Childrens Cetirizine Oral Solution



CHILDREN'S
CETIRIZINE
HYDROCHLORIDE
ORAL SOLUTION
1 mg/1 mL
Antihistamine

Drug Facts

Active ingredient (in each 5 mL teaspoonful)

Cetirizine HCl 5 mg

Purpose

Antihistamine

Uses

Temporarily relieves these symptoms due to hay fever or other upper respiratory allergies:

runny nose itchy, watery eyes sneezing itching of the nose or throat Warnings

Do not use if you have ever had an allergic reaction to this product or any of its ingredients or to an antihistamine containing hydroxyzine.

Ask a doctor before use if you have liver or kidney disease. Your doctor should determine if you need a different dose.

Ask a doctor or pharmacist before use if you are taking tranquilizers or sedatives.

When using this product drowsiness may occur avoid alcoholic drinks alcohol, sedatives, and tranquilizers may increase drowsiness be careful when driving a motor vehicle or operating machinery

Stop use and ask a doctor if an allergic reaction to this product occurs. Seek medical help right away.

If pregnant or breast-feeding:

if breast-feeding: not recommended if pregnant: ask a health professional before use.

Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center right away.

Directions use only with enclosed dosing cup adults and children 6 years and over 1 teaspoonful (5 mL) or 2 teaspoonfuls (10 mL) once daily depending upon severity of symptoms; do not take more than 2 teaspoonfuls (10 mL) in 24 hours. adults 65 years and older 1 teaspoonful (5 mL) once daily; do not take more than 1 teaspoonful (5 mL) in 24 hours. children 2 to under 6 years of age 1/2 teaspoonful (2.5 mL) once daily. If needed, dose can be increased to a maximum of 1 teaspoonful (5 mL) once daily or 1/2 teaspoonful (2.5 mL) every 12 hours. Do not give more than 1 teaspoonful (5 mL) in 24 hours. children under 2 years of age ask a doctor consumers with liver or kidney disease ask a doctor Other information store between 20° to 25°C (68° to 77°F) Inactive ingredients

artificial grape flavor, glacial acetic acid, glycerin, methylparaben, natural and artificial banana flavor, propylene glycol, propylparaben, purified water, sodium acetate (anhydrous), sucrose

Questions?

Call 1-866-923-4914

Distributed by: Chain Drug Consortium, LLC
2300 NW Corporate BLVD., Suite 115
Boca Raton, FL 33431
Made in Israel

PRINCIPAL DISPLAY PANEL - 120 mL bottle carton

NDC 68016-023-43

Ages
two years
and older

Compare to
the active ingredient
in Children's Zyrtec®*

Premier
Value®

CHILDREN'S
CETIRIZINE
HYDROCHLORIDE
ORAL SOLUTION
1 mg/1 mL
Antihistamine

Grape Flavored Syrup

24 hour Allergy Relief of:
Sneezing; Runny Nose;
Itchy,Watery Eyes;
Itchy Throat or Nose

Indoor & Outdoor Allergies

Dosing Cup
Included

PV
PREMIER VALUE GUARANTEE

4 FL OZ (120 mL)


CHILDRENS CETIRIZINE HYDROCHLORIDE 
cetirizine hydrochloride  solution Product Information Product Type HUMAN OTC DRUG NDC Product Code (Source) 68016-023 Route of Administration ORAL DEA Schedule      Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Cetirizine Hydrochloride (Cetirizine) Cetirizine Hydrochloride 5 mg  in 5 mL Inactive Ingredients Ingredient Name Strength acetic acid   glycerin   methylparaben   propylene glycol   propylparaben   water   sodium acetate anhydrous   sucrose   Product Characteristics Color YELLOW (colorless to slightly yellow) Score      Shape Size Flavor GRAPE, BANANA Imprint Code Contains          Packaging # NDC Package Description Multilevel Packaging 1 68016-023-43 1 BOTTLE In 1 CARTON contains a BOTTLE 1 120 mL In 1 BOTTLE This package is contained within the CARTON (68016-023-43)
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA090182 04/22/2008
Labeler - Chain Drug Consortium, LLC (Premier Value) (101668460) Registrant - Taro Pharmaceuticals U.S.A., Inc. (145186370) Establishment Name Address ID/FEI Operations Taro Pharmaceutical Industries Ltd. 600072078 ANALYSIS, MANUFACTURE Revised: 04/2010Chain Drug Consortium, LLC (Premier Value)
More Childrens Cetirizine Oral Solution resources Childrens Cetirizine Oral Solution Side Effects (in more detail) Childrens Cetirizine Oral Solution Use in Pregnancy & Breastfeeding Drug Images Childrens Cetirizine Oral Solution Drug Interactions Childrens Cetirizine Oral Solution Support Group 73 Reviews for Childrens Cetirizine - Add your own review/rating Compare Childrens Cetirizine Oral Solution with other medications Hay Fever Urticaria
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Carnitor 330 mg Tablets


1. Name Of The Medicinal Product

Carnitor 330 mg Tablets

2. Qualitative And Quantitative Composition

Each tablet contains L-Carnitine inner salt 330 mg

For a full list of excipients, see section 6.1.

3. Pharmaceutical Form

White, round, standard biconvex tablets, approximately 13 mm diameter.

4. Clinical Particulars 4.1 Therapeutic Indications

Indicated for the treatment of primary and secondary carnitine deficiency in adults and children over 12 years of age.

4.2 Posology And Method Of Administration

For oral administration only.

Adults and children over 12 years of age

The tablets should be given in divided doses.

It is advisable to monitor therapy by measuring free and acyl carnitine levels in both plasma and urine.

The management of inborn errors of metabolism

The dosage required depends upon the specific inborn error of metabolism concerned and the severity of presentation at the time of treatment. However, the following can be considered as a general guide.

An oral dosage of up to 200mg/kg/day in divided doses (2 to 4) is recommended for chronic use in some disorders, with lower doses sufficing in other conditions. If clinical and biochemical symptoms do not improve, the dose may be increased on a short-term basis. Higher doses of up to 400mg/kg/day may be necessary in acute metabolic decompensation or the i.v. route may be required.

Haemodialysis - maintenance therapy

If significant clinical benefit has been gained by a first course of intravenous Carnitor then maintenance therapy can be considered using 1 g per day of Carnitor orally. On the day of the dialysis oral Carnitor has to be administered at the end of the session.

4.3 Contraindications

Hypersensitivity to any constituent of the product.

4.4 Special Warnings And Precautions For Use

While improving glucose utilisation, the administration of L-carnitine to diabetic patients receiving either insulin or hypoglycaemic oral treatment may result in hypoglycaemia. Plasma glucose levels must be monitored regularly in order to adjust the hypoglycaemic treatment immediately, if required.

The safety and efficacy of oral L-carnitine has not been evaluated in patients with renal insufficiency. Chronic administration of high doses of oral L-carnitine in patients with severely compromised renal function or in end stage renal disease (ESRD) patients on dialysis may result in an accumulation of the potentially toxic metabolites, trimethylamine (TMA) and trimethylamine-N-oxide (TMAO), since these metabolites are usually excreted in the urine. This situation has not been observed following intravenous administration of L-carnitine.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

There are no known interactions.

4.6 Pregnancy And Lactation

Reproductive studies were performed in rats and rabbits. There was no evidence of a teratogenic effect in either species. In the rabbit but not in the rat there was a statistically insignificant greater number of post implantation losses at the highest dose tested (600mg/kg daily) as compared with control animals. The significance of these findings in man is unknown. There is no experience of use in pregnant patients with primary systemic carnitine deficiency. Taking into account the serious consequences in a pregnant woman who has primary systemic carnitine deficiency stopping treatment, the risk to the mother of discontinuing treatment seems greater than the theoretical risk to the foetus if treatment is continued.

Levocarnitine is a normal component of human milk. Use of levocarnitine supplementation in nursing mothers has not been studied.

4.7 Effects On Ability To Drive And Use Machines

None known.

4.8 Undesirable Effects

Various mild gastro-intestinal complaints have been reported during the long term administration of oral levocarnitine, these include transient nausea and vomiting, abdominal cramps and diarrhoea.

Decreasing the dosage often diminishes or eliminates drug related patient body odour or gastro-intestinal symptoms when present. Tolerance should be monitored very closely during the first week of administration and after any dosage increase.

4.9 Overdose

There have been no reports of toxicity from levocarnitine overdosage. Overdosage should be treated with supportive care.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

ATC Code: A16AA01 (Amino acids and derivatives)

L-Carnitine is present as a natural constituent in animal tissues, micro-organisms and plants. In man the physiological metabolic requirements are met both by the consumption of food containing carnitine and the endogenous synthesis in the liver and kidneys from lysine with methionine serving as the methyl donor. Only the L-isomer is biologically active, playing an essential role in lipid metabolism as well as in the metabolism of ketone bodies as branched chain-amino-acids. L-Carnitine as a factor is necessary in the transport of long-chain fatty acids into the mitochondria - facilitating the oxidation of fatty acids rather than their incorporation into triglycerides. By releasing CoA from its thioesters, through the action of CoA; carnitine acetyl transferase, L-carnitine also enhances the metabolic flux in the Kreb's cycle; with the same mechanism it stimulates the activity of pyruvate dehydrogenase and in skeletal muscle, the oxidation of branched-chain amino acids. L-Carnitine is thus involved, directly or indirectly in several pathways so that its availability should be an important factor controlling not only the oxidative utilisation of fatty acids and ketone bodies but also that of glucose and some amino acids.

5.2 Pharmacokinetic Properties

The absorbed L-carnitine is transported to various organ systems via the blood. The presence of membrane-bound proteins in several tissues including red blood cells that bind carnitine, suggest that a transport system in the blood and a cellular system for the collective uptake is present in several tissues. Tissue and serum carnitine concentration depend on several metabolic processes, carnitine bio-synthesis and dietary contributions, transport into and out of tissues, degradation and excretion may all affect tissue carnitine concentrations. Following administration, studies have demonstrated that a peak concentration of 71.89±5.13 ?M was achieved 6 hours after dosing. The pharmacokinetic parameters showed an absorption phase half life of 1.45 hours and an elimination phase with a half-life of 3.34 hours. The apparent bioavailability was 14%.

The urinary recovery in 14 hours was 6.02% of the administered dose.

5.3 Preclinical Safety Data

L-Carnitine is a naturally occurring body substance in human beings, plants and animals. Carnitor products are used to bring the level of L-carnitine in the body up to those found naturally. Appropriate pre-clinical studies have been undertaken and show no signs of toxicity at normal therapeutic levels.

6. Pharmaceutical Particulars 6.1 List Of Excipients

Magnesium stearate (E572)

Polyvinylpyrrolidone

Microcrystalline cellulose (E460).

6.2 Incompatibilities

None known.

6.3 Shelf Life

Unopened shelf life of 60 months (5 years).

6.4 Special Precautions For Storage

Store below 25°C.

6.5 Nature And Contents Of Container

Blister packed in quantities of 30, 90, 100 and 180.

6.6 Special Precautions For Disposal And Other Handling

No special instructions.

7. Marketing Authorisation Holder

Sigma-Tau Industrie Farmaceutiche Riunite SpA,

Viale Shakespeare 47-00144,

Rome, Italy.

8. Marketing Authorisation Number(S)

PL 08381/0002

9. Date Of First Authorisation/Renewal Of The Authorisation

15 August 1990

15 October 2000

10. Date Of Revision Of The Text

February 2009


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Occlusal


1. Name Of The Medicinal Product

Occlusal.

26% w/w cutaneous solution

2. Qualitative And Quantitative Composition

Salicylic Acid 26% w/w.

For excipients, see 6.1

3. Pharmaceutical Form

Cutaneous solution

A colourless to pale yellow solution with a characteristic smell of nail varnish

4. Clinical Particulars 4.1 Therapeutic Indications

Occlusal is indicated for the treatment and removal of common and plantar warts (verrucae).

4.2 Posology And Method Of Administration

For topical application.

Prior to application soak wart in warm water for five minutes. Remove loose tissue with a brush, emery board, pumice or abrasive sponge, being careful to avoid causing pin-point bleeding or abrading the surrounding healthy skin. Dry thoroughly with a towel not used by others to avoid contagion. Carefully apply Occlusal twice to the wart using the brush applicator allowing the first application to dry before applying the second. Thereafter repeat treatment once daily or as directed by physician. Do not apply to surrounding healthy skin. Clinically visible improvement should occur in one to two weeks but maximum effect may be expected after four to six weeks.

There are no differences in dosage for children, adults or the elderly.

4.3 Contraindications

Hypersensitivity to salicylic acid or to any of the excipients.

Occlusal should not be used by diabetics or patients with impaired blood circulation. Do not use if the wart or surrounding skin is inflamed or broken. Do not use on moles, birthmarks, unusual warts with hair growth, on facial warts, or in the anal or perineal region.

4.4 Special Warnings And Precautions For Use

Occlusal is for external use only. Do not permit contact with eyes or mucous membranes. If contact occurs flush with water for 15 minutes. Do not allow contact with normal skin around wart. Avoid using on areas of broken or damaged skin. Discontinue treatment if excessive irritation occurs. Excessive prolonged use of topical salicylic acid may result in symptoms of salicylism and must therefore be avoided.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

There are no known interactions when used as indicated. However, topical salicylic acid may increase the absorption of other topically applied medicines. Concomitant use of Occlusal and other topical medicines on the treated wart should therefore be avoided.

4.6 Pregnancy And Lactation

Whilst there are no known contra-indications to use of Occlusal during pregnancy and lactation, the safety has not been established. Occlusal should therefore be used with caution or following professional advice.

4.7 Effects On Ability To Drive And Use Machines

None known.

4.8 Undesirable Effects

A localised irritant reaction may occur if Occlusal is applied to normal skin surrounding the wart. This may normally be controlled by temporarily discontinuing the use of Occlusal and by being careful to apply the solution only to the wart itself when treatment is resumed.

4.9 Overdose

Symptoms of systemic salicylate poisoning have been reported after the application of salicylic acid to large areas of skin and for prolonged periods. Salicylism may also occur in the unlikely event of large quantities being ingested. Salicylism is unlikely to occur if Occlusal is used as indicated.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Wart and anticorn preparations

ATC code: D11AF

Salicylic acid has bacteriostatic and fungicidal actions, but it is its keratolytic properties which are important for this medicinal product. When applied externally it produces slow and painless destruction of the epithelium. Salicylic acid is usually applied in the form of a paint in a collodian base (10 to 17%) or as a plaster (20 to 50%) to destroy warts or corns.

