 6 weeks before the operation, to reduce the risk of a blood clot. Your doctor will tell you when you can start taking HRT again.

3 Effects on your risk of developing cancer:

Breast Cancer

Women who have breast cancer, or have had breast cancer in the past, should not take HRT.

Taking HRT slightly increases the risk of breast cancer; so does having a later menopause. The risk for a post-menopausal woman taking estrogen-only HRT for 5 years is about the same as for a woman the same age who’s still having periods over that time and not taking HRT. The risk for a woman who is taking estrogen plus progestogen HRT is higher than for estrogen-only HRT (but estrogen plus progestogen HRT is beneficial for the endometrium, see Endometrial Cancer below).

For all kinds of HRT, the extra risk of breast cancer goes up the longer you take it, but returns to normal within about 5 years after stopping.

Your risk of breast cancer is also higher:

if you have a close relative (mother, sister or grandmother) who has had breast cancer if you are seriously overweight.

Looking at women aged 50 who are not taking HRT – on average, 32 in 1000 will be diagnosed with breast cancer by the time they reach the age of 65.

For women who start taking estrogen-only HRT at age 50 and take it for 5 years, the figure will be between 33 and 34 in 1000 (i.e. an extra 1-2 cases).

If they take estrogen-only HRT for 10 years, the figure will be 37 in 1000 (i.e. an extra 5 cases).

For women who start taking estrogen plus progestogen HRT at age 50 and take it for 5 years, the figure will be 38 in 1000 (i.e. an extra 6 cases).

If they take estrogen plus progestogen HRT for 10 years, the figure will be 51 in 1000 (i.e. an extra 19 cases).

If you notice any changes in your breast, such as:

dimpling of the skin changes in the nipple any lumps you can see or feel Make an appointment to see your doctor as soon as possible.

Endometrial Cancer (cancer of the lining of the womb)

Taking estrogen-only HRT for a long time can increase the risk of cancer of the lining of the womb (the endometrium). Taking a progestogen as well as the estrogen helps to lower the extra risk.

If you still have your womb, your doctor may prescribe a progestogen as well as estrogen. If so, these may be prescribed separately, or as a combined HRT product.

If you have had your womb removed (a hysterectomy), your doctor will discuss with you whether you can safely take estrogen without a progestogen.

If you’ve had your womb removed because of endometriosis, any endometrium left in your body may be at risk. So your doctor may prescribe HRT that includes a progestogen as well as an estrogen.

Your product, Premique, contains a progestogen.

Looking at women who still have a uterus and who are not taking HRT – on average 5 in 1000 will be diagnosed with endometrial cancer between the ages of 50 and 65.

For women who take estrogen-only HRT, the number will be 2 to 12 times higher, depending on the dose and how long they take it.

The addition of a progestogen to estrogen-only HRT substantially reduces the risk of endometrial cancer.

If you get breakthrough bleeding or spotting, it’s usually nothing to worry about, especially during the first few months of taking HRT.

But if the bleeding or spotting:

carries on for more than the first few months starts after you’ve been on HRT for a while carries on even after you’ve stopped taking HRT Make an appointment to see your doctor. It could be a sign that your endometrium has become thicker.

Ovarian Cancer

Ovarian cancer (cancer of the ovaries) is very rare, but it is serious. It can be difficult to diagnose, because there are often no obvious signs of the disease.

Some studies have indicated that taking estrogen-only HRT for more than 5 years may increase the risk of ovarian cancer. It is not yet known whether other kinds of HRT increase the risk in the same way.

4 Other Conditions

HRT will not help prevent memory loss. In one study of women who started using combined HRT after the age of 65, a small increase in the risk of dementia was observed.

Women with hypertriglyceridaemia (high levels of fatty substances in the blood) may experience large increases of their plasma triglycerides, which can lead to inflammation of the pancreas (pancreatitis). Symptoms of pancreatitis include sudden sharp abdominal pains, abdominal swelling, fever and feeling or being sick.

If you are taking thyroid hormone replacement therapy (e.g. thyroxine), your doctor may monitor your thyroid function more often when you start treatment.

HRT may affect some medical tests. If you visit a hospital or clinic for any medical tests, you should tell the doctor concerned that you are taking HRT.

5 Taking other medicines

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

In particular tell your doctor if you are taking:

an anticonvulsant (used to treat epilepsy e.g. phenobarbital, phenytoin, carbamazepine) an anti-infective (e.g. rifampicin, rifabutin, nevirapine, efavirenz, erythromycin, ketoconazole, ritonavir, nelfinavir) a herbal preparation such as St. John’s wort (Hypericum perforatum) metyrapone (most commonly used in the treatment of Cushing’s syndrome) aminoglutethimide (most commonly used in the treatment of breast cancer and Cushing’s syndrome).

The way that Premique works may be altered if other medicines are used at the same time.

6 Pregnancy and breast-feeding

You should stop taking Premique and tell your doctor immediately if you know or suspect you are pregnant, or if you are breast-feeding.

Premique is not a contraceptive. It is important that you use a reliable form of non-hormonal contraception (e.g. condom or diaphragm) if there is any possibility that you may still become pregnant. You should discuss this with your doctor.

7 Driving and using machines

There is no evidence to suggest that Premique will affect your ability to drive or to operate machinery.

8 Important information about some of the ingredients in Premique

Premique contains lactose and sucrose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

How To Take Premique 1 Instructions for proper use

Always take Premique exactly as your doctor has told you. You should check with your doctor or pharmacist if you are unsure.

The usual dose is one tablet every day.

Your doctor will aim to give you the lowest dose for the shortest time to treat your symptoms.

Take your tablet at the same time each day as this will help to remind you to take your medicine.

If you are not currently taking HRT or you are taking another period-free HRT, you may start your first pack of Premique at any convenient time.

If you are changing from an HRT product that gives you a monthly bleed, start Premique the day after you finish the course of the previous product, unless instructed otherwise by your doctor.

Begin your pack of Premique by taking the first tablet marked for that day of the week. Continue to take one tablet each day following the arrows until all 28 tablets have been taken.

While you are taking Premique you will have no tablet-free days. You should start your next pack the day after you finish the previous one.

Premique does not cause periods. However, you may experience some irregular bleeding or light bleeding (spotting) during your first few months of taking Premique. If the bleeding is troublesome, or continues beyond the first 3 months of treatment you should discuss this with your doctor (see section titled Endometrial Cancer above).

Do not try to take off the coating, divide or crush the tablets as this could affect the way Premique works.

2 If you take more Premique than you should

If you take too many tablets don’t worry. You may feel some nausea (sickness), breast tenderness, dizziness, abdominal pain, drowsiness, fatigue or experience a short period of vaginal bleeding, but it is unlikely that serious problems will result. If you are concerned talk to your doctor or pharmacist.

3 If you forget to take Premique

If you forget to take a tablet don’t worry. Take it as soon as you remember and then carry on taking the remaining tablets at the usual time.

If more than one tablet has been forgotten, do not take extra to try to make up for the missed tablets.

Missed tablets may cause a short period of light bleeding in women who have not had a hysterectomy.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

Possible Side Effects

Like all medicines, Premique can cause side effects, although not everybody gets them.

1 Serious side effects

Stop taking Premique and tell your doctor immediately if you:

have an allergic reaction, signs of which include rash, itching, shortness of breath, difficulty breathing and a swollen face experience a migraine type headache (typically a throbbing headache and nausea preceded by visual disturbances) for the first time develop signs of jaundice (yellowing of the skin or the whites of the eyes) become pregnant experience a significant increase in your blood pressure develop a contraindication i.e. circumstances which make treatment inadvisable (see Section 2 - Before you take Premique).

Do not take any more tablets until your doctor says you can.

HRT can also increase the risk of heart disease, stroke, blood clots, breast cancer, endometrial cancer and ovarian cancer. Please see Section 2 - Before you take Premique.

2 Other side effects

Very common (affect more than 1 in 10 women)

breast pain

Common (affect less than 1 in 10 women)

breakthrough bleeding or spotting, vaginal inflammation, period pain breast tenderness, swollen breasts, nipple discharge depression muscle and joint aches, leg cramps weight change (increase or decrease) changes in your triglyceride levels (fatty substances in the blood)

Uncommon (affect less than 1 in 100 women)

changes in menstrual flow, vaginal discharge thrush nausea, bloating, abdominal pain headache, migraine blood clots in the veins dizziness changes in mood including anxiety changes in your interest in sex (increased or decreased libido) visible swelling of the face or ankles itchiness, acne difficulty wearing contact lenses gallbladder disease (e.g. gallstones) hair loss

Rare (affect less than 1 in 1000 women)

vomiting changes in breast tissue, milky secretion from the breasts irritability allergic reactions including swelling, rash or red patches on the skin increase in hair growth an intolerance to glucose a worsening of asthma increased size of fibroids ovarian cancer worsening of epilepsy heart attack, stroke inflammation of veins just under the skin inflammation of the pancreas irregular dark spots (usually on the face)

Very rare (affect less than 1 in 10000 women)

jaundice (e.g. yellowing of the skin) a worsening of chorea (an existing neurological disorder characterised by involuntary spasmodic movements of the body) a worsening of hypocalcaemia (low blood levels of calcium) blurred vision or loss of vision worsening of porphyria (a rare inherited metabolic disorder) growth of benign liver tumours

These side effects are usually temporary and should get better over time.

Other side effects that may occur while taking an estrogen-progesterone combined HRT are:

memory loss (dementia)

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

How To Store Premique

Keep out of the reach and sight of children.

Do not use this medicine after the expiry date stated on the carton and blister. The expiry date refers to the last day of the month.

Do not store above 25°C. Keep the blister in the outer carton to protect from light.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

Further Information 1 What Premique contains The active ingredients are an estrogen (conjugated estrogens) and a progestogen (medroxyprogesterone acetate).

Each blister pack contains 28 oval coated tablets, each tablet contains 0.625mg of conjugated estrogens and 5mg of medroxyprogesterone acetate (MPA). The tablets are light blue coloured and marked with “ 0.625/5”.

The other ingredients are calcium phosphate tribasic, calcium sulphate, microcrystalline cellulose, carnauba wax, glyceryl mono-oleates, lactose, magnesium stearate, methylcellulose, macrogol, pharmaceutical glaze, povidone, sucrose, titanium dioxide (E171), stearic acid and colour (E132, indigo carmine) and edible ink containing iron oxide black (E172), shellac, N-Butyl alcohol, propylene glycol and ethyl acetate. The inks and dyes used to coat your tablets are approved for use as food colourings. 2 What Premique looks like and contents of the pack

Your Premique carton contains either one or three blisters, each containing 28 tablets.

Not all pack sizes may be marketed.

The marketing authorisation holder is

John Wyeth & Brother Ltd trading as Wyeth Pharmaceuticals Huntercombe Lane South Taplow Maidenhead Berkshire SL6 0PH

The manufacturer is

Wyeth Medica Ireland Little Connell Newbridge County Kildare Republic of Ireland

This leaflet applies to Premique tablets only.

This leaflet was last approved in 04/2010

Doc ID 60103 (combined from doc id56233 and 51576)


read more


Fluorouracil Cream



Fluorouracil Topical Cream USP, 5%

FOR TOPICAL USE ONLY
NOT FOR OPHTHALMIC, ORAL, OR INTRAVAGINAL USE.

Fluorouracil Cream Description

Fluorouracil Topical Cream is a topical preparation containing the fluorinated pyrimidine 5-fluorouracil, an antineoplastic antimetabolite.

Fluorouracil Topical Cream contains 5% w/w of Fluorouracil USP in a cream base consisting of methylparaben, polysorbate 60, propylene glycol, propylparaben, purified water, stearyl alcohol and white petrolatum.

Chemically, fluorouracil is 5-fluoro-2,4(1H,3H)-pyrimidinedione. It is a white to practically white, crystalline powder which is sparingly soluble in water and slightly soluble in alcohol. One gram of fluorouracil is soluble in 100 mL of propylene glycol. The molecular weight of 5-fluorouracil is 130.08 and the structural formula is:

Fluorouracil Cream - Clinical Pharmacology

There is evidence that the metabolism of fluorouracil in the anabolic pathway blocks the methylation reaction of deoxyuridylic acid to thymidylic acid. In this manner fluorouracil interferes with the synthesis of deoxyribonucleic acid (DNA) and to a lesser extent inhibits the formation of ribonucleic acid (RNA). Since DNA and RNA are essential for cell division and growth, the effect of fluorouracil may be to create a thymine deficiency which provokes unbalanced growth and death of the cell. The effects of DNA and RNA deprivation are most marked on those cells which grow more rapidly and take up fluorouracil at a more rapid rate. The catabolic metabolism of fluorouracil results in degradation products (eg, CO2, urea, ?-fluoro-?-alanine) which are inactive.

Systemic absorption studies of topically applied fluorouracil have been performed on patients with actinic keratoses using tracer amounts of 14C-labeled fluorouracil added to a 5% preparation. All patients had been receiving nonlabeled fluorouracil until the peak of the inflammatory reaction occurred (2 to 3 weeks), ensuring that the time of maximum absorption was used for measurement. One gram of labeled preparation was applied to the entire face and neck and left in place for 12 hours. Urine samples were collected. At the end of 3 days, the total recovery ranged between 0.48% and 0.94% with an average of 0.76%, indicating that approximately 5.98% of the topical dose was absorbed systemically. If applied twice daily, this would indicate systemic absorption of topical fluorouracil to be in the range of 5 to 6 mg per daily dose of 100 mg. In an additional study, negligible amounts of labeled material were found in plasma, urine and expired CO2 after 3 days of treatment with topically applied 14C-labeled fluorouracil.

Indications and Usage for Fluorouracil Cream

Fluorouracil is recommended for the topical treatment of multiple actinic or solar keratoses. In the 5% strength it is also useful in the treatment of superficial basal cell carcinomas when conventional methods are impractical, such as with multiple lesions or difficult treatment sites. Safety and efficacy in other indications have not been established.

The diagnosis should be established prior to treatment, since this method has not been proven effective in other types of basal cell carcinomas. With isolated, easily accessible basal cell carcinomas, surgery is preferred since success with such lesions is almost 100%. The success rate with Fluorouracil Cream and Solution is approximately 93%, based on 113 lesions in 54 patients. Twenty-five lesions treated with the solution produced 1 failure and 88 lesions treated with the cream produced 7 failures.

Contraindications

Fluorouracil may cause fetal harm when administered to a pregnant woman.

There are no adequate and well-controlled studies in pregnant women with either the topical or the parenteral forms of fluorouracil. One birth defect (cleft lip and palate) has been reported in the newborn of a patient using Fluorouracil as recommended. One birth defect (ventricular septal defect) and cases of miscarriage have been reported when Fluorouracil was applied to mucous membrane areas. Multiple birth defects have been reported in a fetus of a patient treated with intravenous fluorouracil.

Animal reproduction studies have not been conducted with Fluorouracil. Fluorouracil administered parenterally has been shown to be teratogenic in mice, rats, and hamsters when given at doses equivalent to the usual human intravenous dose; however, the amount of fluorouracil absorbed systemically after topical administration to actinic keratoses is minimal (see CLINICAL PHARMACOLOGY). Fluorouracil exhibited maximum teratogenicity when given to mice as single intraperitoneal injections of 10 to 40 mg/kg on Day 10 or 12 of gestation. Similarly, intraperitoneal doses of 12 to 37 mg/kg given to rats between Days 9 and 12 of gestation and intramuscular doses of 3 to 9 mg/kg given to hamsters between Days 8 and 11 of gestation were teratogenic and/or embryotoxic (ie, resulted in increased resorptions or embryolethality). In monkeys, divided doses of 40 mg/kg given between Days 20 and 24 of gestation were not teratogenic. Doses higher than 40 mg/kg resulted in abortion.

Fluorouracil should not be used in patients with dihydropyrimidine dehydrogenase (DPD) enzyme deficiency. A large percentage of fluorouracil is catabolized by the DPD enzyme. DPD enzyme deficiency can result in shunting of fluorouracil to the anabolic pathway, leading to cytotoxic activity and potential toxicities.

Fluorouracil is contraindicated in women who are or may become pregnant during therapy. If this drug is used during pregnancy, or if the patient becomes pregnant while using this drug, the patient should be apprised of the potential hazard to the fetus.

Fluorouracil is also contraindicated in patients with known hypersensitivity to any of its components.

Warnings

Application to mucous membranes should be avoided due to the possibility of local inflammation and ulceration. Additionally, cases of miscarriage and a birth defect (ventricular septal defect) have been reported when Fluorouracil was applied to mucous membrane areas during pregnancy.

Occlusion of the skin with resultant hydration has been shown to increase percutaneous penetration of several topical preparations. If any occlusive dressing is used in treatment of basal cell carcinoma, there may be an increase in the severity of inflammatory reactions in the adjacent normal skin. A porous gauze dressing may be applied for cosmetic reasons without increase in reaction.

Exposure to ultraviolet rays should be minimized during and immediately following treatment with Fluorouracil because the intensity of the reaction may be increased.

Patients should discontinue therapy with Fluorouracil if symptoms of DPD enzyme deficiency develop (see CONTRAINDICATIONS section).

Rarely, life-threatening toxicities such as stomatitis, diarrhea, neutropenia, and neurotoxicity have been reported with intravenous administration of fluorouracil in patients with DPD enzyme deficiency. One case of life- threatening systemic toxicity has been reported with the topical use of Fluorouracil in a patient with DPD enzyme deficiency. Symptoms included severe abdominal pain, bloody diarrhea, vomiting, fever, and chills. Physical examination revealed stomatitis, erythematous skin rash, neutropenia, thrombocytopenia, inflammation of the esophagus, stomach, and small bowel. Although this case was observed with 5% Fluorouracil Cream, it is unknown whether patients with profound DPD enzyme deficiency would develop systemic toxicity with lower concentrations of topically applied fluorouracil.

Precautions General

There is a possibility of increased absorption through ulcerated or inflamed skin.

Information for Patients

Patients should be forewarned that the reaction in the treated areas may be unsightly during therapy and, usually, for several weeks following cessation of therapy. Patients should be instructed to avoid exposure to ultraviolet rays during and immediately following treatment with Fluorouracil because the intensity of the reaction may be increased. If Fluorouracil is applied with the fingers, the hands should be washed immediately afterward. Fluorouracil should not be applied on the eyelids or directly into the eyes, nose or mouth because irritation may occur.

Laboratory Tests

Solar keratoses which do not respond should be biopsied to confirm the diagnosis. Follow-up biopsies should be performed as indicated in the management of superficial basal cell carcinoma.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Adequate long-term studies in animals to evaluate carcinogenic potential have not been conducted with fluorouracil. Studies with the active ingredient of Fluorouracil, 5-fluorouracil, have shown positive effects in in vitro tests for mutagenicity and on impairment of fertility.

5-Fluorouracil was positive in three in vitro cell neoplastic transformation assays. In the C3H/10T1/2 clone 8 mouse embryo cell system, the resulting morphologically transformed cells formed tumors when inoculated into immunosuppressed syngeneic mice.

While no evidence for mutagenic activity was observed in the Ames test (3 studies), fluorouracil has been shown to be mutagenic in the survival count rec-assay with Bacillus subtilis and in the Drosophila wing-hair spot test. Fluorouracil produced petite mutations in Saccharomyces cerevisiae and was positive in the micronucleus test (bone marrow cells of male mice).

Fluorouracil was clastogenic in vitro (ie, chromatid gaps, breaks and exchanges) in Chinese hamster fibroblasts at concentrations of 1.0 and 2.0 µg/mL and has been shown to increase sister chromatid exchange in vitro in human lymphocytes. In addition, 5-fluorouracil has been reported to produce an increase in numerical and structural chromosome aberrations in peripheral lymphocytes of patients treated with this product.

Doses of 125 to 250 mg/kg, administered intraperitoneally, have been shown to induce chromosomal aberrations and changes in chromosome organization of spermatogonia in rats. Spermatogonial differentiation was also inhibited by fluorouracil, resulting in transient infertility. However, in studies with a strain of mouse which is sensitive to the induction of sperm head abnormalities after exposure to a range of chemical mutagens and carcinogens, fluorouracil was inactive at oral doses of 5 to 80 mg/kg/day. In female rats, fluorouracil administered intraperitoneally at doses of 25 and 50 mg/kg during the preovulatory phase of oogenesis significantly reduced the incidence of fertile matings, delayed the development of preimplantation and postimplantation embryos, increased the incidence of preimplantation lethality and induced chromosomal anomalies in these embryos. Single dose intravenous and intraperitoneal injections of 5-fluorouracil have been reported to kill differentiated spermatogonia and spermatocytes (at 500 mg/kg) and to produce abnormalities in spermatids (at 50 mg/kg) in mice.

Pregnancy Teratogenic Effects Pregnancy Category X

See CONTRAINDICATIONS section.

Nursing Mothers

It is not known whether Fluorouracil is excreted in human milk. Because there is some systemic absorption of fluorouracil after topical administration (see CLINICAL PHARMACOLOGY), because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue use of the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness in children have not been established.

Adverse Reactions

The most frequent adverse reactions to Fluorouracil occur locally and are often related to an extension of the pharmacological activity of the drug. These include burning, crusting, allergic contact dermatitis, erosions, erythema, hyperpigmentation, irritation, pain, photosensitivity, pruritus, scarring, rash, soreness and ulceration. Ulcerations, other local reactions, cases of miscarriage and a birth defect (ventricular septal defect) have been reported when Fluorouracil was applied to mucous membrane areas. Leukocytosis is the most frequent hematological side effect.

Although a causal relationship is remote, other adverse reactions which have been reported infrequently are:

Central Nervous System: Emotional upset, insomnia, irritability.

Gastrointestinal: Medicinal taste, stomatitis.

Hematological: Eosinophilia, thrombocytopenia, toxic granulation.

Integumentary: Alopecia, blistering, bullous pemphigoid, discomfort, ichthyosis, scaling, suppuration, swelling, telangiectasia, tenderness, urticaria, skin rash.

Special Senses: Conjunctival reaction, corneal reaction, lacrimation, nasal irritation.

Miscellaneous: Herpes simplex.

Overdosage

There have been no reports of overdosage with Fluorouracil.

The oral LD50 for the 5% topical cream was 234 mg/kg in rats and 39 mg/kg in dogs. These doses represented 11.7 and 1.95 mg/kg of fluorouracil, respectively. Studies with a 5% topical solution yielded an oral LD50 of 214 mg/kg in rats and 28.5 mg/kg in dogs, corresponding to 10.7 and 1.43 mg/kg of fluorouracil, respectively. The topical application of the 5% cream to rats yielded an LD50 of greater than 500 mg/kg.

Fluorouracil Cream Dosage and Administration

When Fluorouracil is applied to a lesion, a response occurs with the following sequence: erythema, usually followed by vesiculation, desquamation, erosion and reepithelialization.

Fluorouracil should be applied preferably with a nonmetal applicator or suitable glove. If Fluorouracil is applied with the fingers, the hands should be washed immediately afterward.

Actinic or Solar Keratosis

Apply cream twice daily in an amount sufficient to cover the lesions. Medication should be continued until the inflammatory response reaches the erosion stage, at which time use of the drug should be terminated. The usual duration of therapy is from 2 to 4 weeks. Complete healing of the lesions may not be evident for 1 to 2 months following cessation of Fluorouracil therapy.

Superficial Basal Cell Carcinomas

Only the 5% strength is recommended. Apply cream twice daily in an amount sufficient to cover the lesions. Treatment should be continued for at least 3 to 6 weeks. Therapy may be required for as long as 10 to 12 weeks before the lesions are obliterated. As in any neoplastic condition, the patient should be followed for a reasonable period of time to determine if a cure has been obtained.

How is Fluorouracil Cream Supplied

Fluorouracil Cream is supplied in a 5 g tube (NDC 51672-4118-5), 25 g tube (NDC 51672-4118-2) and 40 g tube (NDC 51672-4118-6).

Store at 20°- 25°C (68°F – 77°F) [see USP Controlled Room Temperature].

Mfr. by: Taro Pharmaceutical Industries Ltd., Haifa Bay 26110, Israel
Dist. by: Taro Pharmaceuticals U.S.A. Inc., Hawthorne, NY 10532

Issued: February, 2010
70715-0210-1
582

PRINCIPAL DISPLAY PANEL - 40 g Tube Carton

NDC 51672-4118-6

40 g

Fluorouracil
Topical Cream USP, 5%

FOR TOPICAL DERMATOLOGICAL USE ONLY.
NOT FOR OPHTHALMIC USE OR INTRAVAGINAL USE.