5.2 Pharmacokinetic Properties

Salicylic acid may be percutaneously absorbed. However, there is no evidence of any systemic absorption from the use of Occlusal.

5.3 Preclinical Safety Data

No other information relevant to the prescriber other than that already stated in other sections of the SPC.

6. Pharmaceutical Particulars 6.1 List Of Excipients

Polyvinyl butyral

Dibutyl phthalate

Isopropyl alcohol

Butyl acetate

Acrylates copolymer

6.2 Incompatibilities

Not applicable

6.3 Shelf Life

2 years.

6.4 Special Precautions For Storage

Do not store above 25°C

6.5 Nature And Contents Of Container

The product is presented in a 10ml amber glass bottle with cap brush assembly. The cap brush assembly comprises of a black cap and a white polythene wand nylon brush with stainless steel staple.

6.6 Special Precautions For Disposal And Other Handling

Occlusal is flammable and should be kept away from flame or fire. Keep the bottle tightly capped when not in use. Do not allow the solution to drip from the brush onto the bottle neck thread, otherwise subsequent opening of the bottle may be difficult.

7. Marketing Authorisation Holder

Alliance Pharmaceuticals Limited

Avonbridge House

2 Bath Road

Chippenham

Wiltshire, SN15 2BB

UK

8. Marketing Authorisation Number(S)

PL 16853/0071

9. Date Of First Authorisation/Renewal Of The Authorisation

7th September 1998/18th May 2005

10. Date Of Revision Of The Text

28th April 2011


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Cobalin-H Injection (Amdipharm Plc)


1. Name Of The Medicinal Product

Cobalin-H

2. Qualitative And Quantitative Composition

Anhydrous hydroxocobalamin 1000mcg/ml.

3. Pharmaceutical Form

Injection

4. Clinical Particulars 4.1 Therapeutic Indications

Treatment of Addisonian pernicious anaemia.

Prophylaxis and treatment of other macrocytic anaemias due to vitamin B12 deficiency.

Treatment of tobacco amblyopia.

Treatment of Leber's atrophy.

4.2 Posology And Method Of Administration

The following dosages are suitable for children and adults.

Addisonian pernicious anaemia and other macrocytic anaemias without neurological involvement:

Initially:

250 micrograms to 1000 micrograms intramuscularly on alternate days for one or two weeks then 250 micrograms weekly until blood count is normal.

Maintenance:

1000 micrograms every two or three months.

Addisonian pernicious anaemia and other macrocytic anaemias with neurological involvement:

Initially:

1000 micrograms on alternate days as long as improvement continues.

Maintenance:

1000 micrograms every two months.

Prophylaxis of macrocytic anaemias associated with vitamin B12 deficiency resulting from gastrectomy, ileal resection, certain ma/absorption states and vegetarianism:

1000 micrograms every two or three months.

Tobacco amblyopia and Leber's optic atrophy:

Initially:

1000 micrograms daily by intramuscular injection for two weeks then twice weekly as long as improvement is maintained.

Maintenance:

1000 micrograms every three months or as required.

4.3 Contraindications

Sensitivity to hydroxocobalamin / vitamin B12.

4.4 Special Warnings And Precautions For Use

Cobalin-H should not be given before a megaloblastic marrow has been demonstrated. Regular monitoring of the blood is advisable. Doses of hydroxocobalamin greater than 10 micrograms daily may produce a haematological response in patients with folate deficiency. Indiscriminate use may mask the exact diagnosis. Cardiac arrhythmias secondary to hypokalaemia have been reported during initial therapy and plasma potassium should, therefore, be monitored during this period.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

The serum concentration of hydroxocobalamin may be reduced by concurrent administration of oral contraceptives. Chlorphenicol-treated patients may respond poorly to hydroxocobalamin. Vitamin B12 assays by microbiological techniques are invalidated by antimetabolites and most antibiotics.

4.6 Pregnancy And Lactation

Hydroxocobalamin should not be used to treat megaloblastic anaemia of pregnancy.

4.7 Effects On Ability To Drive And Use Machines

None stated.

4.8 Undesirable Effects

The following effects have been reported and are listed below by body system:

Disorders of the immune system:

 

Rare:

Allergic hypersensitivity reactions

Very rare:

Anaphylaxis

Gastro intestinal disorders:

 

Frequency Not Known:

Nausea

General disorders:

 

Frequency Not Known:

Fever, dizziness, Injection site disorders

Neurological disorders:

 

Frequency Not Known:

Headache

4.9 Overdose

Treatment is unlikely to be needed in cases of overdosage.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

Vitamin B12

ATC classification: B03B A03

5.2 Pharmacokinetic Properties

Vitamin B12 is extensively bound to specific plasma proteins called transcobalamins; transcobalamin II appears to be involved in the rapid transport of the cobalamins to tissues. It is stored in the liver, excreted in the bile, and undergoes enterohepatic recycling; part of a dose is excreted in the urine, most of it in the first 8 hours.

5.3 Preclinical Safety Data

There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the Summary of Product Characteristics.

6. Pharmaceutical Particulars 6.1 List Of Excipients

Sodium dihydrogen orthophosphate

Sodium chloride

Water for Injections

6.2 Incompatibilities

None stated.

6.3 Shelf Life

60 months.

6.4 Special Precautions For Storage

Protect from light. Store below 25°C.

6.5 Nature And Contents Of Container

Cobalin-H is supplied in clear 1ml Type I glass ampoules in cartons of 5 or 10.

6.6 Special Precautions For Disposal And Other Handling

None stated.

7. Marketing Authorisation Holder

AMDIPHARM PLC

REGENCY HOUSE

MILES GRAY ROAD

BASILDON

ESSEX

SS14 3AF

UNITED KINGDOM

8. Marketing Authorisation Number(S)

PL 20072/0217

9. Date Of First Authorisation/Renewal Of The Authorisation

18th June 1993 / 6th November 1998

10. Date Of Revision Of The Text

18/05/2011


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MultiVit with Fluoride Chewable Tablets



Dosage Form: chewable tablets
Multi-Vitamin With Fluoride Chewable Tablets
Rx Only *Daily Value not established Supplement Facts Serving Size: 1 Chewable Tablet Amount Per Tablet % Daily Value Adults & children 4 years or more Vitamin A ................................. 2500 IU 50% Vitamin C ................................... 60 mg 100% Vitamin D .................................. 400 IU 100% Vitamin E .................................... 15 IU 50% Thiamin (B1) .......................... 1.05 mg 70% Riboflavin (B2) ......................... 1.2 mg 71% Niacin ..................................... 13.5 mg 68% Vitamin (B6) ........................... 1.05 mg 53% Folate ........................................ 0.3 mg 75% Vitamin B12 ............................ 4.5 mcg 75% Fluoride (as sodium fluoride) ... 1.0 mg *

Active ingredient for Caries Prophylaxis: Fluoride as Sodium Fluoride.

Other ingredients: Artificial grape flavor, ascorbic acid, butylated hydroxyl toluene, cholecalciferol, citric acid, compressible sugar, DL-alpha Tocopherol, D&C Red # 7 calcium lake, FD&C Blue #1 aluminum lake, folic acid, gelatin, magnesium stearate, maltodextrin, mannitol, medium chain triglycerides, methyl cellulose, mono- and di-glycerides, niacinamide, povidone, pyridoxine, riboflavin, silicon dioxide, sodium ascorbate, sodium citrate, starches, sucralose, thiamine, vitamin A acetate, vitamin B12 and vitamin E acetate.

CLINICAL PHARMACOLOGY

It is well established that fluoridation of the water supply (1 ppm fluoride) during the period of tooth development leads to a significant decrease in the incidence of dental caries.

Multi-vitamin with Fluoride Chewable Tablets provide sodium fluoride and ten essential vitamins in a chewable tablet. Because the tablets are chewable, they provide a topical as well as systemic source of fluoride.

Hydroxyapatite is the principal crystal for all calcified tissue in the human body. The fluoride ion reacts with the hydroxyapatite in the tooth as it is formed to produce the more caries-resistant crystal, fluorapatite. The reaction may be expressed by the equation:

Ca10(PO4)6(OH)2 + 2F-  —————> Ca10(PO4)6F2 + 2OH-

(Hydroxyapatite)                                   (Fluorapatite)

Three stages of fluoride deposition in tooth enamel can be distinguished:

1. Small amounts (reflecting the low levels of fluoride in tissue fluids) are incorporated into the enamel crystals while they are being formed.

2.  After enamel has been laid down, fluoride deposition continues in the surface enamel.  Diffusion of fluoride from the surface inward is apparently restricted.

3.  After eruption, the surface enamel acquires fluoride from the water, food, supplementary fluoride and smaller amounts from saliva.

INDICATIONS AND USAGE

Supplementation of the diet with ten essential vitamins.

Supplementation of the diet with fluoride for caries prophylaxis.

See Dosage and Administration.

Multi-vitamin with Fluoride Chewable Tablets supply significant amounts of Vitamins A, C, D, E, thiamin, riboflavin, niacin, vitamin B6, vitamin B12, and folate to supplement the diet, and to help assure that nutritional deficiencies of these vitamins will not develop. Thus, in a single easy-to-use preparation, children obtain ten essential vitamins and the important mineral, fluoride.

The American Academy of Pediatrics recommends that children up to age 16, in areas where drinking water contains less than optimal levels of fluoride, receive daily fluoride supplementation.

Children using Multi-vitamin with fluoride Chewable Tablets regularly should receive semiannual dental examinations. The regular brushing of teeth and attention to good oral hygiene practices are also essential.

WARNINGS

As in the case of all medications, keep out of the reach of children.

Should be chewed. This product, as all chewable tablets, is not recommended for children under age 4 due to risk of choking.

PRECAUTIONS

The suggested dose of Multi-vitamin with Fluoride Chewable Tablets should not be exceeded, since dental fluorosis may result from continued ingestion of large amounts of fluoride.

Before prescribing Multi-vitamin with Fluoride Chewable Tablets, read these Important Considerations When Using Dosage Schedule found in Dosage and Administration.

If fluoride level is unknown, drinking water should be tested for fluoride content before supplements are prescribed. For testing of fluoride content, contact the local or state health department. All sources of fluoride should be evaluated with a thorough fluoride history. Patient exposure to multiple water sources can make proper prescribing complex. Ingestion of higher than recommended levels of fluoride by children has been associated with an increase in mild dental fluorosis in developing, unerupted teeth. Fluoride supplements require long-term compliance on a daily basis. ADVERSE REACTIONS

Allergic rash and other idiosyncrasies have been rarely reported.

DOSAGE AND ADMINISTRATION *1.0 ppm = 1 mg / liter **2.2 mg Sodium Fluoride contains 1mg fluoride ion. Fluoride Ion Level in Drinking Water (ppm)* AGE <0.3 ppm 0.3-0.6 ppm >0.6 ppm 4-6 years 0.50 mg / day**
(1/2 tablet) 0.25 mg / day
(1/4 tablet) None 6-16 years 1.0 mg / day
(1 tablet) 0.50 mg / day
(1/2 tablet) None HOW SUPPLIED

Multi-vitamin 1 mg Sodium Fluoride Tablets: grape flavored, round, purple, debossed “BP 815”, available in 100 ct. bottle, NDC 64376-815-01.

Multi-vitamin 0.5 mg Sodium Fluoride Tablets: cherry flavored, square, red, debossed “BP 814”, available in 100 ct. bottle, NDC 64376-814-01.

Multi-vitamin 0.25 mg Sodium Fluoride Tablets: orange flavored, round, orange, debossed “BP 813”, available in 100 ct. bottle, NDC 64376-813-01.

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C -30°C (59°-86°F) [See USP Controlled Room Temperature].

Manufactured for:
Boca Pharmacal, Inc.
Coral Springs, FL 33065
www.bocapharmacal.com
1-800-354-8460 Iss. 07/11

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

[Rev 13]


MULTI-VITAMIN 
vitamin a, vitamin d, thiamine, riboflavin, niacin, pyridoxine, folic acid, fluoride ion, ascorbic acid, alpha-tocopherol-acetate-dl, cyanocobalamin  tablet, chewable Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 64376-815 Route of Administration ORAL DEA Schedule      Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength VITAMIN A (VITAMIN A) VITAMIN A 2500 [iU] VITAMIN D (VITAMIN D) VITAMIN D 400 [iU] THIAMINE (THIAMINE) THIAMINE 1.05 mg RIBOFLAVIN (RIBOFLAVIN) RIBOFLAVIN 1.2 mg NIACIN (NIACIN) NIACIN 13.5 mg PYRIDOXINE (PYRIDOXINE) PYRIDOXINE 1.05 mg FOLIC ACID (FOLIC ACID) FOLIC ACID 0.3 mg FLUORIDE ION (FLUORIDE ION) FLUORIDE ION 1.0 mg ASCORBIC ACID (ASCORBIC ACID) ASCORBIC ACID 60 mg .ALPHA.-TOCOPHEROL ACETATE, DL- (.ALPHA.-TOCOPHEROL ACETATE, DL-) .ALPHA.-TOCOPHEROL ACETATE, DL- 15 [iU] CYANOCOBALAMIN (CYANOCOBALAMIN) CYANOCOBALAMIN 4.5 ug Inactive Ingredients Ingredient Name Strength SODIUM CITRATE   CHOLECALCIFEROL   CYANOCOBALAMIN   FD&C BLUE NO. 1   FOLIC ACID   GELATIN   STARCH, CORN   MAGNESIUM STEARATE   MANNITOL   NIACINAMIDE   POVIDONE   PYRIDOXINE   GRAPE   RIBOFLAVIN   SILICON DIOXIDE   SODIUM ASCORBATE   THIAMINE   VITAMIN A ACETATE   ALPHA-TOCOPHEROL ACETATE   D&C RED NO. 7   ASCORBIC ACID   SUCRALOSE   BUTYLATED HYDROXYTOLUENE   CITRIC ACID MONOHYDRATE   .ALPHA.-TOCOPHEROL, DL-   MALTODEXTRIN   MEDIUM-CHAIN TRIGLYCERIDES   SUCROSE   GLYCERYL MONOSTEARATE   METHYLCELLULOSE (1500 CPS)   Product Characteristics Color PURPLE Score no score Shape ROUND (Biconvex) Size 13mm Flavor GRAPE Imprint Code BP;815 Contains          Packaging # NDC Package Description Multilevel Packaging 1 64376-815-01 100 TABLET In 1 BOTTLE None
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date Unapproved drug other 09/06/2011
Labeler - Boca Pharmacal, Inc (170266089) Registrant - Boca Pharmacal, Inc (170266089) Establishment Name Address ID/FEI Operations Cispharma, Inc 833171445 MANUFACTURE Revised: 09/2011Boca Pharmacal, Inc
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Multi Vitamin with Fluoride



Dosage Form: tablet, chewable
Unknown Title

Multi-Vitamin With Fluoride Chewable Tablets
Rx Only

*Daily Value not established Supplement Facts Serving Size: 1 Chewable Tablet Amount Per Tablet % Daily Value Adults & children 4 years or more Vitamin A .................................. 2500 IU 50% Vitamin C ..................................... 60 mg 100% Vitamin D .................................... 400 IU 100% Vitamin E ...................................... 15 IU 50% Thiamin (B1) ............................ 1.05 mg 70% Riboflavin (B2) ........................... 1.2 mg 71% Niacin ....................................... 13.5 mg 68% Vitamin (B6) ............................. 1.05 mg 53% Folate ......................................... 0.3 mg 75% Vitamin B12 .............................. 4.5 mcg 75% Fluoride (as sodium fluoride) ... 0.25 mg *

Active ingredient for Caries Prophylaxis: Fluoride as Sodium Fluoride.