Rx only

Keep this and all medications out of the reach of children.

TARO


FLUOROURACIL 
fluorouracil  cream Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 52549-4118 Route of Administration TOPICAL DEA Schedule      Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Fluorouracil (Fluorouracil) Fluorouracil 50 mg  in 1 g Inactive Ingredients Ingredient Name Strength petrolatum   stearyl alcohol   propylene glycol   polysorbate 60   methylparaben   propylparaben   water   Product Characteristics Color WHITE Score      Shape Size Flavor Imprint Code Contains          Packaging # NDC Package Description Multilevel Packaging 1 52549-4118-5 5 g In 1 TUBE None 2 52549-4118-2 1 TUBE In 1 CARTON contains a TUBE 2 25 g In 1 TUBE This package is contained within the CARTON (52549-4118-2) 3 52549-4118-6 1 TUBE In 1 CARTON contains a TUBE 3 40 g In 1 TUBE This package is contained within the CARTON (52549-4118-6)
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA090368 03/05/2010
Labeler - Taro Pharmaceutical Industries Ltd. (600072078) Establishment Name Address ID/FEI Operations Taro Pharmaceutical Industries Ltd. 600072078 ANALYSIS, MANUFACTURE Revised: 08/2010Taro Pharmaceutical Industries Ltd. More Fluorouracil Cream resources Fluorouracil Cream Use in Pregnancy & Breastfeeding Fluorouracil Cream Support Group 23 Reviews for Fluorouracil - Add your own review/rating Compare Fluorouracil Cream with other medications Actinic Keratosis Basal Cell Carcinoma Skin Cancer
read more


Progynova TS 50


Due to regulatory changes, the content of the following Patient Information Leaflet may vary from the one found in your medicine pack. Please compare the 'Leaflet prepared/revised date' towards the end of the leaflet to establish if there have been any changes.

If you have any doubts or queries about your medication, please contact your doctor or pharmacist.

Progynova TS 50 micrograms/24 hours transdermal patch

(estradiol)

Please read all of this booklet carefully before you start taking your medicine Keep this booklet as you may need to read it again. If you have further questions, please ask your doctor or your pharmacist. This medicine has been prescribed for you personally. It is not suitable for all women, so you should not give it to anyone else as it may harm them. This medicine is called ‘Progynova TS 50 micrograms/24 hours transdermal patch’ but will be referred to as ‘Progynova TS 50’ throughout this booklet. Contents What Progynova TS 50 is and what it is used for What does Progynova TS 50 contain? What kind of medicine is Progynova TS 50? What is Progynova TS 50 used for?
Before you use Progynova TS 50
Reasons for not using Progynova TS 50
What you should know before using Progynova TS 50 Medical check-ups Effects on your heart or circulation Effects on your risk of developing cancer Other important information What to do if you are taking other medicines at the same time as Progynova TS 50
How to use Progynova TS 50 To apply Progynova TS 50 What to do if a patch falls off What to do if you forget a patch What to do if you use too many patches
Possible side effects
Reasons for stopping Progynova TS 50
How to store Progynova TS 50 What Progynova TS 50 is and what it is used for

The name of your treatment is Progynova TS 50.

What does Progynova TS 50 contain?

Progynova patches are oval transparent patches with a self-adhesive backing, which can be stuck to the skin.

Progynova TS 50 is a patch with an area of 12.5 square centimetres containing 3.8 milligrams of estradiol, an oestrogen, (formed from 3.9 milligrams estradiol hemihydrate). Your body will absorb about 50 micrograms of estradiol each day whilst you are wearing a Progynova TS 50 patch.

Inactive ingredients: ethyl oleate, isopropyl myristate and glycerol monolaurate. The adhesive system is an acrylate/acrylamide/vinyl acetate copolymer.

Packs containing either 4 or 12 patches are available. Each sealed pouch contains one Progynova TS 50 patch.

What kind of medicine is Progynova TS 50?

Progynova TS 50 patches are a form of oestrogen replacement therapy.

What is Progynova TS 50 used for?

Progynova TS 50 is used to treat symptoms of the menopause in women who are at least one year past their last menstrual period. The patches contain the hormone oestrogen which is absorbed through your skin and into the blood stream. They can therefore relieve the symptoms caused by the loss of your own oestrogen. Your doctor will aim to prescribe the lowest dose that controls your symptoms.

Thinning of the bones (osteoporosis) can occur after the menopause. In some women this can lead to fractures of the wrist, spine or hip in later life. You may be able to use Progynova TS 50 to prevent this if you are unable to take other treatments or they haven’t worked for you. Your doctor will be able to advise you further.

Because it only contains one of the female sex hormones, Progynova TS 50 is not suitable to be used alone for women who have not previously had a hysterectomy. You will need to take another hormone, progestogen, as well as Progynova TS 50 if this is the case. Your doctor will be able to advise you about this. (See “Effects on your risk of developing cancer” for more information).

The product licence for Progynova TS 50 is held by: Bayer plc Bayer House Strawberry Hill Newbury Berkshire RG14 1JA

Product Licence number:

PL 00010/0560

Progynova TS 50 is made by: 3M Pharmaceuticals Northridge California USA

Batch release in the EU by

Schering GmbH and Co. Productions KG Germany Before you use Progynova TS 50 Reasons for not using Progynova TS 50

You must not use Progynova TS 50 if you have any of the following:

a blood clot in a vein in your leg or anywhere else (a “deep vein thrombosis”) or a blood clot that has travelled to your lung or another part of the body (an “embolus”) or have had one of these in the past angina (severe chest pain), or if you have recently had a heart attack the rare inherited disorder porphyria a hormone dependent tumour e.g. cancer of the lining of the womb (endometrial cancer) breast cancer, or have had this in the past if you have an allergy to any of the ingredients. Tell your doctor if: you are pregnant or breast feeding you have liver disease or have had this in the past you have irregular or unusually heavy periods you have endometrial hyperplasia (changes to the lining of the womb which may cause heavy vaginal bleeding) or have had this in the past

as these may mean that Progynova TS 50 is not suitable for you.

What you should know before using Progynova TS 50

As well as benefits, HRT has some risks which you need to consider when you’re deciding whether to take it, or whether to carry on taking it.

Medical check-ups

Before you start taking HRT, your doctor should ask about your own and your family’s medical history. Your doctor may decide to examine your breasts and/or your abdomen, and may do an internal examination — but only if these examinations are necessary for you, or if you have any special concerns.

Once you’ve started on HRT, you should see your doctor for regular check-ups (at least once a year). At these check-ups, your doctor may discuss with you the benefits and risks of continuing to take HRT.

Make sure you:

go for regular breast screening and cervical smear tests regularly check your breasts for any changes such as dimpling of the skin, changes in the nipple, or any lumps you can see or feel.

Certain diseases sometimes get worse when you are taking hormone replacement therapy.

So tell your doctor if you suffer from: fibroids of the womb endometriosis (lining of the womb growing in the wrong place causing pain or bleeding) risk factors for getting blood clots (see “Effects on your heart or circulation – blood clots” for more information) risk factors for hormone dependent tumours (see “Effects on your risk of developing cancer high blood pressure diabetes gall stones migraine or severe headaches systemic lupus erythematosus – SLE (a disease affecting the skin all over the body) epilepsy asthma inherited deafness (otosclerosis) heart or kidney problems a blood-fat disorder called hypertriglyceridaemia hereditary angioedema (episodes of swelling of body parts)

These may mean that your doctor will need to check you more closely.

If you are not sure whether any of these apply to you, ask your doctor. If any of these conditions appear during your use of Progynova TS 50, contact your doctor for advice. Effects on your heart or circulation

Heart disease

HRT is not recommended for women who have heart disease, or have had heart disease recently. If you have ever had heart disease, talk to your doctor to see if you should be taking HRT. HRT will not help to prevent heart disease.

Studies with one type of HRT (containing conjugated oestrogen plus the progestogen MPA) have shown that women may be slightly more likely to get heart disease during the first year of taking the medication. For other types of HRT, the risk is likely to be similar, although this is not yet certain.

If you get:

a pain in your chest that spreads to your arm or neck See a doctor as soon as possible and do not take any more HRT until your doctor says you can. This pain could be a sign of heart disease.

Stroke

Recent research suggests that HRT slightly increases the risk of having a stroke. Other things that can increase the risk of stroke include:

getting older high blood pressure smoking drinking too much alcohol an irregular heartbeat.

If you are worried about any of these things, or if you have had a stroke in the past, talk to your doctor to see if you should take HRT.

Compare

Looking at women in their 50s who are not taking HRT — on average, over a 5-year period, 3 in 1000 would be expected to have a stroke.

For women in their 50s who are taking HRT, the figure would be 4 in 1000.

Looking at women in their 60s who are not taking HRT — on average, over a 5-year period, 11 in 1000 would be expected to have a stroke.

For women in their 60s who are taking HRT, the figure would be 15 in 1000.

If you get:

unexplained migraine-type headaches, with or without disturbed vision See a doctor as soon as possible and do not take any more HRT until your doctor says you can. These headaches may be an early warning sign of a stroke.

Blood clots

HRT may increase the risk of blood clots in the veins (also called deep vein thrombosis, or DVT), especially during the first year of taking it.

These blood clots are not always serious, but if one travels to the lungs, it can cause chest pain, breathlessness, collapse or even death. This condition is called pulmonary embolism, or PE.

DVT and PE are examples of a condition called venous thromboembolism, or VTE.

You are more likely to get a blood clot:

if you are seriously overweight if you have had a blood clot before if any of your close family have had blood clots if you have had one or more miscarriages if you have any blood clotting problem that needs treatment with a medicine such as warfarin if you’re off your feet for a long time because of major surgery, injury or illness if you have a rare condition called SLE.

If any of these things apply to you, talk to your doctor to see if you should take HRT.

Compare

Looking at women in their 50s who are not taking HRT — on average, over a 5-year period, 3 in 1000 would be expected to get a blood clot.

For women in their 50s who are taking HRT, the figure would be 7 in 1000.

Looking at women in their 60s who are not taking HRT — on average, over a 5-year period, 8 in 1000 would be expected to get a blood clot.

For women in their 60s who are taking HRT, the figure would be 17 in 1000.

If you get:

painful swelling in your leg sudden chest pain difficulty breathing. See a doctor as soon as possible and do not take any more HRT until your doctor says you can. These may be signs of a blood clot.

If you’re going to have an operation, make sure your doctor knows about it. You may need to stop taking HRT about 4 to 6 weeks before the operation, to reduce the risk of a blood clot. Your doctor will tell you when you can start taking HRT again.

Effects on your risk of developing cancer

Breast cancer

Women who have breast cancer, or have had breast cancer in the past, should not take HRT.

Taking HRT slightly increases the risk of breast cancer; so does having a later menopause. The risk for a post-menopausal woman taking oestrogen-only HRT for 5 years is about the same as for a woman of the same age who is still having periods over that time and not taking HRT. The risk for a woman who is taking oestrogen plus progestogen HRT is higher than for oestrogen-only HRT (but oestrogen plus progestogen HRT is beneficial for the lining of the womb (endometrium), see “Endometrial cancer” below).

For all kinds of HRT, the extra risk of breast cancer goes up the longer you take it, but returns to normal within about 5 years after stopping.

Your risk of breast cancer is also higher:

if you have a close relative (mother, sister or grandmother) who has had breast cancer if you are seriously overweight.

Compare

Looking at women aged 50 who are not taking HRT — on average, 32 in 1000 will be diagnosed with breast cancer by the time they reach the age of 65.

For women who start taking oestrogen-only HRT at age 50 and take it for 5 years, the figure will be between 33 and 34 in 1000 (ie an extra 1 – 2 cases).

If they take oestrogen-only HRT for 10 years, the figure will be 37 in 1000 (ie an extra 5 cases).

For women who start taking oestrogen plus progestogen HRT at age 50 and take it for 5 years the figure will be 38 in 1000 (ie an extra 6 cases)

If they take oestrogen plus progestogen HRT for 10 years, the figure will be 51 in 1000 (ie an extra 19 cases).

If you notice any changes in your breast, such as:

dimpling of the skin changes in the nipple any lumps you can see or feel Make an appointment to see your doctor as soon as possible.