Other ingredients: Ascorbic acid, butylated hydroxyl toluene, cholecalciferol, citric acid, compressible sugar, DL-alpha Tocopherol, FD&C yellow #6 aluminum lake, folic acid, gelatin, magnesium stearate, maltodextrin, mannitol, medium chain triglycerides, methyl cellulose, mono- and di-glycerides, niacinamide, orange flavor, povidone, pyridoxine, riboflavin, silicon dioxide, sodium ascorbate, sodium citrate, starches, sucralose, thiamine, vitamin A acetate, vitamin B12 and vitamin E acetate.

CLINICAL PHARMACOLOGY

It is well established that fluoridation of the water supply (1 ppm fluoride) during the period of tooth development leads to a significant decrease in the incidence of dental caries.

Multi-vitamin with Fluoride Chewable Tablets provide sodium fluoride and ten essential vitamins in a chewable tablet. Because the tablets are chewable, they provide a topical as well as systemic source of fluoride.

Hydroxyapatite is the principal crystal for all calcified tissue in the human body. The fluoride ion reacts with the hydroxyapatite in the tooth as it is formed to produce the more caries-resistant crystal, fluorapatite. The reaction may be expressed by the equation:

Ca10(PO4)6(OH)2 + 2F-  —————> Ca10(PO4)6F2 + 2OH-

(Hydroxyapatite)                                   (Fluorapatite)

Three stages of fluoride deposition in tooth enamel can be distinguished:

1. Small amounts (reflecting the low levels of fluoride in tissue fluids) are incorporated into the enamel crystals while they are being formed.

2. After enamel has been laid down, fluoride deposition continues in the surface enamel. Diffusion of fluoride from the surface inward is apparently restricted.

3. After eruption, the surface enamel acquires fluoride from the water, food, supplementary fluoride and smaller amounts from saliva.

INDICATIONS AND USAGE

Supplementation of the diet with ten essential vitamins.

Supplementation of the diet with fluoride for caries prophylaxis.

See Dosage and Administration.

Multi-vitamin with Fluoride Chewable Tablets supply significant amounts of Vitamins A, C, D, E, thiamin, riboflavin, niacin, vitamin B6, vitamin B12, and folate to supplement the diet, and to help assure that nutritional deficiencies of these vitamins will not develop. Thus, in a single easy-to-use preparation, children obtain ten essential vitamins and the important mineral, fluoride.

The American Academy of Pediatrics recommends that children up to age 16, in areas where drinking water contains less than optimal levels of fluoride, receive daily fluoride supplementation.

Children using Multi-vitamin with fluoride Chewable Tablets regularly should receive semiannual dental examinations. The regular brushing of teeth and attention to good oral hygiene practices are also essential.

WARNINGS

As in the case of all medications, keep out of the reach of children.

Should be chewed. This product, as all chewable tablets, is not recommended for children under age 4 due to risk of choking.

PRECAUTIONS

The suggested dose of Multi-vitamin with Fluoride Chewable Tablets should not be exceeded, since dental fluorosis may result from continued ingestion of large amounts of fluoride.

Before prescribing Multi-vitamin with Fluoride Chewable Tablets, read these Important Considerations When Using Dosage Schedule found in Dosage and Administration.

If fluoride level is unknown, drinking water should be tested for fluoride content before supplements are prescribed. For testing of fluoride content, contact the local or state health department. All sources of fluoride should be evaluated with a thorough fluoride history. Patient exposure to multiple water sources can make proper prescribing complex. Ingestion of higher than recommended levels of fluoride by children has been associated with an increase in mild dental fluorosis in developing, unerupted teeth. Fluoride supplements require long-term compliance on a daily basis. ADVERSE REACTIONS

Allergic rash and other idiosyncrasies have been rarely reported.

DOSAGE AND ADMINISTRATION *1.0 ppm = 1 mg / liter **2.2 mg Sodium Fluoride contains 1mg fluoride ion. Fluoride Ion Level in Drinking Water (ppm)* AGE <0.3 ppm 0.3-0.6 ppm >0.6 ppm 4-6 years 0.50 mg / day**(2 tablets) 0.25 mg / day(1 tablet) None 6-16 years 1.0 mg / day(4 tablets) 0.50 mg / day(2 tablets) None HOW SUPPLIED

Multi-vitamin 1 mg Sodium Fluoride Tablets: grape flavored, round, purple, debossed “BP 815”, available in 100 ct. bottle, NDC 64376-815-01.

Multi-vitamin 0.5 mg Sodium Fluoride Tablets: cherry flavored, square, red, debossed “BP 814”, available in 100 ct. bottle, NDC 64376-814-01.

Multi-vitamin 0.25 mg Sodium Fluoride Tablets: orange flavored, round, orange, debossed “BP 813”, available in 100 ct. bottle, NDC 64376-813-01.

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C -30°C (59°-86°F) [See USP Controlled Room Temperature].

Manufactured for: Boca Pharmacal, Inc.
Coral Springs, FL 33065 www.bocapharmacal.com

1-800-354-8460 Iss. 08/11

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

[Rev 18]


MULTI-VITAMIN WITH FLUORIDE 
vitamin a, vitamin d, thiamine, riboflavin, niacin, pyridoxine, folic acid, fluoride ion, ascorbic acid, .alpha.-tocopherol-acetate-dl, cyanocobalamin  tablet, chewable Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 64376-813 Route of Administration ORAL DEA Schedule      Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength VITAMIN A (VITAMIN A) VITAMIN A 2500 [iU] VITAMIN D (VITAMIN D) VITAMIN D 400 [iU] THIAMINE (THIAMINE) THIAMINE 1.05 mg RIBOFLAVIN (RIBOFLAVIN) RIBOFLAVIN 1.2 mg NIACIN (NIACIN) NIACIN 13.5 mg PYRIDOXINE (PYRIDOXINE) PYRIDOXINE 1.05 mg FOLIC ACID (FOLIC ACID) FOLIC ACID 0.3 mg FLUORIDE ION (FLUORIDE ION) FLUORIDE ION 0.25 mg ASCORBIC ACID (ASCORBIC ACID) ASCORBIC ACID 60 mg .ALPHA.-TOCOPHEROL ACETATE, DL- (.ALPHA.-TOCOPHEROL ACETATE, DL-) .ALPHA.-TOCOPHEROL ACETATE, DL- 15 [iU] CYANOCOBALAMIN (CYANOCOBALAMIN) CYANOCOBALAMIN 4.5 ug Inactive Ingredients Ingredient Name Strength MALTODEXTRIN   CHOLECALCIFEROL   CYANOCOBALAMIN   FD&C YELLOW NO. 6   FOLIC ACID   GELATIN   MEDIUM-CHAIN TRIGLYCERIDES   MAGNESIUM STEARATE   MANNITOL   NIACINAMIDE   POVIDONE   .ALPHA.-TOCOPHEROL ACETATE   .ALPHA.-TOCOPHEROL, DL-   RIBOFLAVIN   SILICON DIOXIDE   CITRIC ACID MONOHYDRATE   THIAMINE   VITAMIN A ACETATE   ASCORBIC ACID   GLYCERYL MONOSTEARATE   BUTYLATED HYDROXYTOLUENE   SUCROSE   PYRIDOXINE   SODIUM ASCORBATE   SODIUM CITRATE   STARCH, CORN   SUCRALOSE   ORANGE   CELLULOSE, MICROCRYSTALLINE   Product Characteristics Color ORANGE Score no score Shape ROUND (Flat) Size 13mm Flavor ORANGE Imprint Code BP;813 Contains          Packaging # NDC Package Description Multilevel Packaging 1 64376-813-01 100 TABLET In 1 BOTTLE None
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date Unapproved drug other 12/28/2011
Labeler - Boca Pharmacal, Inc (170266089) Registrant - Boca Pharmacal, Inc (170266089) Establishment Name Address ID/FEI Operations Cispharma, Inc 833171445 MANUFACTURE Revised: 01/2012Boca Pharmacal, Inc
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Carnitor 1 g Solution for Injection


1. Name Of The Medicinal Product

Carnitor 1 g Solution for Injection

2. Qualitative And Quantitative Composition

L-carnitine inner salt 1 g

3. Pharmaceutical Form

A clear, colourless or light straw- coloured solution

4. Clinical Particulars 4.1 Therapeutic Indications

Indicated for the treatment of primary and secondary carnitine deficiency in adults, children, infants and neonates.

Secondary carnitine deficiency in haemodialysis patients.

Secondary carnitine deficiency should be suspected in long-term haemodialysis patients who have the following conditions:

1. Severe and persistent muscle cramps and/or hypotensive episodes during dialysis.

2. Lack of energy causing a significant negative effect on the quality of life.

3. Skeletal muscle weakness and/or myopathy.

4. Cardiomyopathy.

5. Anaemia of uraemia unresponsive to or requiring large doses of erythropoietin.

6. Muscle mass loss caused by malnutrition.

4.2 Posology And Method Of Administration

For slow intravenous administration over 2-3 minutes

Adults, Children, infants and neonates

It is advisable to monitor therapy by measuring free and acyl carnitine levels in both plasma and urine.

The management of inborn errors of metabolism:

The dosage required depends upon the specific inborn error of metabolism concerned and the severity of presentation at the time of treatment. However, the following can be considered as a general guide.

In acute decompensation, dosages of up to 100 mg/kg/day in 3-4 divided doses are recommended. Higher doses have been used although an increase in adverse events, primarily diarrhoea, may occur.

Secondary carnitine deficiency in haemodialysis patients:

It is strongly recommended that, before initiating therapy with Carnitor, plasma carnitine is measured. Secondary carnitine deficiency is suggested by a plasma ratio of acyl to free carnitine of greater than 0.4 and/or when free carnitine concentrations are lower than 20 ?mol/litre.

A dose of 20mg per kg should be administered as an intravenous bolus at the end of each dialysis session (assuming three sessions per week). The duration of intravenous treatment should be at least three months, which is the time usually required to restore normal muscle levels of free carnitine. The overall response should be assessed by monitoring plasma acyl to free carnitine levels and by evaluating the patient's symptoms. When carnitine supplementation has been stopped there will be a progressive decline in carnitine levels. The need for a repeat course of therapy can be assessed by plasma carnitine assays at regular intervals and by monitoring the patient's symptoms.

Haemodialysis - maintenance therapy:

If significant clinical benefit has been gained by the first course of intravenous Carnitor then maintenance therapy can be considered using 1 g per day of Carnitor orally. On the day of the dialysis, oral Carnitor has to be administered at the end of the session.

4.3 Contraindications

Hypersensitivity to any of the constituents of the product.

4.4 Special Warnings And Precautions For Use

While improving glucose utilisation, the administration of L-carnitine to diabetic patients receiving either insulin or hypoglycaemic oral treatment may result in hypoglycaemia. Plasma glucose levels in these subjects must be monitored regularly in order to adjust the hypoglycaemic treatment immediately, if required.

The safety and efficacy of oral L-carnitine has not been evaluated in patients with renal insufficiency. Chronic administration of high doses of oral L-carnitine in patients with severely compromised renal function or in end stage renal disease (ESRD) patients on dialysis may result in an accumulation of the potentially toxic metabolites, trimethylamine (TMA) and trimethylamine-N-oxide (TMAO), since these metabolites are usually excreted in the urine. This situation has not been observed following intravenous administration of L-carnitine.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

There are no known interactions.

4.6 Pregnancy And Lactation

Reproductive studies were performed in rats and rabbits. There was no evidence of a teratogenic effect in either species. In the rabbit but not in the rat, there was a statistically insignificant greater number of post implantation losses at the highest dose tested (600 mg/kg daily) as compared with control animals. The significance of these findings for man is unknown. There is no experience of use in pregnant patients with primary systemic carnitine deficiency.

Taking into account the serious consequences to a pregnant woman who has primary systemic carnitine deficiency stopping treatment, the risk to the mother of discontinuing treatment seems greater than the theoretical risk to the foetus if treatment is continued.

Levocarnitine is a normal component of human milk. Use of levocarnitine supplementation in nursing mothers has not been studied.

4.7 Effects On Ability To Drive And Use Machines

None known.

4.8 Undesirable Effects

Various mild gastro-intestinal complaints have been reported during the long-term administration of oral levocarnitine, these include transient nausea and vomiting, abdominal cramps and diarrhoea.

Decreasing the dosage often diminishes or eliminates drug-related patient body odour or gastro-intestinal symptoms when present. Tolerance should be monitored very closely during the first week of administration and after any dosage increase.

4.9 Overdose

There have been no reports of toxicity from levocarnitine overdosage. Overdosage should be treated with supportive care.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

ATC Code: A16AA01 (Amino acids and derivatives)

L-Carnitine is present as a natural constituent in animal tissues, micro-organisms and plants. In man the physiological metabolic requirements are met both by the consumption of food containing carnitine and the endogenous synthesis in the liver and kidneys from lysine with methionine serving as the methyl donor. Only the L-isomer is biologically active, playing an essential role in lipid metabolism as well as in the metabolism of ketone bodies as branched chain-amino-acids. L-Carnitine as a factor is necessary in the transport of long-chain fatty acids into the mitochondria – facilitating the oxidation of fatty acids rather than their incorporation into triglycerides. By releasing CoA from its thioesters, through the action of CoA; carnitine acetyl transferase, L-carnitine also enhances the metabolic flux in the Kreb's cycle; with the same mechanism it stimulates the activity of pyruvate dehydrogenase and in skeletal muscle, the oxidation of branched chain-amino acids. L-Carnitine is thus involved, directly or indirectly in several pathways so that its availability should be an important factor controlling not only the oxidative utilisation of fatty acids and ketone bodies but also that of glucose and some amino acids.

5.2 Pharmacokinetic Properties

The absorbed L-carnitine is transported to various organ systems via the blood. The presence of membrane-bound proteins in several tissues including red blood cells that bind carnitine, suggest that a transport system in the blood and a cellular system for the collective uptake is present in several tissues. Tissue and serum carnitine concentration depends on several metabolic processes, carnitine biosynthesis and dietary contributions, transport into and out of tissues, degradation and excretion may all affect tissue carnitine concentrations.

Absorption

L-Carnitine is absorbed by the mucosal cells of the small intestine and enters the blood stream relatively slowly; the absorption is probably associated with an active transluminal mechanism.

The apparent systemic availability after oral administration is limited (<10%) and variable.

Distribution

Absorbed L-carnitine is transported to various organ systems via the blood; it is thought that a transport system in the blood and a cellular system for selective uptake is involved.

Excretion

L-Carnitine is excreted mainly in the urine and is variable. The excretion is directly proportional to the blood levels.

Metabolism

L-Carnitine is metabolised to a very limited extent.

5.3 Preclinical Safety Data

L-Carnitine is a naturally occurring body substance in human beings, plants and animals. Carnitor products are used to bring the level of L-carnitine in the body up to those found naturally. Appropriate pre-clinical studies have been undertaken and show no signs of toxicity at normal therapeutic doses.

6. Pharmaceutical Particulars 6.1 List Of Excipients

Hydrochloric acid 10%

Water for injection

6.2 Incompatibilities

None known.

6.3 Shelf Life

5 years.

6.4 Special Precautions For Storage

Store below 25oC.

Store in the original carton in order to protect from light.

6.5 Nature And Contents Of Container

Ph.Eur. Type 1 clear glass ampoules of 5 ml capacity.

The ampoules are packed in cardboard outer cartons containing 5 ampoules.

6.6 Special Precautions For Disposal And Other Handling

None.

7. Marketing Authorisation Holder

Sigma-Tau Industrie Farmaceutiche Riunite SpA,

Viale Shakespeare 47-00144,

Rome, Italy.

8. Marketing Authorisation Number(S)

PL 08381/0003

9. Date Of First Authorisation/Renewal Of The Authorisation

30 November 1999

10. Date Of Revision Of The Text

November 2008


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Ismelin ampoules 10mg / ml


1. Name Of The Medicinal Product

Ismelin®ampoules l0mg/ml

2. Qualitative And Quantitative Composition

Guanethidine monosulphate Ph.Eur. 10mg/ml

3. Pharmaceutical Form

A colourless solution in a clear glass l ml ampoule, for intramuscular administration.

4. Clinical Particulars 4.1 Therapeutic Indications

Control of hypertensive crises, and to obtain more rapid blood pressure control.

4.2 Posology And Method Of Administration

Adults:

Ismelin should be given by intramuscular injection. One injection of 10 to 20mg will generally cause a fall in blood pressure within 30 minutes which reaches a maximum in one to two hours and is maintained for four to six hours. If a further dose of 10 to 20mg is deemed necessary, then three hours should be allowed to elapse between doses.

In hypertensive patients with moderate renal insufficiency, the intervals between dosing should be extended or the dosage reduced to avoid accumulation as the drug is renally excreted. (For patients with renal failure, see Section 4.3, "Contra

Children: not recommended.

Elderly: Clinical evidence would indicate that no special dosage regime is necessary, but concurrent coronary or cerebral insufficiency should be taken into account.

4.3 Contraindications

Cases of phaeochromocytoma and patients previously treated with monoamine oxidase inhibitors (see Section 4.5, "Interactions with other medicaments and other forms of interaction"); in such cases, Ismelin may lead to the release of large quantities of catecholamines, which may cause a hypertensive crisis.

Patients with known hypersensitivity to guanethidine and related derivatives. Heart failure due to causes other than hypertension. Renal failure (creatinine clearance 10 to 40ml/min).

4.4 Special Warnings And Precautions For Use

Heat and physical exertion may increase the antihypertensive effect of Ismelin.

Ismelin should be used with caution in patients with moderate renal insufficiency (creatinine clearance 41 to 65ml/min), or with coronary and/or cerebral arteriosclerosis; abrupt lowering of blood pressure should be avoided. Caution should be exercised in asthmatic patients or in patients with a history of gastro

The concurrent administration of guanethidine and ?

When patients have to undergo surgery, it is recommended that treatment with Ismelin be withdrawn a few days before the operation. To avoid excessive bradycardia during anaesthesia, it is advisable to premedicate with larger than usual doses of atropine.

After prolonged treatment with Ismelin, latent heart failure may develop. This is due to salt and water retention, and mild negative inotropic and chronotropic effects. Concomitant administration of diuretics can readily correct this condition.

If patients develop fever, the dose of Ismelin should be lowered.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Monoamine oxidase inhibitors should be withdrawn at least fourteen days before starting treatment with Ismelin (See Section 4.3, "Contra

Concurrent administration of Ismelin with anti

The anti-hypertensive action of Ismelin may be enhanced by other anti-hypertensive agents such as reserpine, methyldopa, vasodilators (especially minoxidil), calcium antagonists, ?

The anti-hypertensive action of Ismelin may be reduced by chlorpromazine, phenothiazine derivatives, tricyclic antidepressants and related anti-psychotic drugs, and oral contraceptives. Consequently if larger doses of Ismelin are prescribed, care must be taken upon the withdrawal of any of the drugs listed, as severe hypotension may ensue if the dose of Ismelin is not adjusted in advance.

After prolonged treatment with Ismelin, it may be necessary to adjust the dosage of insulin or oral anti

Patients on Ismelin may become hypersensitive to adrenaline, amphetamines or other sympathomimetic agents. Therefore caution should be exercised when taking or using preparations containing these drugs.

4.6 Pregnancy And Lactation

No foetal toxicity or fertility studies have been carried out in animals. Therefore the drug should only be used if there is no safer alternative. However, in particular, it should not be used during the first trimester of pregnancy nor within at least two weeks prior to the birth or during labour since it may induce paralytic ileus in the newborn infant.

In mothers receiving Ismelin in therapeutic doses, the active substance passes into the breast milk, but in quantities so small that no undesirable effects on the infant are to be expected.

4.7 Effects On Ability To Drive And Use Machines

Patients should be warned of the potential hazards of driving or operating machinery if they experience side effects such as dizziness, blurred vision or drowsiness.

4.8 Undesirable Effects

Side effects are often an indication of excessive dosage. The following effects may occur:

Central nervous system: Particularly at the start of treatment: dizziness, tiredness, lethargy, paraesthesia and headache. Occasional: blurred vision and depression. Rare: myalgia and muscular tremor.

Cardiovascular system: Postural hypotension (which may be associated with cerebral or myocardial ischaemia in severe cases) especially when getting up in the morning or after physical exertion, sick

Gastro Diarrhoea and gaseous distension. Occasional: vomiting, nausea and dry mouth. Rare: swelling of parotid glands.

Respiratory tract: Nasal congestion. Rare: asthma.

Urogenital system: Raised BUN levels or uraemia in patients with latent or manifest renal failure, and ejaculation disturbances.

Skin and hair: Occasional: dermatitis. Rare: hair loss.

Blood: Isolated reports of anaemia, leucopenia, and/or thrombocytopenia.

4.9 Overdose

Symptoms: may include postural hypotension which may cause syncope, sinus bradycardia (although tachycardia has been observed), tiredness, dizziness, blurring of vision, muscular weakness, nausea, vomiting, severe diarrhoea and oliguria.

Treatment: Postural hypotension may be overcome by keeping the patient recumbent, or by instituting fluid and electrolyte replacement, and if necessary, by cautious administration of pressor agents (see Section 4.5, "Interactions with other medicaments and other forms of interaction"). Sinus bradycardia can be treated with atropine, and diarrhoea with an anticholinergic agent.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

Ismelin is a peripheral sympathetic blocking drug which lowers blood pressure by depleting and inhibiting reformation of noradrenaline in postganglionic nerve endings. Guanethidine, being highly polar, does not cross the blood

5.2 Pharmacokinetic Properties

Guanethidine may be excreted more slowly in those patients with moderate to severely compromised renal function, therefore the potential for accumulation of the drug will be higher.

5.3 Preclinical Safety Data

There are no pre

6. Pharmaceutical Particulars 6.1 List Of Excipients

Sodium chloride, sulphuric acid and water for injections.

6.2 Incompatibilities

None known.

6.3 Shelf Life

5 years.

6.4 Special Precautions For Storage

None.

6.5 Nature And Contents Of Container

Clear glass type I, l ml ampoules containing l0mg/ml: Boxes of 5.

6.6 Special Precautions For Disposal And Other Handling

None

Administrative Data 7. Marketing Authorisation Holder

Amdipharm Plc

Regency House

Miles Gray Road

Basildon

Essex SS14 3AF

United Kingdom

8. Marketing Authorisation Number(S)

PL 20072/0027

9. Date Of First Authorisation/Renewal Of The Authorisation

18th April 2005

10. Date Of Revision Of The Text Legal Status

POM


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Liposic


1. Name Of The Medicinal Product

Liposic®, eye gel

2. Qualitative And Quantitative Composition

Each 1g of gel contains 2mg of carbomer

For excipients see 6.1

3. Pharmaceutical Form

Eye gel; white, turbid, highly viscous, dripable

4. Clinical Particulars 4.1 Therapeutic Indications

Symptomatic treatment of dry eye syndrome

4.2 Posology And Method Of Administration

Therapy of dry eye conditions requires an individual dosage regimen.

According to the severity and intensity of the symptoms, instill one drop into the conjunctival sac 3

Generally, an ophthalmologist should be consulted when treating keratoconjunctivitis sicca, which normally turns out to be long-term or permanent therapy.

An appropriate drop size is obtained when the tube is held in a vertical position above the eye during instillation.

4.3 Contraindications

Hypersensitivity to any component of this product

4.4 Special Warnings And Precautions For Use

Contact lenses should be removed prior to administration, and may be inserted again 30 minutes after Liposic has been instilled. Concomitant ocular medication should be administered 15 minutes prior to instillation of Liposic (see 4.5).

No specific studies with Liposic have been performed in children.

If the symptoms of the dry eye continue or worsen, treatment should be stopped and an ophthalmologist should be consulted.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

None known

Please note:

Liposic may prolong the contact-time of topically applied drugs in ophthalmology. Concomitant ocular medication should be administered 15 minutes prior to instillation of Liposic.

4.6 Pregnancy And Lactation

Clinical data regarding the safety of Liposic in human pregnancy or lactation are not available. Preclinical data predict that the risk of Liposic use in human pregnancy or lactation is very low. But due to the lack of clinical data the use of Liposic during pregnancy or lactation can not be recommended.

4.7 Effects On Ability To Drive And Use Machines

Even when used as indicated, this medicinal product may impair visual acuity for about five minutes due to the formation of streaks after gel application, and patients should exercise caution when driving vehicles or operating machinery.

4.8 Undesirable Effects

Ocular irritation may occur in rare cases due to the preservative contained. Intolerance reactions to one of the ingredients may be seen in isolated cases. Observed undesirable effects include burning, reddening of the eyes, sticky eyelids, palpebral giant papillary conjunctivitis, corneal stipples, episcleritis, blurred vision, itching, discomfort

4.9 Overdose

Any ocular overdosage or oral intake which might occur is of no clinical relevance. However, care should be taken to administer small drops to the eye to avoid sticky eyelids.

5. Pharmacological Properties

ATC code S01XA20

5.1 Pharmacodynamic Properties

Liposic eye gel is based on a high molecular weight hydrophilic polymer. Its pH and osmolality are similar to those of the normal tear film. Due to its physical properties, the eye gel binds water and forms a translucent lubricating and wetting film on the surface of the eye. The gel structure is destroyed by the salts contained in the lacrimal fluid and releases moisture. A study in 54 patients with keratoconjunctivitis sicca found that Liposic therapy prolonged tear break-up time from a mean of 5.3 seconds to 11.2 seconds after 6 weeks. Schirmer I-test values were increased from a mean of 4.8 mm to 10.7 mm after 6 weeks.

5.2 Pharmacokinetic Properties

No controlled animal nor human pharmacokinetic studies with this product are available. However, absorption or accumulation in eye tissues can presumably be excluded due to the high molecular weight of carbomer. Clinical studies performed with an essentially similar product have shown that ocular residence time can be assumed to be approximately up to 90 minutes.

5.3 Preclinical Safety Data

Preclinical data reveal no special hazard for humans based on studies of repeated dose toxicity, genotoxicity, carcinogenic potential, reproductive toxicity and pharmacological safety.

6. Pharmaceutical Particulars 6.1 List Of Excipients

Cetrimide, sorbitol, medium-chain triglycerides, sodium hydroxide (for pH adjustment), purified water

6.2 Incompatibilities

None known so far.

6.3 Shelf Life

3 years

28 days after opening of the container

6.4 Special Precautions For Storage

Do not store above 25?C

6.5 Nature And Contents Of Container

Tubes of 5 g eye gel. Packs with one or three tubes of 5 g eye gel.

Tubes of 10 g eye gel. Packs with one or three tubes of 10 g eye gel.

6.6 Special Precautions For Disposal And Other Handling

No special requirements

7. Marketing Authorisation Holder

Dr. Gerhard Mann

Chem.-Pharm. Fabrik GmbH

Brunsbuetteler Damm 165-173

13581 Berlin (Germany)

8. Marketing Authorisation Number(S)

PL 13757/0001

9. Date Of First Authorisation/Renewal Of The Authorisation

21 March 2000

10. Date Of Revision Of The Text

26 October 2001

11. Legal Category

P


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Betadine Alcoholic Solution (Molnlycke Health Care )


1. Name Of The Medicinal Product

Betadine Alcoholic Solution.

2. Qualitative And Quantitative Composition

Povidone iodine 10.0% w/v.

3. Pharmaceutical Form

Alcoholic solution.

4. Clinical Particulars 4.1 Therapeutic Indications

For use as an antiseptic skin cleanser for major and minor surgical procedures where a quick drying effect is desired.

4.2 Posology And Method Of Administration

For topical administration.

4.3 Contraindications

Known or suspected iodine hypersensitivity. Regular use is contraindicated in patients and users with thyroid disorders (in particular nodular colloid goitre, endemic goitre and Hashimoto's thyroiditis).