Endometrial cancer (cancer of the lining of the womb)

Taking oestrogen-only HRT for a long time can increase the risk of cancer of the lining of the womb (the endometrium). Taking a progestogen as well as the oestrogen helps to lower the extra risk.

If you still have your womb, your doctor may prescribe a progestogen as well as oestrogen. If so, these may be prescribed separately, or as a combined HRT product.

If you have had your womb removed (a hysterectomy), your doctor will discuss with you whether you can safely take oestrogen without a progestogen.

If you’ve had your womb removed because of endometriosis, any endometrium left in your body may be at risk. So your doctor may prescribe HRT that includes a progestogen as well as an oestrogen.

Your product, Progynova TS 50 contains only oestrogen.

Compare

Looking at women who still have a uterus and who are not taking HRT – on average 5 in 1000 will be diagnosed with endometrial cancer between the ages of 50 and 65.

For women who take oestrogen-only HRT the number will be between 10 and 60 in 1000 depending on the dose and for how long it is taken.

The addition of a progestogen to oestrogen-only HRT substantially reduces the risk of endometrial cancer.

If you get breakthrough bleeding or spotting, it’s usually nothing to worry about, especially during the first few months of taking HRT.

But if the bleeding or spotting:

carries on for more than the first few months starts after you’ve been on HRT for a while carries on even after you’ve stopped taking HRT Make an appointment to see your doctor. It could be a sign that your endometrium has become thicker.

Ovarian cancer

Ovarian cancer (cancer of the ovaries) is very rare, but it is serious. It can be difficult to diagnose, because there are often no obvious signs of the disease.

Some studies have indicated that taking oestrogen-only HRT for more than 5 years may increase the risk of ovarian cancer. It is not yet known whether other kinds of HRT increase the risk in the same way.

Other important information

The use of hormone replacement therapy may affect the results of certain laboratory tests. Always tell your doctor or the laboratory staff that you are using hormone replacement therapy.

Brown patches on your face and body (chloasma) may occasionally occur, especially if you experienced this during a previous pregnancy. You can reduce this by not staying in the sun too long and by not using sunbeds or sunlamps.

HRT will not prevent memory loss. A study with one type of HRT (containing conjugated oestrogen plus the progestogen MPA) showed that women who started using this HRT after the age of 65 had a small increase in their risk of developing dementia. It is not known if this applies to other types of HRT or to younger women.

Progynova TS 50 is not a contraceptive. If there is any possibility that you may become pregnant ask your doctor for contraceptive advice. It is important that you use a reliable form of non-hormonal contraception such as a condom or cap plus spermicide. Oral contraceptives should not be used.

What to do if you are taking other medicines at the same time as Progynova TS 50

Some medicines may stop Progynova TS 50 from working properly and other medicines will be affected by Progynova TS 50.

Tell your doctor if you have to take any other medicines regularly, especially: medicines used to treat epilepsy or other illnesses, such as phenobarbitol, phenytoin, carbamazepine medicines used to treat certain infections, such as rifampicin, rifabutin, nevirapine, efavirenz medicines used to treat HIV infections, such as ritonavir, nelfinavir the herbal remedy commonly known as St John’s wort (Hypericum perforatum).

If in doubt about any medicines you are taking, ask your doctor or pharmacist.

How to use Progynova TS 50

If you are not currently using hormone treatment, or you use a type that does not cause a regular monthly bleed, you can start to use Progynova TS 50 immediately.

If you are changing from another type of hormone replacement therapy that causes a monthly bleed, you may be told to start Progynova TS 50 the day after stopping your treatment or when your doctor has told you to.

If you are changing from a 3-week on, 1-week off, type of hormone replacement therapy you may be told to start Progynova TS 50 the day after the treatment-free period (1-week off).

If you have not had a hysterectomy, your doctor may have prescribed a progestogen separately in addition to Progynova TS 50. Follow your doctor’s instructions.

To apply Progynova TS 50: the patch should be applied to a clean, dry area of skin preferably on the stomach or buttocks. Progynova TS 50 must not be applied on or near the breasts. The area chosen should not be oily, damaged or irritated, and the waistline should be avoided since tight clothing may rub the patch off.

Take the patch out of its packaging. Remove the protective liner. The patch should then immediately be pressed firmly in place with the palm of the hand for about 10 seconds. Make sure there is good contact with the skin; especially around the edges.

The patch should be left in place for 7 days, then removed and replaced with a new patch which should be applied to a different area.

Although the patches should usually be applied continuously, your doctor may tell you to apply the patches on a cyclical basis. In this case, a patch should be applied weekly for 3 weeks followed by a 7 day interval without a patch application before the next course.

You will be able to bath or shower as normal while wearing a patch. However, the patch may fall off in very hot water or in a sauna.

After use, Progynova TS 50 patches still contain large amounts of the active ingredient estradiol. Take care when throwing away used and unused patches. Fold patches in half with the sticky sides together and throw away with your dustbin waste. Patches must not be flushed down the toilet.

What to do if a patch falls off

If a patch falls off before 7 days are up, it may be reapplied. If necessary a new patch may be used if it is not possible to reattach the old patch properly. If a new patch is used it should be kept on for the remainder of the 7 days and then changed on your usual day for applying a new patch.

What to do if you forget a patch

If you forget to put a patch on, put it on as soon as you remember and keep it on for 7 days before replacing with a new patch. If you are several days late in changing your patch, you may get some light vaginal bleeding (spotting) at unexpected times.

What to do if you use too many patches

If you use too many patches, it is unlikely to cause you any serious problems but you may feel sick, actually be sick or have some vaginal bleeding. If you are worried, talk to your doctor or pharmacist who can tell you what, if anything, you need to do.

Possible side effects

The most frequently reported reactions during the first few months of treatment are breast tenderness or enlargement or vaginal bleeding at unexpected times (breakthrough bleeding or spotting). These are usually temporary and normally disappear with continued treatment.

Below we list other possible side effects by how likely they are to occur:

Common

Between 1 and 10 in every 100 people are likely to get these:

Pain; excessive gas or belching; feeling sick; swelling caused by build up of fluid in arms, legs or other parts of the body; weight gain; depression; dizziness; nervousness; feeling sluggish; headache; increased sweating; hot flushes; itchy rash which may be around the patch; changes to menstrual bleeding; vaginal discharge; vaginal and genital problems.

Uncommon

Less than 1 in every 100 people are likely to get these:

Feeling weak, tired or generally unwell; abnormal laboratory tests; fever, flu-like symptoms; migraine; fast or irregular heartbeats (palpitations); inflamed and itchy veins, usually in the legs (phlebitis); increased blood pressure; increased appetite; constipation; diarrhoea; back passage problems; high level of blood fats (cholesterol); joint problems and muscle cramps; difficulty breathing; runny nose; trouble sleeping; mood changes; problems concentrating; pins and needles; changes to sex drive; shaking or tremor; loss of hair, excessive hair growth; lumpy, enlarged or tender breasts; skin rashes; acne; dry skin or small skin swelling; nail problems; problems with frequency and control of urine; discoloured urine; blood in urine; changes to the lining of the womb which may cause heavier vaginal bleeding; bladder infections (cystitis); dry eyes; eyesight problems.

Rare

Less than 1 in every 1000 people are likely to get these::

Stomach pain or bloating; yellowing of the skin or eyes (jaundice); inflammatory skin rashes; breast pain; fibroids.

Other side effects reported with HRT include:

The risk of breast cancer increases with the number of years of using HRT. Cancer of the lining of the womb (endometrial cancer) has also been reported. See “Effects on your risk of developing cancer” for more information.

Blood clots, heart attacks and stroke (see “Effects on your heart or circulation” for more information); dementia , increased skin pigment especially on the face (chloasma) (see “Other important information” for more information); some rare skin problems and gall bladder disease.

Worsening of hereditary angioedema with swelling of the skin and/or mucous membranes such as swollen face, lips, tongue and/or throat and/or difficulty swallowing or hives together with difficulty breathing.

Tell your doctor if you have any of the symptoms listed above, or indeed any other new symptoms during treatment. Also tell your doctor if you have any of the symptoms listed under “Reasons for stopping Progynova TS 50”. Reasons for stopping Progynova TS 50 Stop treatment (remove the patch) at once and talk to your doctor immediately if you have any of the following: your very first attack of migraine (typically a throbbing headache and nausea preceded by visual disturbances); if you get a blood clot – see the section “Blood clots” on for warning signs of a blood clot. you have difficulty breathing or have worsening of hereditary angioedema. Stop treatment (remove the patch) at once and talk to your doctor as soon as you can if you have any of the following: if you become pregnant if you develop jaundice (get yellowing of the skin or eyes) if you develop any of the conditions listed under “Reasons for not using Progynova TS 50” . Your doctor may decide that you should stop using Progynova TS 50 if: your liver function tests become abnormal there is a significant rise in your blood pressure you are off your feet for a long time because of major surgery, injury or illness. See also the section “Blood clots” on, especially if you are going to have an operation. How to store Progynova TS 50

Store your patches in the original packaging in order to protect from moisture.Store below 30?C.

Keep your patches in a safe place where children cannot see or reach them.

Do not use the patches after the expiry date that is shown on the box.

Date of last revision of this booklet: May 2008

Progynova is a registered trademark of Bayer Schering Pharma AG (formerly Schering AG).


read more


Fluorouracil Topical Solution



Fluorouracil Topical SolutionS

Rx only

FOR TOPICAL USE ONLY - NOT FOR OPHTHALMIC, ORAL, OR INTRAVAGINAL USE.

DESCRIPTION

Fluorouracil Solutions are topical preparations containing the fluorinated pyrimidine 5-fluorouracil, an antineoplastic antimetabolite.

Fluorouracil Solution consists of 2% or 5% fluorouracil on a weight/weight basis, compounded with propylene glycol, tris (hydroxymethyl) aminomethane, hydroxypropyl cellulose, parabens (methyl and propyl), disodium edentate and purified water.

Chemically, fluorouracil is 5-fluoro-2,4(1H,3H)-pyrimidinedione. It is a white to practically white, crystalline powder which is sparingly soluble in water and slightly soluble in alcohol. One gram of fluorouracil is soluble in 100 mL of propylene glycol. The molecular weight of 5-fluorouracil is 130.08 and the structural formula is:

CLINICAL PHARMACOLOGY

There is evidence that the metabolism of fluorouracil in the anabolic pathway blocks the methylation reaction of deoxyuridylic acid to thymidylic acid. In this manner fluorouracil interferes with the synthesis of deoxyribonucleic acid (DNA) and to a lesser extent inhibits the formation of ribonucleic acid (RNA). Since DNA and RNA are essential for cell division and growth, the effect of fluorouracil may be to create a thymine deficiency which provokes unbalanced growth and death of the cell. The effects of DNA and RNA deprivation are most marked on those cells which grow more rapidly and take up fluorouracil at a more rapid rate. The catabolic metabolism of fluorouracil results in degradation products (e.g., CO2, urea, ?-fluoro-?-alanine) which are inactive.

Systemic absorption studies of topically applied fluorouracil have been performed on patients with actinic keratoses using tracer amounts of 14C labeled fluorouracil added to a 5% preparation. All patients had been receiving non labeled fluorouracil until the peak of the inflammatory reaction occurred (2 to 3 weeks), ensuring that the time of maximum absorption was used for measurement. One gram of labeled preparation was applied to the entire face and neck and left in place for 12 hours. Urine samples were collected. At the end of 3 days, the total recovery ranged between 0.48% and 0.94% with an average of 0.76%, indicating that approximately 5.98% of the topical dose was absorbed systemically. If applied twice daily, this would indicate systemic absorption of topical fluorouracil to be in the range of 5 to 6 mg per daily dose of 100 mg. In an additional study, negligible amounts of labeled material were found in plasma, urine and expired CO2 after 3 days of treatment with topically applied 14C-labeled fluorouracil.

INDICATIONS & USAGE

Fluorouracil is recommended for the topical treatment of multiple actinic or solar keratoses. In the 5% strength it is also useful in the treatment of superficial basal cell carcinomas when conventional methods are impractical, such as with multiple lesions or difficult treatment sites. Safety and efficacy in other indications have not been established.