4.4 Special Warnings And Precautions For Use

Special caution is needed when regular applications to broken skin are made to patients with pre-existing renal insufficiency.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Absorption of iodine from povidone iodine through either intact or damaged skin may interfere with thyroid function tests. Contamination with povidone iodine of several types of tests for the detection of occult blood in faeces or blood in urine may produce false-positive results.

4.6 Pregnancy And Lactation

Regular use of povidone iodine should be avoided in pregnant or lactating women as absorbed iodine can cross the placental barrier and can be secreted into breast milk. Although no adverse effects have been reported from limited use, caution should be recommended and therapeutic benefit must be balanced against possible effects of the absorption of iodine on foetal thyroid function and development.

4.7 Effects On Ability To Drive And Use Machines

None known.

4.8 Undesirable Effects

Povidone iodine may produce local skin reactions, although it is considered to be less irritant than iodine. The application of povidone iodine to large wounds or severe burns may produce systemic adverse effects such as metabolic acidosis, hypernatraemia and impairment of renal function.

4.9 Overdose

Excess iodine can produce goitre and hypothyroidism or hyperthyroidism. Systemic absorption of iodine after repeated application of povidone iodine to large areas of wounds or burns may lead to a number of adverse effects: metallic taste in mouth, increased salivation, burning or pain in the throat or mouth, irritation and swelling of the eyes, pulmonary oedema, skin reactions, gastrointestinal upset and diarrhoea, metabolic acidosis, hypernatraemia and renal impairment. Treatment: In the case of accidental ingestion of large quantities of Betadine symptomatic and supportive treatment should be provided, with special attention to electrolyte balance and renal and thyroid function.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

The active ingredient, povidone iodine, slowly liberates iodine when in contact with skin and mucous membranes. The activity of 'iodine' as a microbicide is then governed by a series of dissociations: I2? I+ + I- ; I2 + H2O ? H2O I+ + I- ; I2 + I- ? I3-. The microbicidal species H2O I+ preferentially displaces oxygen as the end electron acceptor in the microorganism's respiratory cycle. H2O I+ similarly interacts within the electron transport chain and reacts with the amino acids of the microbial cell membrane.

5.2 Pharmacokinetic Properties

Betadine Alcoholic Solution is for topical application and therefore a consideration of the absorption, distribution, metabolism and excretion of povidone iodine is largely without relevance.

5.3 Preclinical Safety Data

Not applicable.

6. Pharmaceutical Particulars 6.1 List Of Excipients

Nonoxynol 9; dibasic sodium phosphate (anhydrous); citric acid monohydrate; glycerol; industrial methylated spirit; sodium hydroxide; purified water.

6.2 Incompatibilities

None.

6.3 Shelf Life

36 months.

6.4 Special Precautions For Storage

To be stored at or below 25 degrees Celsius and protected from light.

6.5 Nature And Contents Of Container

High-density polyethylene containers fitted with steran lined white polypropylene caps. Pack size: 500ml

6.6 Special Precautions For Disposal And Other Handling

None stated.

7. Marketing Authorisation Holder

Medlock Medical Limited, Tubiton House, Medlock Street, Oldham, OL1 3HS.

8. Marketing Authorisation Number(S)

PL 21248/0002.

9. Date Of First Authorisation/Renewal Of The Authorisation

14th March 2005.

10. Date Of Revision Of The Text

March 2005.


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Azelex


azelaic acid
Dosage Form: cream
Azelex®
(azelaic acid cream) 20%

For Dermatologic Use Only
Not for Ophthalmic Use

DESCRIPTION

Azelex® (azelaic acid cream) 20% contains azelaic acid, a naturally occurring saturated dicarboxylic acid.

Structural Formula: HOOC-(CH2)7-COOH

Chemical Name: 1,7-heptanedicarboxylic acid

Empirical Formula: C9H16O4

Molecular Weight: 188.22

Active Ingredient: Each gram of Azelex® contains azelaic acid......... 0.2 gm (20% w/w).

Inactive Ingredients: cetearyl octanoate; glycerin; glyceryl stearate and cetearyl alcohol and cetyl palmitate and cocoglycerides; PEG-5 glyceryl stearate; propylene glycol; and purified water. Benzoic acid is present as a preservative.

CLINICAL PHARMACOLOGY

The exact mechanism of action of azelaic acid is not known. The following in vitro data are available, but their clinical significance is unknown. Azelaic acid has been shown to possess antimicrobial activity against Propionibacterium acnes and Staphylococcus epidermidis. The antimicrobial action may be attributable to inhibition of microbial cellular protein synthesis.

A normalization of keratinization leading to an anticomedonal effect of azelaic acid may also contribute to its clinical activity. Electron microscopic and immunohistochemical evaluation of skin biopsies from human subjects treated with Azelex® Cream demonstrated a reduction in the thickness of the stratum corneum, a reduction in number and size of keratohyalin granules, and a reduction in the amount and distribution of filaggrin (a protein component of keratohyalin) in epidermal layers. This is suggestive of the ability to decrease microcomedo formation.

Pharmacokinetics: Following a single application of Azelex® Cream to human skin in vitro, azelaic acid penetrates into the stratum corneum (approximately 3 to 5% of the applied dose) and other viable skin layers (up to 10% of the dose is found in the epidermis and dermis). Negligible cutaneous metabolism occurs after topical application. Approximately 4% of the topically applied azelaic acid is systemically absorbed. Azelaic acid is mainly excreted unchanged in the urine but undergoes some ?-oxidation to shorter chain dicarboxylic acids. The observed half-lives in healthy subjects are approximately 45 minutes after oral dosing and 12 hours after topical dosing, indicating percutaneous absorption rate-limited kinetics.

Azelaic acid is a dietary constituent (whole grain cereals and animal products), and can be formed endogenously from longer-chain dicarboxylic acids, metabolism of oleic acid, and ?-oxidation of monocarboxylic acids. Endogenous plasma concentration (20 to 80 ng/mL) and daily urinary excretion (4 to 28 mg) of azelaic acid are highly dependent on dietary intake. After topical treatment with Azelex® Cream in humans, plasma concentration and urinary excretion of azelaic acid are not significantly different from baseline levels.

INDICATIONS AND USAGE

Azelex® Cream is indicated for the topical treatment of mild-to-moderate inflammatory acne vulgaris.

CONTRAINDICATIONS

Azelex® Cream is contraindicated in individuals who have shown hypersensitivity to any of its components.

WARNINGS

Azelex® Cream is for dermatologic use only and not for ophthalmic use.

There have been isolated reports of hypopigmentation after use of azelaic acid. Since azelaic acid has not been well studied in patients with dark complexions, these patients should be monitored for early signs of hypopigmentation.

PRECAUTIONS General:

If sensitivity or severe irritation develop with the use of Azelex® Cream, treatment should be discontinued and appropriate therapy instituted.

Information for patients:

Patients should be told:

To use Azelex® Cream for the full prescribed treatment period. To avoid the use of occlusive dressings or wrappings. To keep Azelex® Cream away from the mouth, eyes and other mucous membranes. If it does come in contact with the eyes, they should wash their eyes with large amounts of water and consult a physician if eye irritation persists. If they have dark complexions, to report abnormal changes in skin color to their physician. Due in part to the low pH of azelaic acid, temporary skin irritation (pruritus, burning, or stinging) may occur when Azelex® Cream is applied to broken or inflamed skin, usually at the start of treatment. However, this irritation commonly subsides if treatment is continued. If it continues, Azelex® Cream should be applied only once-a-day, or the treatment should be stopped until these effects have subsided. If troublesome irritation persists, use should be discontinued, and patients should consult their physician. (See ADVERSE REACTIONS.) Carcinogenesis, mutagenesis, impairment of fertility:

Azelaic acid is a human dietary component of a simple molecular structure that does not suggest carcinogenic potential, and it does not belong to a class of drugs for which there is a concern about carcinogenicity. Therefore, animal studies to evaluate carcinogenic potential with Azelex® Cream were not deemed necessary. In a battery of tests (Ames assay, HGPRT test in Chinese hamster ovary cells, human lymphocyte test, dominant lethal assay in mice), azelaic acid was found to be nonmutagenic. Animal studies have shown no adverse effects on fertility.

Pregnancy: Teratogenic Effects: Pregnancy Category B.

Embryotoxic effects were observed in Segment I and Segment II oral studies with rats receiving 2500 mg/kg/day of azelaic acid. Similar effects were observed in Segment II studies in rabbits given 150 to 500 mg/kg/day and in monkeys given 500 mg/kg/day. The doses at which these effects were noted were all within toxic dose ranges for the dams. No teratogenic effects were observed. 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 be used during pregnancy only if clearly needed.

Nursing Mothers:

Equilibrium dialysis was used to assess human milk partitioning in vitro. At an azelaic acid concentration of 25 ?g/mL, the milk/plasma distribution coefficient was 0.7 and the milk/buffer distribution was 1.0, indicating that passage of drug into maternal milk may occur. Since less than 4% of a topically applied dose is systemically absorbed, the uptake of azelaic acid into maternal milk is not expected to cause a significant change from baseline azelaic acid levels in the milk. However, caution should be exercised when Azelex® Cream is administered to a nursing mother.

Pediatric Use:

Safety and effectiveness in pediatric patients under 12 years of age have not been established.

Geriatric Use:

Clinical studies of Azelex® Cream did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

Adverse Reactions

During U.S. clinical trials with Azelex®Cream, adverse reactions were generally mild and transient in nature. The most common adverse reactions occurring in approximately 1-5% of patients were pruritus, burning, stinging and tingling. Other adverse reactions such as erythema, dryness, rash, peeling, irritation, dermatitis, and contact dermatitis were reported in less than 1% of subjects. There is the potential for experiencing allergic reactions with use of Azelex®Cream.

In patients using azelaic acid formulations, the following additional adverse experiences have been reported rarely: worsening of asthma, vitiligo depigmentation, small depigmented spots, hypertrichosis, reddening (signs of keratosis pilaris), and exacerbation of recurrent herpes labialis.

DOSAGE AND ADMINISTRATION

After the skin is thoroughly washed and patted dry, a thin film of Azelex® Cream should be gently but thoroughly massaged into the affected areas twice daily, in the morning and evening. The hands should be washed following application. The duration of use of Azelex® Cream can vary from person to person and depends on the severity of the acne. Improvement of the condition occurs in the majority of patients with inflammatory lesions within four weeks.

HOW SUPPLIED

Azelex® Cream is supplied in a closed orifice tube with a white, spiked screwcap in the following sizes:

30 g - NDC 0023-8694-30
50 g - NDC 0023-8694-50

Note: Protect from freezing. Store product on its side.

Store between 15° - 30° C (59° - 86° F).

Rx Only.

Distributed by:

Irvine, California 92612, U.S.A.

©2004 Allergan, Inc.

Made in Italy

8466X

Distributed under license.

® Mark of Allergan, Inc.

Revised May 2004

70896US15P

NDC 0023-8694-50

ALLERGAN®

Azelex®

(azelaic acid cream) 20%

For Dermatologic Use Only

Not for Ophthalmic Use

Rx Only          50 grams

NDC 0023-8694-50

ALLERGAN®

Azelex®

(azelaic acid cream) 20%

For Dermatologic Use Only

Not for Ophthalmic Use          50 grams

Rx Only


Azelex 
azelaic acid  cream Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0023-8694 Route of Administration CUTANEOUS DEA Schedule      Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength azelaic acid (azelaic acid) azelaic acid 0.2 g  in 1 g Inactive Ingredients Ingredient Name Strength cetearyl ethylhexanoate   glycerin   cetostearyl alcohol   cetyl palmitate   propylene glycol   water   glyceryl monostearate   coco-glycerides   glyceryl monostearate   benzoic acid   Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains          Packaging # NDC Package Description Multilevel Packaging 1 0023-8694-30 1 TUBE In 1 CARTON contains a TUBE 1 30 g In 1 TUBE This package is contained within the CARTON (0023-8694-30) 2 0023-8694-50 1 TUBE In 1 CARTON contains a TUBE 2 50 g In 1 TUBE This package is contained within the CARTON (0023-8694-50)
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA020428 03/21/1996
Labeler - Allergan, Inc. (144796497) Establishment Name Address ID/FEI Operations Intendis Manufacturing SPA 564725468 MANUFACTURE Revised: 01/2011Allergan, Inc. More Azelex resources Azelex Side Effects (in more detail) Azelex Dosage Azelex Use in Pregnancy & Breastfeeding Azelex Drug Interactions Azelex Support Group 2 Reviews for Azelex - Add your own review/rating Azelex Cream MedFacts Consumer Leaflet (Wolters Kluwer) Azelex Topical Advanced Consumer (Micromedex) - Includes Dosage Information Finacea Gel MedFacts Consumer Leaflet (Wolters Kluwer) Finacea Consumer Overview Finacea Plus Gel MedFacts Consumer Leaflet (Wolters Kluwer) Compare Azelex with other medications Acne Rosacea
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Betadine Surgical Scrub (Molnlycke Health Care )


1. Name Of The Medicinal Product

Betadine Surgical Scrub.

2. Qualitative And Quantitative Composition

Povidone Iodine 7.5% w/v.

3. Pharmaceutical Form

Surgical scrub.

4. Clinical Particulars 4.1 Therapeutic Indications

For use as an antiseptic cleanser for pre-operative scrubbing and washing by surgeons and theatre staff, and pre-operative preparation of patients' skin.

4.2 Posology And Method Of Administration

For topical administration. Adults, the elderly and children: Apply full strength as a pre-operative antiseptic skin cleanser. Povidone iodine is not recommended for regular use in neonates and is contraindicated in very low birth weight infants (below 1500 grams).

4.3 Contraindications

Known or suspected iodine hypersensitivity. Regular use is contraindicated in patients and users with thyroid disorders (in particular nodular colloid goitre, endemic goitre and Hashimoto's thyroiditis).

4.4 Special Warnings And Precautions For Use

Special caution is needed when regular applications to broken skin are made to patients with pre-existing renal insufficiency. Regular use should be avoided in patients on concurrent lithium therapy.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Absorption of iodine from povidone iodine through either intact or damaged skin may interfere with thyroid function tests. Contamination with povidone iodine of several types of tests for the detection of occult blood in faeces or blood in urine may produce false-positive results.

4.6 Pregnancy And Lactation

Regular use of povidone iodine should be avoided in pregnant or lactating women as absorbed iodine can cross the placental barrier and can be secreted into breast milk. Although no adverse effects have been reported from limited use, caution should be recommended and therapeutic benefit must be balanced against possible effects of the absorption on foetal thyroid function and development.

4.7 Effects On Ability To Drive And Use Machines

None known.

4.8 Undesirable Effects

Povidone iodine may produce local skin reactions although it is considered to be less irritant than iodine. The application of povidone iodine to large wounds or severe burns may produce systemic adverse effects such as metabolic acidosis, hypernatraemia and impairment of renal function.

4.9 Overdose

Excess iodine can produce goitre and hypothyroidism or hyperthyroidism. Systemic absorption of iodine after repeated application of povidone iodine to large areas of wounds or burns may lead to a number of adverse effects: metallic taste in mouth, irritation and swelling of the eyes, pulmonary oedema, skin reactions, gastrointestinal upset and diarrhoea, metabolic acidosis, hypernatraemia and impairment of renal function. In the case of accidental ingestion of large quantities of Betadine, symptomatic and supportive treatment should be provided with special attention to electrolyte balance and renal and thyroid function.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

The active ingredient, povidone iodine, slowly liberates iodine when in contact with skin and mucous membranes. The activity of 'iodine' as a microbicide is then governed by a series of dissociations: I2? I+ + I- ; I2 + H2O ? H2O I+ + I- ; I2 + I- ? I3-. The microbicidal species H2O I+ preferentially displaces oxygen as the end electron acceptor in the microorganism's respiratory cycle. H2O I+ similarly interacts within the electron transport chain and reacts with the amino acids of the microbial cell membrane.

5.2 Pharmacokinetic Properties

Betadine Surgical Scrub is intended for topical application and therefore a consideration of the absorption, distribution, metabolism and elimination of povidone iodine is largely without relevance.

5.3 Preclinical Safety Data

None stated.

6. Pharmaceutical Particulars 6.1 List Of Excipients

Sulphated nonylphenoxypoly(oxyethylene) ethanol ammonium salt; lauric diethanolamide;

ethoxylated lanolin 50%; Natrosol HXR; sodium hydroxide; purified water.

6.2 Incompatibilities

None stated.

6.3 Shelf Life

36 months unopened.

6.4 Special Precautions For Storage

Store below 25oC and protect from light.

6.5 Nature And Contents Of Container

High density polyethylene containers fitted with steran lined white polypropylene caps containing 500ml of product.

6.6 Special Precautions For Disposal And Other Handling

None stated.

7. Marketing Authorisation Holder

Medlock Medical Limited, Tubiton House, Medlock Street, Oldham, OL1 3HS.

8. Marketing Authorisation Number(S)

PL 21248/0009.

9. Date Of First Authorisation/Renewal Of The Authorisation

6th April 2005.

10. Date Of Revision Of The Text

April 2006.


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Gynoxin 200 mg vaginal capsules


1. Name Of The Medicinal Product

Gynoxin 200 mg Vaginal Capsules

2. Qualitative And Quantitative Composition

Each vaginal capsule contains 200 mg of the active ingredient fenticonazole nitrate.

For excipients, see 6.1

3. Pharmaceutical Form

Vaginal capsule, soft

Ivory white, opaque, soft gelatin capsules

4. Clinical Particulars 4.1 Therapeutic Indications

Treatment of vulvovaginal candidiasis.

4.2 Posology And Method Of Administration

Route of Administration:

Intravaginal

Adults:

One 200 mg vaginal capsule at bedtime for 3 days

The capsule must be introduced deeply into the vagina.

Gynoxin is not greasy, does not soil and can easily be removed with water.

Children:

The use of Gynoxin in children is not recommended.

4.3 Contraindications

Ascertained hypersensitive to the product and to other imidazole derivatives.

4.4 Special Warnings And Precautions For Use

The product should not be used in conjunction with barrier contraceptives.

In the event of a hypersensitivity reaction or development of resistant organisms, treatment should be discontinued and the physician consulted.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Not investigated. Since systemic absorption of fenticonazole after application is low, interactions with other drugs are unlikely.

4.6 Pregnancy And Lactation

Oral administration of fenticonazole in rats has been reported to produce prolonged gestation and embryotoxic effects after doses above 40mg/kg/day. Fenticonazole does not interfere with the function of male and female gonads and does not modify the first phases of reproduction.

Fenticonazole has shown no teratogenic effects in rats and rabbits. Fenticonazole or its metabolites cross the placental barrier in pregnant rats and rabbits after vaginal application and are excreted in milk of lactating rats.

Since there is no experience of use during pregnancy or lactation, Gynoxin should not be used unless the physician considers it essential to the welfare of the patient.

4.7 Effects On Ability To Drive And Use Machines

None.

4.8 Undesirable Effects

After intravaginal administration slight transient burning, which usually disappears rapidly, may occasionally occur.

Prolonged topical application may cause sensitisation reactions.

4.9 Overdose

Because of the low systemic absorption after vaginal application, overdosage is unlikely. In case of a suspected accidental oral ingestion emesis should be induced or gastric lavage may be attempted. Irrespective of success in inducing emesis the patient should be made to drink water or lemonade with active charcoal and a laxative. Symptomatic therapy may be administered if indicated.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

ATC code: G01A F12

Fenticonazole is a broad-spectrum antimycotic agent.

• In vitro: high fungistatic and fungicidal activity against Candida albicans

• In vivo: healing of vaginal mycoses due to Candida within 5 days in mice.

5.2 Pharmacokinetic Properties

Pharmacokinetic studies in humans have shown that systemic absorption of fenticonazole nitrate after vaginal administration is minimal.

5.3 Preclinical Safety Data

LD50 mice: oral>3000mg/kg; i.p 1276mg/kg (M), 1265mg/kg (F)

LD50 rats: oral>3000mg/kg; s.c>750mg/kg; i.p. 440mg/kg (M), 309mg/kg (F)

Chronic toxicity: following oral administration of 40-80-160mg/kg/day for 6 months in rats and dogs, fenticonazole was well tolerated, although some evidence of light and moderate general toxicity occurred (increase in liver weight at 160mg/kg without histopathological alterations in rats, and a transient increase in serum SGPT at 80 and 160mg/kg, together with an increase in liver weight in dogs).

Fenticonazole does not interfere with the function of male and female gonads, and does not modify the first phases of reproduction. Studies in reproductive toxicology revealed, as for other imidazole derivatives, an embryolethal effect at high dosages (>20mg/kg). Fenticonazole has shown no teratogenic effects in rats and rabbits and has revealed no mutagenic potential in six mutagenicity tests.

Satisfactory results were obtained in tolerability tests performed in guinea pigs, rabbits as well as in mini-pigs, the skin of which is similar to that of humans, as far as morphology, functionality and sensitivity to irritating agents are concerned.

Fenticonazole has shown no evidence of sensitisation, phototoxicity and photoallergy.

Pharmacokinetic studies have revealed no transcutaneous absorption either in man or in animals and a very low vaginal absorption.

6. Pharmaceutical Particulars 6.1 List Of Excipients

Medium chain triglycerides

Colloidal anhydrous silica

Shell constituents:

Gelatin

Glycerol

Titanium dioxide

Ethyl parahydroxybenzoate sodium (E215)

Sodium propyl parahydroxybenzoate (E217)

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

3 years

6.4 Special Precautions For Storage

Do not store above 30°C. Do not refrigerate or freeze. Store in the original package.

6.5 Nature And Contents Of Container

Blister pack of PVC/PVdC + aluminium foil, in packs of 3.

6.6 Special Precautions For Disposal And Other Handling

None

Administrative Data 7. Marketing Authorisation Holder

Recordati Industria Chimica e Farmaceutica SpA

Via Matteo Civitali

1-20148 Milano

Italy

8. Marketing Authorisation Number(S)

PL 04595/0007

9. Date Of First Authorisation/Renewal Of The Authorisation

22/09/99

10. Date Of Revision Of The Text

14/12/2009

POM


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Nitrolingual Pump Spray


1. Name Of The Medicinal Product

Nitrolingual Pumpspray

2. Qualitative And Quantitative Composition

Each metered dose contains 400 micrograms glyceryl trinitrate.

3. Pharmaceutical Form

Sublingual spray.

4. Clinical Particulars 4.1 Therapeutic Indications

For the treatment and prophylaxis of angina pectoris and the treatment of variant angina.

4.2 Posology And Method Of Administration

Adults and the Elderly:

At the onset of an attack or prior to a precipitating event: one or two 400 microgram metered doses sprayed under the tongue. It is recommended that no more than three metered-doses are taken at any one time and that there should be a minimum interval of 15 minutes between consecutive treatments.

For the prevention of exercise induced angina or in other precipitating conditions: one or two 400 microgram metered doses sprayed under the tongue immediately prior to the event.

Children:

Nitrolingual Pumpspray is not recommended for use.

Administration:

The bottle should be held vertically with the valve head uppermost. If the pump is new, or has not been used for a week or more, the first actuation should be released into the air. The spray orifice should then be placed as close to the mouth as possible. The dose should be sprayed under the tongue and the mouth should be closed immediately after each dose. The spray should not be inhaled. Patients should be instructed to familiarise themselves with the position of the spray orifice, which can be identified by the finger rest on the top of the valve, in order to facilitate orientation for administration at night. During application the patient should rest, ideally in the sitting position.

4.3 Contraindications

Hypersensitivity to nitrates or any constituent of the formulation. Hypotension, hypovolaemia, severe anaemia, cerebral haemorrhage and brain trauma, mitral stenosis and angina caused by hypertrophic obstructive cardiomyopathy. Concomitant administration of phosphodiesterase inhibitors used for the treatment of erectile dysfunction (section 4.5).

4.4 Special Warnings And Precautions For Use

Any lack of effect may be an indicator of early myocardial infarction.

As with all glyceryl trinitrate preparations, use in patients with incipient glaucoma should be avoided.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Tolerance to this drug and cross tolerance to other nitrates may occur. Alcohol may potentiate any hypotensive effect.

The hypotensive effects of nitrates are potentiated by concurrent administration of phosphodiesterase inhibitors used for the treatment of erectile dysfunction. A severe and possibly dangerous fall in blood pressure may occur. This can result in collapse, unconsciousness and paradoxical myocardial ischaemia and may be fatal. Such use is therefore contra-indicated (section 4.3)

If a patient treated with these drugs for erectile dysfunction needs a rapidly effective nitrate, he/she should be closely monitored.

4.6 Pregnancy And Lactation

Nitrolingual Pump spray is not generally recommended and should be used only if its potential benefit justifies any potential risk to the foetus or neonate.

4.7 Effects On Ability To Drive And Use Machines

Only as a result of hypotension.

4.8 Undesirable Effects

Headache, dizziness, postural hypotension, flushing, tachycardia and paradoxical bradycardia have been reported.

4.9 Overdose

Signs and symptoms:

Flushing, severe headache, a feeling of suffocation, hypotension, fainting, restlessness, blurred vision, impairment of respiration, bradycardia and rarely, cyanosis and methaemoglobinaemia may occur. In a few patients there may be a reaction comparable to shock with nausea, vomiting, weakness, sweating and syncope.

Treatment:

Recovery often occurs without special treatment. Hypotension may be corrected by elevation of the legs to promote venous return. Methaemoglobinaemia should be treated by intravenous methylene blue.

Symptomatic treatment should be given for respiratory and circulatory defects in more serious cases.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

Glyceryl trinitrate relieves angina pectoris by reduction of cardiac work and dilation of the coronary arteries. In this way, not only is there a lessening in arterial oxygen requirement but the amount of oxygenated blood reaching the ischaemic heart is increased.

5.2 Pharmacokinetic Properties

The pharmacokinetics of glyceryl trinitrate are complex; venous plasma levels of the drug show wide and variable fluctuations and are not predictive of clinical effect. In a human pharmacodynamic study, pharmacological activity had commenced one minute after dosing and was obvious by two minutes.

5.3 Preclinical Safety Data

None stated.

6. Pharmaceutical Particulars 6.1 List Of Excipients

Fractionated coconut oil, ethanol (absolute), medium chain partial glycerides, peppermint oil.

6.2 Incompatibilities

Not known.

6.3 Shelf Life

3 years.

6.4 Special Precautions For Storage

Do not store above 25°C.

6.5 Nature And Contents Of Container

Red plastic coated glass bottle fitted with metering pump. Each bottle contains 4.9, 11.2 or 14.2g solution (equivalent to about 75, 200 or 250 doses). Nitrolingual Pumpspray Duo pack contains a 4.9g and a 14.2g bottle.

6.6 Special Precautions For Disposal And Other Handling

See 'Administration' section.

7. Marketing Authorisation Holder

Merck Serono Ltd

Bedfont Cross

Stanwell Road

Feltham

Middlesex

TW14 8NX

UK

8. Marketing Authorisation Number(S)

PL 11648/0082

9. Date Of First Authorisation/Renewal Of The Authorisation

28 November 2005

10. Date Of Revision Of The Text

22nd January 2010

LEGAL CATEGORY Pharmacy


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Casodex 50 mg Film-coated Tablets


1. Name Of The Medicinal Product

Casodex 50 mg Film-coated Tablets

2. Qualitative And Quantitative Composition

Each tablet contains 50 mg bicalutamide (INN)

3. Pharmaceutical Form

White film-coated tablet.

4. Clinical Particulars 4.1 Therapeutic Indications

Treatment of advanced prostate cancer in combination with LHRH analogue therapy or surgical castration.

4.2 Posology And Method Of Administration

Adult males including the elderly: one tablet (50 mg) once a day.

Treatment with Casodex should be started at least 3 days before commencing treatment with an LHRH analogue, or at the same time as surgical castration.

Children: Casodex is contraindicated in children.

Renal impairment: no dosage adjustment is necessary for patients with renal impairment.

Hepatic impairment: no dosage adjustment is necessary for patients with mild hepatic impairment. Increased accumulation may occur in patients with moderate to severe hepatic impairment (see section 4.4).

4.3 Contraindications

Casodex is contraindicated in females and children (see section 4.6).

Casodex must not be given to any patient who has shown a hypersensitivity reaction to the active substance or to any of the excipients of this product.

Co-administration of terfenadine, astemizole or cisapride with Casodex is contraindicated (see section 4.5).

4.4 Special Warnings And Precautions For Use

Initiation of treatment should be under the direct supervision of a specialist.

Casodex is extensively metabolised in the liver. Data suggests that its elimination may be slower in subjects with severe hepatic impairment and this could lead to increased accumulation of Casodex. Therefore, Casodex should be used with caution in patients with moderate to severe hepatic impairment.

Periodic liver function testing should be considered due to the possibility of hepatic changes. The majority of changes are expected to occur within the first 6 months of Casodex therapy.