The diagnosis should be established prior to treatment, since this method has not been proven effective in other types of basal cell carcinomas. With isolated, easily accessible basal cell carcinomas, surgery is preferred since success with such lesions is almost 100%. The success rate with Fluorouracil Solution is approximately 93%, based on 113 lesions in 54 patients. Twenty-five lesions treated with the solution produced 1 failure.

CONTRAINDICATIONS

Fluorouracil may cause fetal harm when administered to a pregnant woman.

There are no adequate and well-controlled studies in pregnant women with either the topical or the parenteral forms of fluorouracil. One birth defect (cleft lip and palate) has been reported in the newborn of a patient using Fluorouracil as recommended. One birth defect (ventricular septal defect) and cases of miscarriage have been reported when Fluorouracil was applied to mucous membrane areas. Multiple birth defects have been reported in a fetus of a patient treated with intravenous fluorouracil.

Animal reproduction studies have not been conducted with Fluorouracil. Fluorouracil administered parenterally has been shown to be teratogenic in mice, rats, and hamsters when given at doses equivalent to the usual human intravenous dose; however, the amount of fluorouracil absorbed systemically after topical administration to actinic keratoses is minimal (see CLINICAL PHARMACOLOGY). Fluorouracil exhibited maximum teratogenicity when given to mice as single intraperitoneal injections of 10 to 40 mg/kg on Day 10 or 12 of gestation. Similarly, intraperitoneal doses of 12 to 37 mg/kg given to rats between Days 9 and 12 of gestation and intramuscular doses of 3 to 9 mg/kg given to hamsters between Days 8 and 11 of gestation were teratogenic and/or embryotoxic (i.e., resulted in increased resorptions or embryolethality). In monkeys, divided doses of 40 mg/kg given between Days 20 and 24 of gestation were not teratogenic. Doses higher than 40 mg/kg resulted in abortion.

Fluorouracil should not be used in patients with dihydropyrimidine dehydrogenase (DPD) enzyme deficiency. A large percentage of fluorouracil is catabolized by the DPD enzyme. DPD enzyme deficiency can result in shunting of fluorouracil to the anabolic pathway, leading to cytotoxic activity and potential toxicities.

Fluorouracil is contraindicated in women who are or may become pregnant

during therapy. If this drug is used during pregnancy, or if the patient becomes pregnant while using this drug, the patient should be apprised of the potential hazard to the fetus.

Fluorouracil is also contraindicated in patients with known hypersensitivity to any of its components.

WARNINGS

Application to mucous membranes should be avoided due to the possibility of local inflammation and ulceration. Additionally, cases of miscarriage and a birth defect (ventricular septal defect) have been reported when Fluorouracil was applied to mucous membrane areas during pregnancy.

Occlusion of the skin with resultant hydration has been shown to increase percutaneous penetration of several topical preparations. If any occlusive dressing is used in treatment of basal cell carcinoma, there may be an increase in the severity of inflammatory reactions in the adjacent normal skin. A porous gauze dressing may be applied for cosmetic reasons without increase in reaction.

Exposure to ultraviolet rays should be minimized during and immediately following treatment with Fluorouracil because the intensity of the reaction may be increased.

Patients should discontinue therapy with Fluorouracil if symptoms of DPD enzyme deficiency develop (see CONTRAINDICATIONS section).

Rarely, life-threatening toxicities such as stomatitis, diarrhea, neutropenia, and neurotoxicity have been reported with intravenous administration of fluorouracil in patients with DPD enzyme deficiency. One case of life threatening systemic toxicity has been reported with the topical use of Fluorouracil in a patient with DPD enzyme deficiency. Symptoms included severe abdominal pain, bloody diarrhea, vomiting, fever, and chills. Physical examination revealed stomatitis, erythematous skin rash, neutropenia, thrombocytopenia, inflammation of the esophagus, stomach, and small bowel. Although this case was observed with 5% fluorouracil cream, it is unknown whether patients with profound DPD enzyme deficiency would develop systemic toxicity with lower concentrations of topically applied fluorouracil.

PRECAUTIONS

General: There is a possibility of increased absorption through ulcerated or inflamed skin.

Information for Patients: Patients should be forewarned that the reaction in the treated areas may be unsightly during therapy and, usually, for several weeks following cessation of therapy. Patients should be instructed to avoid exposure to ultraviolet rays during and immediately following treatment with Fluorouracil because the intensity of the reaction may be increased. If Fluorouracil is applied with the fingers, the hands should be washed immediately afterward. Fluorouracil should not be applied on the eyelids or directly into the eyes, nose or mouth because irritation may occur.

Laboratory Tests: Solar keratoses which do not respond should be biopsied to confirm the diagnosis. Follow-up biopsies should be performed as indicated in the management of superficial basal cell carcinoma.

Carcinogenesis, Mutagenesis, Impairment of Fertility: Adequate long term studies in animals to evaluate carcinogenic potential have not been conducted with fluorouracil. Studies with the active ingredient of Fluorouracil, 5-fluorouracil, have shown positive effects in in vitro tests for mutagenicity and on impairment of fertility.

5-Fluorouracil was positive in three in vitro cell neoplastic transformation assays. In the C3H/10T1? 2 clone 8 mouse embryo cell system, the resulting morphologically transformed cells formed tumors when inoculated into immunosuppressed syngeneic mice.

While no evidence for mutagenic activity was observed in the Ames test (3 studies), fluorouracil has been shown to be mutagenic in the survival count rec-assay with Bacillus subtilis and in the Drosophilia wing-hair spot test. Fluorouracil produced petite mutations in Saccharomyces cerevisiae and was positive in the micronucleus test (bone marrow cells of male mice).

Fluorouracil was clastogenic in vitro (i.e., chromatid gaps, breaks and exchanges) in Chinese hamster fibroblasts at concentrations of 1.0 and 2.0 mg/mL and has been shown to increase sister chromatid exchange in vitro in human lymphocytes. In addition, 5-fluorouracil has been reported to produce an increase in numerical and structural chromosome aberrations in peripheral lymphocytes of patients treated with this product.

Doses of 125 to 250 mg/kg, administered intraperitoneally, have been shown to induce chromosomal aberrations and changes in chromosome organization of spermatogonia in rats. Spermatogonial differentiation was also inhibited by fluorouracil, resulting in transient infertility. However, in studies with a strain of mouse which is sensitive to the induction of sperm head abnormalities after exposure to a range of chemical mutagens and carcinogens, fluorouracil was inactive at oral doses of 5 to 80 mg/kg/day. In female rats, fluorouracil administered intraperitoneally at doses of 25 and 50 mg/kg during the preovulatory phase of oogenesis significantly reduced the incidence of fertile matings, delayed the development of preimplantation and postimplantation embryos, increased the incidence of preimplantation lethality and induced chromosomal anomalies in these embryos. Single dose intravenous and intraperitoneal injections of 5-fluorouracil have been reported to kill differentiated spermatogonia and spermatocytes (at 500 mg/kg) and to produce abnormalities in spermatids (at 50 mg/kg) in mice.

Pregnancy:

Teratogenic Effects:

Pregnancy Category X: See CONTRAINDICATIONS section.

Nursing Mothers: It is not known whether Fluorouracil is excreted in human milk. Because there is some systemic absorption of fluorouracil after topical administration (see CLINICAL PHARMACOLOGY), because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue use of the drug, taking into account the importance of the drug to the mother.

Pediatric Use: Safety and effectiveness in children have not been established.

ADVERSE REACTIONS

The most frequent adverse reactions to Fluorouracil occur locally and are often related to an extension of the pharmacological activity of the drug. These include burning, crusting, allergic contact dermatitis, erosions, erythema, hyperpigmentation, irritation, pain, photosensitivity, pruritus, scarring, rash, soreness and ulceration. Ulcerations, other local reactions, cases of miscarriage and a birth defect (ventricular septal defect) have been reported when Fluorouracil was applied to mucous membrane areas. Leukocytosis is the most frequent hematological side effect.

Although a causal relationship is remote, other adverse reactions which have been reported infrequently are:

Central Nervous System: Emotional upset, insomnia, irritability.

Gastrointestinal: Medicinal taste, stomatitis.

Hematological: Eosinophilia, thrombocytopenia, toxic granulation.

Integumentary: Alopecia, blistering, bullous pemphigoid, discomfort, ichthyosis, scaling, suppuration, swelling, telangiectasia, tenderness, urticaria, skin rash.

Special Senses: Conjunctival reaction, corneal reaction, lacrimation, nasal irritation.

Miscellaneous: Herpes simplex.

OVERDOSAGE

There have been no reports of overdosage with Fluorouracil.

Studies with a 5% topical solution yielded an oral LD50 of 214 mg/kg in rats and 28.5 mg/kg in dogs, corresponding to 10.7 and 1.43 mg/kg of fluorouracil, respectively.

DOSAGE & ADMINISTRATION

When Fluorouracil is applied to a lesion, a response occurs with the following sequence: erythema, usually followed by vesiculation, desquamation, erosion and reepithelialization.

Fluorouracil should be applied preferably with a nonmetal applicator or suitable glove. If Fluorouracil is applied with the fingers, the hands should be washed immediately afterward.

Actinic or Solar Keratosis: Apply solution twice daily in an amount sufficient to cover the lesions. Medication should be continued until the inflammatory response reaches the erosion stage, at which time use of the drug should be terminated. The usual duration of therapy is from 2 to 4 weeks. Complete healing of the lesions may not be evident for 1 to 2 months following cessation of Fluorouracil therapy.

Superficial Basal Cell Carcinomas: Only the 5% strength is recommended. Apply solution twice daily in an amount sufficient to cover the lesions. Treatment should be continued for at least 3 to 6 weeks. Therapy may be required for as long as 10 to 12 weeks before the lesions are obliterated. As in any neoplastic condition, the patient should be followed for a reasonable period of time to determine if a cure has been obtained.

HOW SUPPLIED

Fluorouracil Solution is available in 10-mL drop dispensers containing either 2% (NDC 43547-259-01) or 5% (NDC 43547-258-01) fluorouracil on a weight/weight basis compounded with propylene glycol, tris (hydroxymethyl) aminomethane, hydroxypropyl cellulose, parabens (methyl and propyl), disodium edentate and purified water.

Store at 25°C (77°F); excursions permitted to 15°C-30°C (59°F-86°F).

Manufactured by:
Legacy Pharmaceuticals Puerto Rico, LLC
Humacao, Puerto Rico 00791

Distributed by:
Solco Healthcare US, LLC
Humacao, Puerto Rico 00791

Rev. April, 2010

Code: 02-3608-EX-02

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

Fluorouracil 2% Topical Solution
NDC 43547-259-01

Bottle Label

Carton Label

Fluorouracil 2% Topical Solution
NDC 43547-259-01

Packer Label

Fluorouracil 5% Topical Solution
NDC 43547-258-01

Bottle Label

Carton Label


FLUOROURACIL 
fluorouracil  solution Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 43547-259 Route of Administration TOPICAL DEA Schedule      Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength FLUOROURACIL (FLUOROURACIL) FLUOROURACIL 20 mg  in 1 mL Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains          Packaging # NDC Package Description Multilevel Packaging 1 43547-259-01 10 mL In 1 BOTTLE, PLASTIC None
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA016831 06/01/2010
FLUOROURACIL 
fluorouracil  solution Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 43547-258 Route of Administration TOPICAL DEA Schedule      Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength FLUOROURACIL (FLUOROURACIL) FLUOROURACIL 50 mg  in 1 mL Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains          Packaging # NDC Package Description Multilevel Packaging 1 43547-258-01 10 mL In 1 BOTTLE, PLASTIC None
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA016831 06/01/2010
Labeler - Solco Healthcare US LLC (828343017) Registrant - Solco Healthcare US LLC (828343017) Establishment Name Address ID/FEI Operations Legacy Pharmaceuticals Puerto Rico LLC 026611520 ANALYSIS, API MANUFACTURE, LABEL Revised: 05/2010Solco Healthcare US LLC More Fluorouracil Topical Solution resources Fluorouracil Topical Solution Use in Pregnancy & Breastfeeding Fluorouracil Topical Solution Support Group 23 Reviews for Fluorouracil Topical - Add your own review/rating Compare Fluorouracil Topical Solution with other medications Actinic Keratosis Basal Cell Carcinoma Skin Cancer
read more


Apraclonidine



Dosage Form: ophthalmic solution
Apraclonidine Ophthalmic Solution, 0.5% as base DESCRIPTION

Apraclonidine Ophthalmic Solution contains Apraclonidine hydrochloride, an alpha adrenergic agonist, in a sterile isotonic solution for topical application to the eye. Apraclonidine hydrochloride is a white to off-white powder and is highly soluble in water. Its chemical name is 2-[(4-amino-2,6 dichlorophenyl) imino]imidazolidine monohydrochloride with an empirical formula of C9H11Cl3N4 and a molecular weight of 281.57. The chemical structure of Apraclonidine hydrochloride is:

Each mL of Apraclonidine Ophthalmic Solution contains: Active: Apraclonidine hydrochloride 5.75 mg equivalent to Apraclonidine base 5 mg; Preservative: benzalkonium chloride 0.01%. Inactives: sodium chloride, sodium acetate, sodium hydroxide and/or hydrochloric acid (pH 4.4-7.8) and purified water.