Severe hepatic changes and hepatic failure have been observed rarely with Casodex, and fatal outcomes have been reported (see section 4.8). Casodex therapy should be discontinued if changes are severe.

A reduction in glucose tolerance has been observed in males receiving LHRH agonists. This may manifest as diabetes or loss of glycaemic control in those with pre-existing diabetes. Consideration should therefore be given to monitoring blood glucose in patients receiving Casodex in combination with LHRH agonists.

Casodex has been shown to inhibit cytochrome P450 (CYP 3A4), as such caution should be exercised when co-administered with drugs metabolised predominantly by CYP 3A4 (see sections 4.3 and 4.5).

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

There is no evidence of any pharmacodynamic or pharmacokinetic interactions between Casodex and LHRH analogues.

In vitro studies have shown that R-bicalutamide is an inhibitor of CYP 3A4, with lesser inhibitory effects on CYP 2C9, 2C19 and 2D6 activity.

Although clinical studies using antipyrine as a marker of cytochrome P450 (CYP) activity showed no evidence of a drug interaction potential with Casodex, mean midazolam exposure (AUC) was increased by up to 80%, after co-administration of Casodex for 28 days. For drugs with a narrow therapeutic index such an increase could be of relevance. As such, concomitant use of terfenadine, astemizole and cisapride is contraindicated (see section 4.3) and caution should be exercised with the co-administration of Casodex with compounds such as ciclosporin and calcium channel blockers. Dosage reduction may be required for these drugs particularly if there is evidence of enhanced or adverse drug effect. For ciclosporin, it is recommended that plasma concentrations and clinical condition are closely monitored following initiation or cessation of Casodex therapy.

Caution should be exercised when prescribing Casodex with other drugs which may inhibit drug oxidation e.g. cimetidine and ketoconazole. In theory, this could result in increased plasma concentrations of Casodex which theoretically could lead to an increase in side effects.

In vitro studies have shown that Casodex can displace the coumarin anticoagulant, warfarin, from its protein binding sites. It is therefore recommended that if Casodex is started in patients who are already receiving coumarin anticoagulants, prothrombin time should be closely monitored.

4.6 Pregnancy And Lactation

Casodex is contraindicated in females and must not be given to pregnant women or nursing mothers.

4.7 Effects On Ability To Drive And Use Machines

Casodex is unlikely to impair the ability of patients to drive or operate machinery. However, it should be noted that occasionally somnolence may occur. Any affected patients should exercise caution.

4.8 Undesirable Effects

In this section, undesirable effects are defined as follows: Very common (

Table 1 Frequency of Adverse Reactions

System Organ Class

Frequency

Event

Blood and lymphatic system disorders

Very common

Anaemia

Immune system disorders

Uncommon

Hypersensitivity, angioedema and urticaria

Metabolism and nutrition disorders

Common

Decreased appetite

Psychiatric disorders

Common

Decreased libido

Depression

Nervous system disorders

Very common

Dizziness

 

Common

Somnolence

Cardiac disorders

Uncommon

Cardiac failure4

Vascular disorders

Very common

Hot flush

Respiratory, thoracic and mediastinal disorders

Uncommon

Interstitial lung disease.

Fatal outcomes have been reported.

Gastrointestinal disorders

Very common

Abdominal pain

Constipation

Nausea

 

Common

Dyspepsia

Flatulence

Hepato-biliary disorders

Common

Hepatotoxicity, jaundice, raised transaminases1

 

Rare

Hepatic failure2. Fatal outcomes have been reported.

Skin and subcutaneous tissue disorders

Common

Alopecia

Hirsuitism/hair re

Dry skin

Pruritis

Rash

Renal and urinary disorders

Very common

Haematuria

Reproductive system and breast disorders

Very common

Gynaecomastia and breast tenderness3

 

Common

Erectile dysfunction

General disorders and administration site conditions

Very common

Asthenia

Oedema

 

Common

Chest pain

Investigations

Common

Weight increased

1. Hepatic changes are rarely severe and were frequently transient, resolving or improving with continued therapy or following cessation of therapy.

2. Hepatic failure has occurred rarely in patients treated with Casodex, but a causal relationship has not been established with certainty. Periodic liver function testing should be considered (see also section 4.4).

3. May be reduced by concomitant castration.

4. Observed in a pharmaco-epidemiology study of LHRH agonists and anti-androgens used in the treatment of prostate cancer. The risk appears to be increased when Casodex 50 mg was used in combination with LHRH agonists but no increase in risk was evident when Casodex 150 mg was used as a monotherapy to treat prostate cancer.

4.9 Overdose

There is no human experience of overdosage. There is no specific antidote; treatment should be symptomatic. Dialysis may not be helpful, since Casodex is highly protein bound and is not recovered unchanged in the urine. General supportive care, including frequent monitoring of vital signs, is indicated.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

Casodex is a non-steroidal antiandrogen, devoid of other endocrine activity. It binds to androgen receptors without activating gene expression, and thus inhibits the androgen stimulus. Regression of prostatic tumours results from this inhibition. Clinically, discontinuation of Casodex can result in antiandrogen withdrawal syndrome in a subset of patients.

Casodex is a racemate with its antiandrogenic activity being almost exclusively in the (R)-enantiomer.

5.2 Pharmacokinetic Properties

Casodex is well absorbed following oral administration. There is no evidence of any clinically relevant effect of food on bioavailability.

The (S)-enantiomer is rapidly cleared relative to the (R)-enantiomer, the latter having a plasma elimination half-life of about 1 week.

On daily administration of Casodex, the (R)-enantiomer accumulates about 10 fold in plasma as a consequence of its long half-life.

Steady state plasma concentrations of the (R)-enantiomer of approximately 9 microgram/ml are observed during daily administration of 50 mg doses of Casodex. At steady state the predominantly active (R)-enantiomer accounts for 99% of the total circulating enantiomers.

The pharmacokinetics of the (R)-enantiomer are unaffected by age, renal impairment or mild to moderate hepatic impairment. There is evidence that for subjects with severe hepatic impairment, the (R)-enantiomer is more slowly eliminated from plasma.

Casodex is highly protein bound (racemate 96%, R-bicalutamide 99.6%) and extensively metabolised (via oxidation and glucuronidation): Its metabolites are eliminated via the kidneys and bile in approximately equal proportions.

In a clinical study the mean concentration of R

5.3 Preclinical Safety Data

Casodex is a potent antiandrogen and a mixed function oxidase enzyme inducer in animals. Target organ changes, including tumour induction, in animals, are related to these activities. None of the findings in the preclinical testing is considered to have relevance to the treatment of advanced prostate cancer patients.

6. Pharmaceutical Particulars 6.1 List Of Excipients

Casodex includes the following excipients:

Lactose Monohydrate

Magnesium Stearate

Hypromellose

Macrogol 300

Povidone

Sodium Starch Glycolate

Titanium Dioxide (E171).

6.2 Incompatibilities

None known.

6.3 Shelf Life

5 years.

6.4 Special Precautions For Storage

Do not store above 30°C.

6.5 Nature And Contents Of Container

PVC blister/aluminium foil packs.

6.6 Special Precautions For Disposal And Other Handling

No special precautions required.

7. Marketing Authorisation Holder

AstraZeneca UK Limited,

600 Capability Green,

Luton, LU1 3LU, UK.

8. Marketing Authorisation Number(S)

17901/0005

9. Date Of First Authorisation/Renewal Of The Authorisation

18th June 2000/19th January 2006

10. Date Of Revision Of The Text

15th July 2010


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Stelara


Generic Name: Ustekinumab
Class: Skin and Mucous Membrane Agents, Miscellaneous
Chemical Name: Anti-(human interleukin 12 p40 subunit) (human monoclonal CNTO 1275 ?1-chain)-immunoglobulin G1 disulfide with human monoclonal CNTO 1275 ?-chain dimer
Molecular Formula: C6482H10004N1712O2016S46
CAS Number: 815610-63-0

REMS:

FDA approved a REMS for ustekinumab to ensure that the benefits of a drug outweigh the risks. The REMS may apply to one or more preparations of ustekinumab and consists of the following: medication guide and communication plan. See the FDA REMS page () or the ASHP REMS Resource Center ().

Introduction

Immunosuppressive agent; 1 a human IgG1 kappa monoclonal antibody directed against the p40 subunit of interleukin-12 (IL-12) and interleukin-23 (IL-23).1 2 3 4

Uses for Stelara Plaque Psoriasis

Management of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.1 2 3 4

Stelara Dosage and Administration General REMS Program

FDA has approved a Risk Evaluation and Mitigation Strategy (REMS) for ustekinumab.5

The program consists of a medication guide that must be provided to patients and a communication plan that includes initial and/or periodic communications targeting selected groups of clinicians.5

The goals are to evaluate and mitigate potential risks of serious infections, malignancy, and reversible posterior leukoencephalopathy syndrome (RPLS) by warning patients and health care providers about these risks and informing health care providers about the Psoriasis Longitudinal Assessment and Registry (PSOLAR), a voluntary, disease-specific patient registry (see Warnings/Precautions under Cautions).5

For additional information on PSOLAR, including instructions for patient enrollment, call 888-PSOLAR5 (888-776-5275) or access and search for PSOLAR.5

Administration Sub-Q Administration

Administer by sub-Q injection at a different anatomic site (e.g., upper arms, gluteal regions, thighs, any quadrant of the abdomen) than the previous injection.1 Do not make injections into areas where the skin is tender, bruised, erythematous, or indurated.1 Use a 27-gauge, ?-inch needle to administer the drug.1

Do not shake the injection.1

Injection contains no preservative; discard any unused portion.1

Intended for use under the supervision of a clinician; should only be administered by a health care provider (i.e., self-administration is not recommended).1 9 Administer only to patients who will be closely monitored and have regular follow-up visits with a clinician.1

Dosage Adults Plaque Psoriasis Sub-Q

Adults weighing ?100 kg: 45 mg at 0 and 4 weeks, then every 12 weeks.1

Adults weighing >100 kg: 90 mg at 0 and 4 weeks, then every 12 weeks.1 Although 45-mg doses were effective in these patients in clinical studies, 90-mg doses were more effective.1

Prescribing Limits Adults Psoriasis Sub-Q

Safety and efficacy not evaluated beyond 2 years.1

Special Populations Hepatic Impairment

Manufacturer makes no specific dosage recommendations.1

Renal Impairment

Manufacturer makes no specific dosage recommendations.1

Geriatric Patients

Manufacturer makes no specific dosage recommendations.1

Cautions for Stelara Contraindications

Manufacturer states none known.1

Warnings/Precautions Infectious Complications

May increase risk of infection, including reactivation of latent infections.1 Serious bacterial, fungal, and viral infections observed.1 Serious infections requiring hospitalization (e.g., cellulitis, diverticulitis, osteomyelitis, viral infections, gastroenteritis, pneumonia, urinary tract infections) reported.1

Individuals genetically deficient in IL-12/IL-23 are particularly vulnerable to disseminated infections caused by mycobacteria (including nontuberculous, environmental mycobacteria), salmonella (including nontyphi strains), and BCG vaccine; serious, sometimes fatal, infections reported in such individuals.1 Not known whether patients with ustekinumab-induced blockade of IL-12/IL-23 are susceptible to these infections.1 Consider appropriate diagnostic testing for these infections (e.g., tissue culture, stool culture) as dictated by clinical circumstances.1

Do not use ustekinumab in patients with any clinically important active infection and do not administer until the infection resolves or is adequately treated.1 If a serious infection develops, discontinue ustekinumab until infection resolves.1 Exercise caution when considering use of ustekinumab in patients with chronic infection or history of recurrent infection.1

Evaluate patients for active or latent tuberculosis prior to initiation of ustekinumab.1 Do not administer to patients with active tuberculosis.1 When indicated, initiate appropriate antimycobacterial regimen for treatment of latent tuberculosis prior to ustekinumab therapy.1 Also consider antimycobacterial therapy prior to ustekinumab therapy in individuals with a history of latent or active tuberculosis in whom an adequate course of antimycobacterial treatment cannot be confirmed.1 Closely monitor patients for active tuberculosis during and after treatment.1

Malignancies

May increase risk of malignancy.1

Malignancies reported in clinical studies;1 serious malignancies included breast, colon, head and neck, kidney, prostate, and thyroid cancers.1

Inhibition of the p40 subunit of IL-12/IL-23 increased the risk of malignancy in animals.1 Ultraviolet (UV) radiation-induced skin cancers developed earlier and more frequently in mice genetically manipulated to be deficient in both IL-12 and IL-23 or IL-12 alone.1 Relevance of these data to risk of malignancy in humans unknown.1

Safety of ustekinumab not evaluated in patients with history of malignancy or with known malignancy.1

Sensitivity Reactions Hypersensitivity Reactions

Serious allergic reactions (e.g., angioedema, dyspnea, hypotension, possible anaphylaxis) and hypersensitivity reactions (e.g., rash, urticaria) reported.1

If anaphylactic or other serious allergic reaction occurs, discontinue ustekinumab and institute appropriate therapy.1

Latex Sensitivity

The needle cover of the prefilled syringe contains dry natural rubber and should not be handled by individuals sensitive to latex.1

Reversible Posterior Leukoencephalopathy Syndrome

Reversible posterior leukoencephalopathy syndrome (RPLS), a neurologic syndrome characterized by reversible vasogenic subcortical edema,7 observed in 1 of 3523 ustekinumab-treated patients during premarketing studies.1 Patient received 12 doses of ustekinumab over approximately 2 years and presented with headache, seizures, and confusion.1 Drug was discontinued and patient fully recovered with appropriate treatment.1

RPLS reported in association with conditions such as preeclampsia, eclampsia, and acute hypertension and with cytotoxic or immunosuppressive therapy; not caused by demyelination or known infectious agent.1 7 Manifestations include visual and neurologic disturbances (e.g., headache, seizures, confusion, encephalopathy, blindness).1 7 Magnetic resonance imaging (MRI) is used to confirm diagnosis of RPLS.7

If RPLS suspected, discontinue ustekinumab and institute appropriate treatment.1

Immunization

Administer all age-appropriate vaccines prior to initiation of ustekinumab therapy.1

Avoid live vaccines.1 Do not administer BCG vaccine during, for 1 year before, or for 1 year after ustekinumab therapy.1 (See Interactions.)