CLINICAL PHARMACOLOGY

Apraclonidine hydrochloride is a relatively selective alpha-2-adrenergic agonist. When instilled in the eye, Apraclonidine Ophthalmic Solution, has the action of reducing elevated, as well as normal, intraocular pressure (IOP), whether or not accompanied by glaucoma. Ophthalmic Apraclonidine has minimal effect on cardiovascular parameters. Elevated IOP presents a major risk factor in glaucomatous field loss. The higher the level of IOP, the greater the likelihood of optic nerve damage and visual field loss. Apraclonidine Ophthalmic Solution has the action of reducing IOP. The onset of action of Apraclonidine can usually be noted within one hour, and maximum IOP reduction occurs about three hours after instillation. Aqueous fluorophotometry studies demonstrate that Apraclonidine's predominant mechanism of action is reduction of aqueous flow via stimulation of the alpha-adrenergic system.

Repeated dose-response and comparative studies (0.125% - 1.0% Apraclonidine) demonstrate that 0.5% Apraclonidine is at the top of the dose/response IOP reduction curve.

The clinical utility of Apraclonidine Ophthalmic Solution is most apparent for those glaucoma patients on maximally tolerated medical therapy. Patients on maximally tolerated medical therapy with uncontrolled IOP and scheduled to undergo laser trabeculoplasty or trabeculectomy surgery were enrolled into a double-masked, placebo-controlled, multi-center clinical trial to determine if Apraclonidine Ophthalmic Solution, 0.5% as base dosed three times daily (TID), could delay the need for surgery for up to three months.

All patients enrolled into this trial had advanced glaucoma and were undergoing maximally tolerated medical therapy, i.e., patients were using combinations of a topical beta blocker, sympathomimetics, parasympathomimetics and oral carbonic anhydrase inhibitors. Patients were considered to be treatment failures in this study if, in the opinion of the investigators, their IOP was uncontrolled by the masked study medication or there was evidence of further optic nerve damage or visual field loss, and surgery was indicated. Of 171 patients receiving masked medication, 84 were treated with Apraclonidine Ophthalmic Solution and 87 were treated with placebo (Apraclonidine vehicle). Apraclonidine treatment resulted in a significantly greater percentage of treatment successes compared to patients treated with placebo. In this placebo-controlled maximum therapy trial, 14.3% of patients treated with Apraclonidine Ophthalmic Solution were discontinued due to adverse events, primarily allergic-like reactions (12.9%).

The IOP lowering efficacy of Apraclonidine Ophthalmic Solution diminishes over time in some patients. This loss of effect, or tachyphylaxis, appears to be an individual occurrence with a variable time of onset and should be closely monitored.

An unpredictable decrease of IOP control in some patients and incidence of ocular allergic responses and systemic side effects may limit the utility of Apraclonidine Ophthalmic Solution. However, patients on maximally tolerated medical therapy may still benefit from the additional IOP reduction provided by the short-term use of Apraclonidine Ophthalmic Solution.

Topical use of Apraclonidine Ophthalmic Solution leads to systemic absorption. Studies of Apraclonidine Ophthalmic Solution dosed one drop three times a day in both eyes for 10 days in normal volunteers yielded mean peak and trough concentrations of 0.9 ng/mL and 0.5 ng/mL, respectively. The half-life of Apraclonidine Ophthalmic Solution, 0.5% as base was calculated to be 8 hours.

Apraclonidine Ophthalmic Solution, because of its alpha adrenergic activity, is a vasoconstrictor. Single dose ocular blood flow studies in monkeys, using the microsphere technique, demonstrated a reduced blood flow for the anterior segment; however, no reduction in blood flow was observed in the posterior segment of the eye after a topical dose of Apraclonidine Ophthalmic Solution. Ocular blood flow studies have not been conducted in humans.

INDICATIONS AND USAGE

Apraclonidine Ophthalmic Solution, 0.5% as base is indicated for short-term adjunctive therapy in patients on maximally tolerated medical therapy who require additional IOP reduction. Patients on maximally tolerated medical therapy who are treated with Apraclonidine Ophthalmic Solution to delay surgery should have frequent followup examinations and treatment should be discontinued if the intraocular pressure rises significantly.

The addition of Apraclonidine Ophthalmic Solution to patients already using two aqueous suppressing drugs (i.e., beta-blocker plus carbonic anhydrase inhibitor) as part of their maximally tolerated medical therapy may not provide additional benefit. This is because Apraclonidine Ophthalmic Solution is an aqueous suppressing drug and the addition of a third aqueous suppressant may not significantly reduce IOP.

The IOP lowering efficacy of Apraclonidine Ophthalmic Solution diminishes over time in some patients. This loss of effect, or tachyphylaxis, appears to be an individual occurrence with a variable time of onset and should be closely monitored. The benefit for most patients is less than one month.

CONTRAINDICATIONS

Apraclonidine Ophthalmic Solution is contraindicated in patients with hypersensitivity to Apraclonidine or any other component of this medication, as well as systemic clonidine. It is also contraindicated in patients receiving monoamine oxidase inhibitors (MAO inhibitors).

WARNINGS

Not for injection or oral ingestion. FOR TOPICAL OPHTHALMIC USE ONLY.

PRECAUTIONS General

Glaucoma patients on maximally tolerated medical therapy who are treated with Apraclonidine Ophthalmic Solution to delay surgery should have their visual fields monitored periodically.

Although the topical use of Apraclonidine Ophthalmic Solution has not been studied in renal failure patients, structurally related clonidine undergoes a significant increase in half-life in patients with severe renal impairment. Close monitoring of cardiovascular parameters in patients with impaired renal function is advised if they are candidates for topical Apraclonidine therapy. Close monitoring of cardiovascular parameters in patients with impaired liver function is also advised as the systemic dosage form of clonidine is partly metabolized in the liver.

While the topical administration of Apraclonidine Ophthalmic Solution had minimal effect on heart rate or blood pressure in clinical studies evaluating glaucoma patients, the preclinical pharmacology profile of this drug suggests that caution should be observed in treating patients with severe, uncontrolled cardiovascular disease, including hypertension.

Apraclonidine Ophthalmic Solution should be used with caution in patients with coronary insufficiency, recent myocardial infarction, cerebrovascular disease, chronic renal failure, Raynaud's disease, or thromboangiitis obliterans. Caution and monitoring of depressed patients are advised since Apraclonidine has been infrequently associated with depression.

Apraclonidine can cause dizziness and somnolence. Patients who engage in hazardous activities requiring mental alertness should be warned of the potential for a decrease in mental alertness while using Apraclonidine. Topical ocular administration of two drops of 0.5, 1.0 and 1.5% Apraclonidine ophthalmic solution to New Zealand albino rabbits three times daily for one month resulted in sporadic and transient instances of minimal corneal edema in the 1.5% group only; no histopathological changes were noted in those eyes. Use of Apraclonidine Ophthalmic Solution can lead to an allergic-like reaction characterized wholly or in part by the symptoms of hyperemia, pruritus, discomfort, tearing, foreign body sensation, and edema of the lids and conjunctiva. If ocular allergic-like symptoms occur, Apraclonidine Ophthalmic Solution therapy should be discontinued.

Patient Information

Do not touch dropper tip to any surface as this may contaminate the contents.

Drug Interactions

Apraclonidine should not be used in patients receiving MAO inhibitors. (See CONTRAINDICATIONS). Although no specific drug interactions with topical glaucoma drugs or systemic medications were identified in clinical studies of Apraclonidine Ophthalmic Solution, the possibility of an additive or potentiating effect with CNS depressants (alcohol, barbiturates, opiates, sedatives, anesthetics) should be considered. Tricyclic antidepressants have been reported to blunt the hypotensive effect of systemic clonidine. It is not known whether the concurrent use of these agents with Apraclonidine can lead to a reduction in IOP lowering effect. No data on the level of circulating catecholamines after Apraclonidine withdrawal are available. Caution, however, is advised in patients taking tricyclic antidepressants which can affect the metabolism and uptake of circulating amines.

An additive hypotensive effect has been reported with the combination of systemic clonidine and neuroleptic therapy. Systemic clonidine may inhibit the production of catecholamines in response to insulin-induced hypoglycemia and mask the signs and symptoms of hypoglycemia.

Since Apraclonidine may reduce pulse and blood pressure, caution in using drugs such as beta-blockers (ophthalmic and systemic), antihypertensives, and cardiac glycosides is advised. Patients using cardiovascular drugs concurrently with Apraclonidine Ophthalmic Solution should have pulse and blood pressures frequently monitored. Caution should be exercised with simultaneous use of clonidine and other similar pharmacologic agents.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No significant change in tumor incidence or type was observed following two years of oral administration of Apraclonidine HCl to rats and mice at dosages of 1.0 and 0.6 mg/kg, up to 20 and 12 times, respectively, the maximum dose recommended for human topical ocular use.

Apraclonidine HCl was not mutagenic in a series of in vitro mutagenicity tests, including the Ames test, a mouse lymphoma forward mutation assay, a chromosome aberration assay in cultured Chinese hamster ovary (CHO) cells, a sister chromatid exchange assay in CHO cells, and a cell transformation assay.

An in vivo mouse micronucleus assay conducted with Apraclonidine HCl also provided no evidence of mutagenicity.

Reproduction and fertility studies in rats showed no adverse effect on male or female fertility at a dose of 0.5 mg/kg (5 to 10 times the maximum recommended human dose).

Pregnancy

Pregnancy Category C: Apraclonidine HCl has been shown to have an embryocidal effect in rabbits when given in an oral dose of 3.0 mg/kg (60 times the maximum recommended human dose). Dose related maternal toxicity was observed in pregnant rats at 0.3 mg/kg (6 times the maximum recommended human dose). There are no adequate and well controlled studies in pregnant women. Apraclonidine Ophthalmic Solution should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Apraclonidine Ophthalmic Solution is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

No overall differences in safety or effectiveness have been observed between elderly and younger patients.

ADVERSE REACTIONS

In clinical studies the overall discontinuation rate related to Apraclonidine Ophthalmic Solution was 15%. The most commonly reported events leading to discontinuation included (in decreasing order of frequency) hyperemia, pruritus, tearing, discomfort, lid edema, dry mouth, and foreign body sensation.

The following adverse reactions (incidences) were reported in clinical studies of Apraclonidine Ophthalmic Solution as being possibly, probably, or definitely related to therapy:

Ocular

The following adverse reactions were reported in 5 to 15% of the patients: discomfort, hyperemia, and puritus.

The following adverse reactions were reported in 1 to 5% of the patients: blanching, blurred vision, conjunctivitis, discharge, dry eye, foreign body sensation, lid edema, and tearing. The following adverse reactions were reported in less than 1% of the patients: abnormal vision, blepharitis, blepharoconjunctivitis, conjunctival edema, conjunctival follicles, corneal erosion, corneal infiltrate, corneal staining, edema, irritation, keratitis, keratopathy, lid disorder, lid erythema, lid margin crusting, lid retraction, lid scales, pain, photophobia.

Nonocular

Dry mouth occurred in approximately 10% of the patients.

The following adverse reactions were reported in less than 3% of the patients: abnormal coordination, asthenia, arrhythmia, asthma, chest pain, constipation, contact dermatitis, depression, dermatitis, dizziness, dry nose, dyspnea, facial edema, headache, insomnia, malaise, myalgia, nausea, nervousness, paresthesia, parosmia, peripheral edema, pharyngitis, rhinitis, somnolence, and taste perversion.

Clinical practice: The following events have been identified during post-marketing use of Apraclonidine Ophthalmic Solution in clinical practice. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. The events, which have been chosen for inclusion due to either their seriousness, frequency of reporting, possible causal connection to Apraclonidine Ophthalmic Solution, or a combination of these factors, include: bradycardia.

OVERDOSAGE

Ingestion of Apraclonidine Ophthalmic Solution, 0.5% as base has been reported to cause bradycardia, drowsiness, and hypothermia.

Accidental or intentional ingestion of oral clonidine has been reported to cause apnea, arrhythmias, asthenia, bradycardia, conduction defects, diminished or absent reflexes, dryness of the mouth, hypotension, hypothermia, hypoventilation, irritability, lethargy, miosis, pallor, respiratory depression, sedation or coma, seizure, somnolence, transient hypertension, and vomiting.

Treatment of an oral overdose includes supportive and symptomatic therapy; a patent airway should be maintained. Hemodialysis is of limited value since a maximum of 5% of circulating drug is removed.

DOSAGE AND ADMINISTRATION

One to two drops of Apraclonidine Ophthalmic Solution, 0.5% as base should be instilled in the affected eye(s) three times daily. Since Apraclonidine Ophthalmic Solution will be used with other ocular glaucoma therapies, an approximate 5 minute interval between instillation of each medication should be practiced to prevent washout of the previous dose.

NOT FOR INJECTION INTO THE EYE. NOT FOR ORAL INGESTION.

HOW SUPPLIED

Apraclonidine Ophthalmic Solution, 0.5% as base in a sterile, isotonic, aqueous solution containing Apraclonidine hydrochloride.

Supplied in plastic ophthalmic DROP-TAINER®* dispenser as follows:

5 mL NDC 61314-665-05

10 mL NDC 61314-665-10

Storage: Store between 2 - 27°C (36 - 80°F). Protect from freezing and light.

Rx Only

*DROP-TAINER® is a registered trademark of Alcon Research, Ltd.

Dist. by:

FALCON Pharmaceuticals, Ltd.

Fort Worth, Texas 76134 USA

Mfd. by:

ALCON LABORATORIES, INC.

Fort Worth, Texas 76134 USA

Printed in USA

©2009 Falcon Pharmaceuticals, Ltd.

9004584-0309

PRINCIPLE DISPLAY PANEL

NDC 61314-665-05         Rx Only

FALCON® PHARMACEUTICALS

Apraclonidine Ophthalmic Solution

0.5% as base

FOR TOPICAL OPHTHALMIC USE ONLY

0.5%

5mL            STERILE

AFFILIATE OF ALCON LABORATORIES, INC.

QUALITY RX


Apraclonidine 
Apraclonidine  solution Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 61314-665 Route of Administration OPHTHALMIC DEA Schedule      Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Apraclonidine HYDROCHLORIDE (Apraclonidine) Apraclonidine HYDROCHLORIDE 5.75 mg  in 1 mL Inactive Ingredients Ingredient Name Strength BENZALKONIUM CHLORIDE   SODIUM CHLORIDE   SODIUM ACETATE   SODIUM HYDROXIDE   HYDROCHLORIC ACID   WATER   Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains          Packaging # NDC Package Description Multilevel Packaging 1 61314-665-05 5 mL In 1 BOTTLE None 2 61314-665-10 10 mL In 1 BOTTLE None
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA authorized generic NDA020258 07/19/2009
Labeler - Falcon Pharmaceuticals, Ltd. (874345820) Registrant - Alcon Laboratories, Inc. (008018525) Establishment Name Address ID/FEI Operations Alcon Laboratories, Inc. 008018525 MANUFACTURE Revised: 08/2011Falcon Pharmaceuticals, Ltd. More Apraclonidine resources Apraclonidine Side Effects (in more detail) Apraclonidine Dosage Apraclonidine Use in Pregnancy & Breastfeeding Apraclonidine Drug Interactions Apraclonidine Support Group 0 Reviews for Apraclonidine - Add your own review/rating Compare Apraclonidine with other medications Glaucoma Postoperative Increased Intraocular Pressure
read more


Estraderm MX


ESTRADERM MX 25, 50, 75 and 100

(estradiol)

These patches will usually be referred to as Estraderm MX in this leaflet

What you need to know about Estraderm MX

Your doctor has decided that you need this medicine to help treat your condition.

Please read this leaflet carefully before you start to use the patches. It contains important information. Keep the leaflet in a safe place because you may want to read it again.

If you have any other questions, or if there is something you don’t understand, please ask your doctor or pharmacist.

This medicine has been prescribed for you. Never give it to someone else. It may not be the right medicine for them even if their symptoms seem to be the same as yours.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

In this leaflet: 1. What Estraderm MX patches are, and what they are used for 2. Things to consider before you start to use Estraderm MX patches 3. How to use Estraderm MX patches 4. Possible side effects 5. How to store the patches 6. Further information What Estraderm MX patches are and what they are used for

Estraderm MX is a patch which you stick on your skin. The patch contains a supply of estradiol which is released from the patch and absorbed through the skin into your blood stream. This is called a transdermal patch.

The active ingredient in the patches is estradiol. This is one of a group of hormones called estrogens which are the natural female sex hormone produced in large amounts by the ovaries before the menopause. After the menopause the ovaries produce less estrogen.

Estraderm MX is used as hormone replacement therapy (HRT) to relieve the symptoms of the menopause. The menopause can occur naturally or as the result of surgery.

Estraderm MX 50 and 75 patches can also be used to prevent osteoporosis (thinning of the bones), when you have a high risk of future fractures, and if you are unable to take other medicines for this purpose.

To relieve the symptoms of the menopause:

Estraderm MX is used to help relieve the uncomfortable symptoms which you sometimes get during and after the menopause (the time when menstrual periods stop). Menopause occurs naturally in all women, usually between the ages of 45 and 55. It also occurs in younger women who have had their ovaries removed by surgery. The reduced levels of estrogen can cause unpleasant symptoms such as hot face, neck and chest, hot flushes (sudden waves of heat and sweating all over), sleep problems, irritability and depression.

Some women also have problems with urine control, or with a dry vagina which may cause discomfort during or after sexual intercourse. Taking estrogens can reduce or eliminate these symptoms.

To prevent osteoporosis:

After the age of 40, and especially after the menopause, some women are at risk of developing osteoporosis. This is when the bones become thinner and weaker and more likely to break, especially the bones of the spine, hip and wrist. Lack of estrogens increases the risk of osteoporosis. Taking estrogens after the menopause slows down bone loss and can help to prevent it. The protective effects on the bone cease once treatment is stopped. You should discuss the benefits and risks of Estraderm MX and other therapies with your doctor.

Things to consider before you start to use Estraderm MX

Read this section carefully because, there are some conditions your doctor should know about before you start your treatment.

Medical check-ups

Before you start using HRT, your doctor should ask you about your own, and your family’s, medical history. Your doctor may decide to examine your breasts and/or your abdomen and may do an internal examination - but only if these examinations are necessary for you, or you have any special concerns. Once you have started HRT, you should see your doctor for regular check-ups (at least once a year). At these check-ups your doctor may discuss with you the benefits and risks of continuing with HRT.

While you are using HRT make sure that you:

Go for regular breast screening and cervical smear tests. Regularly check your breasts for any changes such as dimpling of the skin, changes in the nipple, a discharge from the nipple, or any lumps you can see or feel.

Some people MUST NOT use Estraderm MX. Talk to your doctor if:

you have ever had any unusual or allergic reaction to estrogens or to any other components of the patch, (These are listed at the end of the leaflet.) you have, or have ever had, breast cancer, (See the section below on breast cancer.) you have, or have ever had, cancer of the endometrium (lining of the womb) or any other cancer which is sensitive to estrogens, (See the sections below on endometrial and ovarian cancer.) you have a blood disease called porphyria, you have, or have ever had, a blood clot in a vein in your leg or anywhere else (a deep vein thrombosis) or a clot that has travelled to your lung or another part of your body (an embolus), (See the section below on blood clots.) you have ever had a heart attack, stroke or angina, (See the sections below on heart disease and stroke.) you have had any unexpected bleeding or very heavy bleeding from the vagina, you have a history of liver disease, you have a condition called endometrial hyperplasia (thickening of the lining of the womb), you are pregnant or breastfeeding.
Estraderm MX should not be used in children.

You should also ask yourself these questions before using the patch. If the answer to any of these questions is YES, tell your doctor or pharmacist because Estraderm MX might not be the right medicine for you.

Has anyone in your immediate family had breast cancer? Do you have fibroids or any other growths in your womb? Have you had a hysterectomy? Do you have endometriosis (a condition which causes painful periods)? Do you have high blood pressure? Do you have any problems with your liver? Do you have diabetes, epilepsy or asthma? Do you get migraine or other bad headaches? Do you have a condition called lupus (SLE)? Do you have problems with your hearing? Do you have any of the conditions which put you at increased risk of blood clots (see below)? Do you have a high level of cholesterol or other fats in your blood? Do you have heart or kidney problems? Have you ever had problems with your gall bladder, such as gallstones? Are you over 65? Are you taking other medicines?

Some medicines can interfere with your treatment. Tell your doctor or pharmacist if you are taking any of the following:

medicines to treat epilepsy such as phenobarbital, phenytoin and carbamazepine, antibiotics and other medicines to treat infections (e.g. rifampicin, rifabutin, nevirapine, efavirenz, ritonavir, nelfinavir), the herbal medicine St John’s Wort (also known as Hypericum perforatum).

Always tell your doctor or pharmacist about all the medicines you are taking. This means medicines you have bought yourself as well as medicines on prescription from your doctor.

Before you have a blood test remind your doctor that you are using Estraderm MX as it may affect the result.

Will there be any problems with driving or using machinery?

No problems have been reported.

Using contraception whilst taking Estraderm MX

Estraderm MX is not a contraceptive, nor a fertility treatment.

If you are using an oral or other hormone contraceptive, e.g. the pill or depot injection, you must change to a non-hormone contraceptive, for example, a diaphragm or condom, BEFORE starting Estraderm MX.

If you have been told that you don’t need to use a contraceptive any longer, you won’t need one while you are using Estraderm MX even if you have a monthly bleed.

Other special warnings

HRT will not help to prevent heart disease.

As well as benefits, HRT has some risks which you need to consider when you are deciding whether to use it, or whether to carry on using it. These are:

Effects on your heart or circulation

i. Heart disease

HRT is not recommended for women who have heart disease, or have had heart disease recently. If you have ever had heart disease, talk to your doctor to see if you should be using HRT.

Studies with one type of HRT (containing conjugated estrogen plus a progestogen) have shown that women may be slightly more likely to get heart disease during the first year of taking the medication. For other types of HRT, the risk is likely to be similar, although this is not yet certain.

If you get:

A pain in your chest that spreads to your arm or neck,

See a doctor as soon as possible and do not use any more HRT until your doctor says you can. This pain could be a sign of heart disease.

ii. Stroke

Recent research suggests that HRT slightly increases the risk of having a stroke. Other things that can increase the risk of stroke include:

Getting older High blood pressure Smoking Drinking too much alcohol An irregular heartbeat

If you are worried about any of these things, or if you have had a stroke in the past, talk to your doctor to see if you ought to be using HRT.

If you get:

Unexplained migraine-type headaches, with or without disturbed vision,

See a doctor as soon as possible and do not use any more HRT until your doctor says you can. These headaches may be an early warning sign of a stroke.

iii. Blood clots

Using HRT may increase the risk of blood clots in the veins (also called deep vein thrombosis, or DVT), especially during the first year. These blood clots are not always serious, but if one travels to the lungs, it can cause chest pain, breathlessness, collapse or even death. This condition is called pulmonary embolism, or PE.

DVT and PE are examples of a condition called venous thromboembolism, or VTE.

You are more likely to get a blood clot if:

You are seriously overweight You have had a blood clot before Any of your close family have had blood clots You have had one or more miscarriages You have any blood clotting problem that needs treatment with a medicine such as warfarin You’re off your feet for a long time because of major surgery, injury or illness You are going on a long journey and will be immobile for some time You have a rare condition called systemic lupus erythematosus (SLE – a connective tissue disease).

If any of these things apply to you, talk to your doctor to see if you should be using HRT.

If you get:

Painful swelling in your leg Sudden chest pain Difficulty breathing

See a doctor as soon as possible and do not use any more HRT until your doctor says you can. These may be signs of a blood clot.