Theoretical Risk of Immunotherapy

Ustekinumab not evaluated in patients who have undergone allergy immunotherapy.1

Ustekinumab may decrease protective effect of allergy immunotherapy and may increase risk of an allergic reaction to a dose of allergen immunotherapy.1

Exercise caution in patients who are receiving or who have received allergy immunotherapy, particularly for anaphylaxis.1

Immunogenicity

Testing for antibodies to ustekinumab was positive in 3–5%, negative in 8–47%, and inconclusive in 48–90% of patients in clinical studies.1 Presence of ustekinumab in serum may interfere with assay and produce inconclusive results; ustekinumab may have been present in serum when testing was performed.1

Specific Populations Pregnancy

Category B.1

Lactation

Distributed into milk in lactating monkeys.1 Since IgG distributes into human milk, ustekinumab is expected to distribute into human milk.1 Not known whether ustekinumab is absorbed systemically following ingestion; however, published data suggest that antibodies in breast milk do not enter the neonatal and infant circulation in substantial amounts.1

Caution if used in nursing women.1 Weigh unknown risks to infant (from GI or systemic exposure to ustekinumab) against known benefits of breast-feeding.1

Pediatric Use

Safety and efficacy not established in children <18 years of age.1

Geriatric Use

No apparent differences in safety and efficacy relative to younger adults; however, insufficient experience in patients ?65 years of age to determine whether they respond differently than younger adults.1

Common Adverse Effects

Nasopharyngitis,1 upper respiratory tract infection,1 headache,1 fatigue,1 diarrhea,1 back pain,1 dizziness,1 pharyngolaryngeal pain,1 pruritus,1 injection site erythema,1 myalgia,1 depression.1

Interactions for Stelara

No formal drug interaction studies to date.1

Drugs Metabolized by Hepatic Microsomal Enzymes

Because increased levels of cytokines (e.g., interleukin-1 [IL-1], interleukin-6 [IL-6], interleukin-10 [IL-10], tumor necrosis factor [TNF; TNF-?], interferon [IFN]) during chronic inflammation may suppress formation of CYP isoenzymes, ustekinumab may normalize formation of CYP enzymes.1 6 A role for IL-12 or IL-23 in regulation of CYP enzymes not reported.1

Drugs metabolized by CYP isoenzymes, particularly those with a low therapeutic index: Consider monitoring therapeutic effect and serum drug concentrations following initiation of ustekinumab; adjust dosage as needed.1

Vaccines

Avoid live vaccines.1

Use caution when administering live vaccines to household contacts of patients receiving ustekinumab because of potential risk for shedding vaccine organism from household contact and transmission to patient.1

Inactive vaccines administered during ustekinumab therapy may not elicit an immune response sufficient to prevent disease.1

Specific Drugs and Therapies

Drug or Therapy

Interaction

Comments

BCG vaccine

Individuals with genetic IL-12/IL-23 deficiency are vulnerable to disseminated infections caused by BCG vaccine1

Do not administer BCG vaccine during, for 1 year before, or for 1 year after ustekinumab therapy1

Cyclosporine

Possible effect on cyclosporine metabolism; because increased levels of cytokines during chronic inflammation may suppress formation of CYP isoenzymes, ustekinumab may normalize formation of CYP enzymes1 6

Consider monitoring cyclosporine concentrations following initiation of ustekinumab; adjust dosage as needed1

Immunosuppressive agents

Safety of concomitant therapy not established1

Phototherapy

Increased risk of UV radiation-induced skin cancers in mice with IL-12/IL-23 or IL-12 deficiency; relevance to humans unknown1

Safety of concomitant therapy not established1

Warfarin

Possible effect on warfarin metabolism; because increased levels of cytokines during chronic inflammation may suppress formation of CYP isoenzymes, ustekinumab may normalize formation of CYP enzymes1 6

Consider monitoring therapeutic effect of warfarin following initiation of ustekinumab; adjust dosage as needed1

Stelara Pharmacokinetics Absorption Bioavailability

Peak serum concentrations achieved in a median of 13.5 or 7 days following sub-Q administration of a single 45- or 90-mg dose, respectively, in patients with psoriasis.1

Steady-state concentrations achieved within 28 weeks with multiple-dose sub-Q administration.1

No apparent accumulation in serum over time when administered sub-Q every 12 weeks.1

Special Populations

When the same dose was administered regardless of body weight, patients weighing >100 kg had lower median serum ustekinumab concentrations compared with those weighing ?100 kg.1 (See Dosage under Dosage and Administration.)

Distribution Extent

Distributed into milk in lactating monkeys.1 Because IgG distributes into human milk, ustekinumab is expected to distribute into human milk.1

Special Populations

No apparent change in volume of distribution in individuals >65 years of age.1

Elimination Metabolism

Metabolic pathway not characterized.1

Expected to be degraded into small peptides and amino acids via catabolic pathways in same manner as endogenous IgG.1

Half-life

Mean half-life: 14.9–45.6 days following IV and sub-Q administration in patients with psoriasis.1

Special Populations

No apparent change in clearance in individuals >65 years of age.1

Pharmacokinetic data in patients with renal or hepatic impairment not available.1

Stability Storage Parenteral Injection

2–8°C; do not freeze.1 Store in original carton to protect from light until administration.1 Store vials upright.1 Discard any unused portion.1

Actions

Binds with high affinity and specificity to the p40 subunit of both IL-12 and IL-23.1 2 3

IL-12 and IL-23 are naturally occurring cytokines involved in inflammatory and immune responses, such as natural killer cell activation and CD4+ T-cell differentiation and activation.1 2 4

Disrupts IL-12- and IL-23-mediated signaling and cytokine cascades by disrupting the interaction of these cytokines with a shared cell-surface receptor chain, IL-12 ?1.1 2

Produced using recombinant DNA technology and purified using standard bioprocessing technology.1

Advice to Patients

A copy of the manufacturer’s patient information (medication guide) for ustekinumab must be provided to all patients with each prescription of the drug.5 Importance of instructing patients to read the medication guide prior to initiation of therapy and each time the prescription is refilled.1 (See REMS Program under Dosage and Administration.)

Importance of informing patients that ustekinumab may lower the ability of their immune system to fight infections.1 Importance of contacting clinicians if any signs or symptoms of infection develop.1

Risk of malignancies while receiving ustekinumab.1

Importance of advising patients to seek immediate medical attention if they experience any symptoms of serious allergic reactions.1

Importance of alerting clinician if allergy to latex exists.1

Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses or any history of infection.1

Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Ustekinumab

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for subcutaneous use

45 mg/0.5 mL

Stelara (available as single-use prefilled syringes and single-use vials)

Janssen Biotech, (formerly Centocor Ortho Biotech)

90 mg/mL

Stelara (available as single-use prefilled syringes and single-use vials)

Janssen Biotech, (formerly Centocor Ortho Biotech)

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions October 27, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Centocor Ortho Biotech Inc. Stelara (ustekinumab) injection prescribing information. Horsham, PA; 2010 Oct.

2. Leonardi CL, Kimball AB, Papp KA et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1). Lancet. 2008; 371:1665-74. [PubMed 18486739]

3. Papp KA, Langley RG, Lebwohl M et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2). Lancet. 2008; 371:1675-84. [PubMed 18486740]

4. Griffiths CE, Strober BE, van de Kerkhof P et al. Comparison of ustekinumab and etanercept for moderate-to-severe psoriasis. N Engl J Med. 2010; 362:118-28. [PubMed 20071701]

5. Stelara (ustekinumab) risk evaluation and mitigation strategy (REMS). From FDA website (). Accessed 2011 Feb 14.

6. Centocor Ortho Biotech Inc. Simponi (golimumab) injection prescribing information. Horsham, PA; 2011 Mar.

7. Lee VH, Wijdicks EF, Manno EM et al. Clinical spectrum of reversible posterior leukoencephalopathy syndrome. Arch Neurol. 2008; 65:205-10. [PubMed 18268188]

8. Lebwohl M, Yeilding N, Szapary P et al. Impact of weight on the efficacy and safety of ustekinumab in patients with moderate to severe psoriasis: rationale for dosing recommendations. J Am Acad Dermatol. 2010; 63:571-9. [PubMed 20599293]

9. US Food and Drug Administration. Center for Drug Evaluation and Research. Application number: 12561: Medical review(s) for ustekinumab. From FDA website (). Accessed 2011 Mar 31.

More Stelara resources Stelara Side Effects (in more detail) Stelara Use in Pregnancy & Breastfeeding Stelara Drug Interactions Stelara Support Group 11 Reviews for Stelara - Add your own review/rating Stelara Prescribing Information (FDA) Stelara Consumer Overview Stelara Advanced Consumer (Micromedex) - Includes Dosage Information Stelara MedFacts Consumer Leaflet (Wolters Kluwer) Ustekinumab Professional Patient Advice (Wolters Kluwer) Compare Stelara with other medications Psoriasis
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Cosyntropin



Cosyntropin Injection
0.25 mg/mL

FOR DIAGNOSTIC USE ONLY

For Intravenous Use Only

Cosyntropin Description

Cosyntropin Injection is a 1 mL sterile solution in vials containing 0.25 mg of Cosyntropin, 0.82 mg sodium acetate trihydrate, 6.4 mg sodium chloride, 10 mg mannitol, 1 mg glacial acetic acid, and water for injection, USP. Administration is by intravenous injection. Cosyntropin is ? 1-24 corticotropin, a synthetic subunit of ACTH. It is an open chain polypeptide containing, from the N terminus, the first 24 of the 39 amino acids of natural ACTH. The sequence of amino acids in the 1-24 compound is as follows:

Cosyntropin - Clinical Pharmacology

Cosyntropin injection exhibits the full corticosteroidogenic activity of natural ACTH. Various studies have shown that the biologic activity of ACTH resides in the N-terminal portion of the molecule and that the 1-20 amino acid residue is the minimal sequence retaining full activity. Partial or complete loss of activity is noted with progressive shortening of the chain beyond 20 amino acid residues. For example, the decrement from 20 to 19 results in a 70% loss of potency.

The pharmacologic profile of Cosyntropin injection is similar to that of purified natural ACTH. It has been established that 0.25 mg of Cosyntropin injection will stimulate the adrenal cortex maximally and to the same extent as 25 units of natural ACTH. This dose of Cosyntropin injection will produce maximal secretion of 17-OH corticosteroids, 17-ketosteroids and/or 17-ketogenic steroids.

The extra-adrenal effects which natural ACTH and Cosyntropin injection have in common include increased melanotropic activity, increased growth hormone secretion and an adipokinetic effect. These are considered to be without physiological or clinical significance.

Animal, human and synthetic ACTH (1-39) which all contain 39 amino acids exhibit similar immunologic activity. This activity resides in the C-terminal portion of the molecule and the 22-39 amino acid residues exhibit the greatest degree of antigenicity. In contrast, synthetic poly-peptides containing 1-19 or fewer amino acids have no detectable immunologic activity. Those containing 1-26, 1-24 or 1-23 amino acids have very little immunologic although full biologic activity. This property of Cosyntropin injection assumes added importance in view of the known antigenicity of natural ACTH.

Indications and Usage for Cosyntropin

Cosyntropin injection is intended for use as a diagnostic agent in the screening of patients presumed to have adrenocortical insufficiency. Because of its rapid effect on the adrenal cortex it may be utilized to perform a 30-minute test of adrenal function (plasma cortisol response) as an office or outpatient procedure, using only 2 venipunctures (see DOSAGE AND ADMINISTRATION section).

Severe hypofunction of the pituitary-adrenal axis is usually associated with subnormal plasma cortisol values but a low basal level is not per se evidence of adrenal insufficiency and does not suffice to make the diagnosis. Many patients with proven insufficiency will have normal basal levels and will develop signs of insufficiency only when stressed. For this reason a criterion which should be used in establishing the diagnosis is the failure to respond to adequate corticotropin stimulation. When presumptive adrenal insufficiency is diagnosed by a subnormal Cosyntropin injection test, further studies are indicated to determine if it is primary or secondary.

Primary adrenal insufficiency (Addison’s disease) is the result of an intrinsic disease process, such as tuberculosis within the gland. The production of adrenocortical hormones is deficient despite high ACTH levels (feedback mechanism). Secondary or relative insufficiency arises as the result of defective production of ACTH leading in turn to disuse atrophy of the adrenal cortex. It is commonly seen, for example, as result of corticosteroid therapy, Sheehan’s syndrome and pituitary tumors or ablation.

The differentiation of both types is based on the premise that a primarily defective gland cannot be stimulated by ACTH whereas a secondarily defective gland is potentially functional and will respond to adequate stimulation with ACTH. Patients selected for further study as the result of a subnormal Cosyntropin injection test should be given a 3 or 4 day course of treatment with Repository Corticotropin Injection USP and then retested. Suggested doses are 40 USP units twice daily for 4 days or 60 USP units twice daily for 3 days. Under these conditions little or no increase in plasma cortisol levels will be seen in Addison’s disease whereas higher or even normal levels will be seen in cases with secondary adrenal insufficiency.

CONTRAINDICATION

The only contraindication to Cosyntropin injection is a history of a previous adverse reaction to it.

Precautions General

Cosyntropin injection exhibits slight immunologic activity, does not contain animal protein and is therefore less risky to use than natural ACTH. Patients known to be sensitized to natural ACTH with markedly positive skin tests will, with few exceptions, react negatively when tested intradermally with Cosyntropin injection. Most patients with a history of a previous hypersensitivity reaction to natural ACTH or a pre-existing allergic disease will tolerate Cosyntropin injection. Despite this however, Cosyntropin injection is not completely devoid of immunologic activity and hypersensitivity reactions including rare anaphylaxis are possible. Therefore, the physician should be prepared, prior to injection, to treat any possible acute hypersensitivity reaction.

Drug Interactions

Corticotropin may accentuate the electrolyte loss associated with diuretic therapy.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long term studies in animals have not been performed to evaluate carcinogenic or mutagenic potential or impairment of fertility. A study in rats noted inhibition of reproductive function like natural ACTH.

Pregnancy Pregnancy Category C

Safety in pregnant women has not been established. There are no adequate and well controlled studies of Cosyntropin in pregnant women. Cosyntropin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

It is not known whether Cosyntropin is excreted into milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Cosyntropin, caution should be exercised when Cosyntropin injection is administered to a nursing woman.

Pediatric Use

(See DOSAGE AND ADMINISTRATION section.)

Adverse Reactions

Since Cosyntropin injection is intended for diagnostic and not therapeutic use, adverse reactions other than a rare hypersensitivity reaction are not anticipated. A rare hypersensitivity reaction usually associated with a pre-existing allergic disease and/or a previous reaction to natural ACTH is possible. There have been rare reports of anaphylactic reaction. The following adverse reactions have been reported in patients after the administration of