If you’re going to have surgery, make sure your doctor knows about it. You may need to stop using HRT about 4 to 6 weeks before the operation, to reduce the risk of a blood clot. Your doctor will tell you when you can start using HRT again.

A comparison – the approximate risk of stroke or blood clots in women not using, or using, HRT over a 5 year period

Women in their 50s
Stroke has been reported in 3 in 1,000 women not using HRT, compared to 4 in 1,000 women using HRT.
Blood clots have been reported in 3 in 1,000 women not using HRT, compared to 7 in 1,000 women using HRT.

Women in their 60s
Stroke has been reported in 11 in 1,000 women not using HRT, compared to 15 in 1,000 women using HRT.
Blood clots have been reported in 8 in 1,000 women not using HRT, compared to 17 in 1,000 women using HRT.

Effects on your risk of developing cancer

i. Breast cancer

Women who have breast cancer, or have had breast cancer in the past, should not use HRT.

Using HRT slightly increases the risk of breast cancer; so does having a late menopause.

The risk for a post-menopausal woman using estrogen-only HRT for 5 years is about the same as for a woman of the same age who’s still having periods over that time and not using HRT. The risk for a woman who is using combined HRT (estrogen plus progestogen) is higher than for estrogen-only HRT (but combined HRT is beneficial for the endometrium, see Endometrial cancer, below).

For all kinds of HRT, the extra risk of breast cancer goes up the longer you use it, but returns to normal within about 5 years of stopping HRT.

Your risk of breast cancer is also higher if:

You have a close relative (mother, sister or grandmother) who has had breast cancer You are seriously overweight.

If you notice any changes in your breast, such as:

Dimpling of the skin Changes in the nipple or a discharge from the nipple Any lumps you can see or feel

Make an appointment to see your doctor as soon as possible.

A comparison – the risk of developing breast cancer: the number of women aged 50 who will get breast cancer by the time they are 65.

32 in 1,000 of these women who are not using HRT, will get breast cancer.
33.5 in 1,000 of these women who have used estrogen-only HRT for 5 years, will get breast cancer.
37 in 1,000 of these women who have used estrogen-only HRT for 10 years, will get breast cancer.
38 in 1,000 of these women who have used combined HRT for 5 years, will get breast cancer.
51 in 1,000 of these women who have used combined HRT for 10 years, will get breast cancer.

ii. Endometrial cancer (cancer of the lining of the womb)

Estraderm MX is an estrogen-only product.

Using estrogen-only HRT for a long time can increase the risk of cancer of the lining of the womb. Taking a progestogen as well as the estrogen helps to lower the extra risk.

If you still have your womb, your doctor may prescribe a progestogen as well as estrogen.

They can be prescribed separately, or as a combined HRT product.

If you have had your womb removed (a hysterectomy), your doctor will discuss with you whether you can safely take estrogen without a progestogen.

If you’ve had your womb removed because of endometriosis, any endometrium left in your body may be at risk. So your doctor may prescribe HRT that includes a progestogen as well as an estrogen.

A comparison – the risk of developing endometrial cancer

Women who still have their uterus and who do not use HRT

About 5 in 1,000 women aged 50 will get endometrial cancer by the time they are 65.

Women who have used estrogen-only HRT

The number will be 2-12 times higher depending on the dose and length of use.

Women who have used estrogen plus progestogen HRT

The risk of endometrial cancer is substantially reduced.

If you get breakthrough bleeding or spotting, it’s usually nothing to worry about, especially during the first few months of taking HRT.

But if the bleeding or spotting:

Carries on for more than the first few months Starts after you’ve been on HRT for a while Carries on even after you’ve stopped using HRT

Make an appointment to see your doctor. It could be a sign that your endometrium has become thicker.

iii. Ovarian cancer (cancer of the ovaries)

Cancer of the ovaries is very rare, but it is serious. It can be difficult to diagnose, because there are often no obvious signs of the disease.

Some studies have indicated that using estrogen-only HRT for more than 5 years may increase the risk of ovarian cancer. It is not yet known whether other kinds of HRT increase the risk in the same way.

Effects on your risk of developing dementia

HRT will not prevent memory loss. In one study of women who started using combined HRT after the age of 65, a small increase in risk of dementia was observed.

How to use Estraderm MX patches

The doctor will tell you how to use Estraderm MX and what dose you need. Always follow his/her instructions carefully. The information will be on the pharmacist’s label.

Check the label carefully. If you are not sure, ask your doctor or pharmacist. Do not change the dose or stop the treatment without talking to your doctor.

If you have not had a hysterectomy, your doctor will give you tablets containing another hormone called progestogen to offset the effects of estrogens on the lining of the womb. (See the section above on endometrial cancer.) Your doctor will explain to you how to take these tablets. Withdrawal bleeding may occur at the end of the progestogen treatment period. Tell your doctor if you get irregular and/or heavy bleeding (see endometrial cancer).

Starting to use the patches

Estraderm MX patches are applied to the skin. You wear them all the time. You should apply a new patch twice a week i.e. every 3 or 4 days.

If you are not currently using any form of HRT (patch or tablets), if you have had a hysterectomy or if you have been using a continuous combined HRT product (where estrogen and the progestogen are given every day without interruption), you can start to use Estraderm MX on any convenient day. If you are changing from a cyclic or sequential HRT treatment where the progestogen is added for 12-14 days of the cycle, start to use Estraderm MX the day after you complete the cycle. If you are still having periods you should start to use Estraderm MX within 5 days of starting your period, irrespective of how long you bleed. About the patch

Where to apply the patch

Stick the patch on to a hairless area of skin below the waist. Most patients find that the buttock is the best place. Choose an area of the buttock where the skin is not inflamed, broken, or irritated. You could also try the lower back, hip or abdomen.

Never put a patch on or near the breasts.

Choose a clean, dry area of skin. To help the patch stick, the skin should be clean, dry, and free of creams, lotions, oil, or powder. You should use a different area of skin each time. Wait a week before using the same area again. Avoid skin which is red or irritated.

Do not expose the patch to direct sunlight.

Opening the sachets

Each Estraderm MX patch is sealed in an airtight sachet. Tear open one of the sachets at the notch (do not use scissors) and take out the patch. Don’t take the patch out of the sachet until immediately before you intend to use it.

Removing the lining

A stiff, transparent protective lining covers the sticky side of the patch, i.e. the side that will be placed against your skin. First remove the smaller piece of the transparent liner. Then peel off the larger piece. Try to avoid touching the adhesive and remember not to allow the patch to become folded so that the sticky surfaces come in contact with each other. Now apply the patch.

Applying the patch

With the palm of your hand press the sticky side of the patch firmly onto the spot you have chosen. Hold it there for about 10-20 seconds. Make sure that it sticks well, especially around the edges, but once the patch is in place do not pull at it to test that it is sticking properly.

When and how to remove the patch

The patches should be changed twice a week on the same two days of the week, e.g. Mondays and Thursdays. Choose two days which you are likely to remember.

Note the day of the week on which you are starting the treatment.

When the time comes to change the patch, peel it off and fold it in half with the sticky side inside. Dispose of the patch carefully (see Section 5), making sure that it is kept out of the reach of children because it will still contain some medication. Stick a new patch onto a different area of skin.

What to do if a patch comes off

If a patch falls off it will not stick to your skin again. Use another patch on a different area of your skin (see Where to apply the patch). Make sure you choose a clean, dry, lotion-free area of the skin. No matter what day this happens, go back to changing the patch on the same days as usual.

Other useful information Bathing, swimming, showering or exercising should not affect the patch if it has been correctly applied. You may wear the patch under your swimming costume. Never apply a patch on a sweaty area or after a hot bath or shower. Wait until the skin is completely cool and dry. Do not remove the patch and try to put it somewhere else, it will not stick to your skin again. Instead apply a new patch in the usual way. Remember to apply your next patch at the normal time. If you have run out of patches, please contact your doctor straight away. (See also advice on What to do if a patch comes off.) Sunbathing: always make sure your patch is covered by clothing. Using a sunbed: cover up the patch The drug in your patch is contained in the adhesive and not in a special reservoir. The drug in your patch is a gel which is colourless. This does not mean that the patch does not contain any medication. How long to use Estraderm MX

Estraderm MX should be used only as long as needed, possibly for several months or more. This will help to control your symptoms.

While you are using Estraderm MX you should go to the doctor regularly to discuss the possible risks and benefits associated with HRT, and whether you still need the treatment.

Your doctor will aim to give you the lowest possible dose for the shortest possible length of time to treat your symptoms.

If you forget to use Estraderm MX

If you forget to apply a patch, apply a new patch as soon as you remember. No matter what day that happens, go back to changing this patch on the same day as you usually do.

There is an increased chance of breakthrough bleeding or spotting if there is a break in treatment.

Estraderm MX Side Effects

Estraderm MX is suitable for most people, but, like all medicines, there are sometimes side effects.

Stop using Estraderm MX immediately and tell your doctor if you develop any of the following: Signs of an allergic reaction (difficulty in breathing, tight chest, itching all over, generalised swelling or itching). Migraine or unusually severe headaches, or signs of stroke You become pregnant Signs of jaundice (yellowing of your skin or eyes). The side effects listed below have also been reported:

Up to 1 in 10 people have experienced:

Headache Feeling sick or bloated, stomach ache Redness and itching where the patch has been applied Tender or painful breasts Breakthrough bleeding.

Up to 1 in 100 people have experienced:

Breast cancer.

Up to 1 in 1,000 people have experienced:

Dizziness Blood clots, bruising, worsening varicose veins, raised blood pressure Abnormal liver function test results, jaundice Rash and itching over large areas of the skin. This sensitivity reaction may become severe if you carry on using the patches without talking to your doctor. Changes in the pigmentation in your skin (lightening or darkening of your skin colour) Unusual weight changes, fluid retention (swelling or accumulation of fluid in the lower legs or ankles), leg pain. Other side effects include: Estrogen-dependent conditions such as cancer of the endometrium, heart attack, stroke, dementia (these are discussed in Section 2) and gall bladder disease.

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are using Estraderm MX. Ask your doctor or pharmacist to answer any questions you may have.

How to store the patches

Keep Estraderm MX out of the reach and sight of children both before and after use.

Store below 25°C, away from direct sunlight.

Do not use Estraderm MX after the expiry date shown on the pack.

Do not use a new Estraderm MX pack that is damaged or shows signs of tampering.

If your doctor tells you to stop using Estraderm MX, please take any patches left back to your pharmacist to be destroyed. Only keep them if the doctor tells you to. Do not throw them away with your normal household water or waste. This will help to protect the environment.

Further information

The active substance in Estraderm MX is estradiol. The estradiol is derived from plants and is produced synthetically.

The other ingredients in Estraderm MX are isopropyl palmitate, acrylic adhesive (in solution in ethylacetate/hexane) and ethyl acetate. The backing film consists of ethylene vinyl acetate/polyester film laminate. The protective liner, which is removed before the patch is used, is a siliconized polyester film. The estradiol is released gradually while you are wearing the patch.

Estraderm MX 25 contains 0.75 mg estradiol releasing about 25 micrograms of estradiol a day.

Estraderm MX 50 contains 1.5 mg estradiol releasing about 50 micrograms of estradiol a day.

Estraderm MX 75 contains 2.25 mg estradiol releasing about 75 micrograms of estradiol a day.

Estraderm MX 100 contains 3.0 mg estradiol releasing about 100 micrograms of estradiol a day.

A one month pack contains 8 patches; a 3-month pack contains 24 patches of one size.

The product licence holder is Novartis Pharmaceuticals UK Limited Frimley Business Park Frimley Camberley Surrey GU16 7SR England Estraderm MX patches are made by Lohmann LTS Lohmannstr. 2 P.O. Box 1525 56605 Andernach Germany

This leaflet was revised in December 2008.

Fill this in to remind you when to change your patch. Please tick the box for the days of the week when you should change your patch.

Monday + Thursday Tuesday + Friday Wednesday + Saturday Thursday + Sunday Friday + Monday Saturday + Tuesday Sunday + Wednesday

If you would like any more information, or would like the leaflet in a different format, please contact Medical Information at Novartis Pharmaceuticals UK Ltd, telephone number 01276 698370.

ESTRADERM MX is a registered trade mark

Copyright Novartis Pharmaceuticals UK Limited


read more


Related Search: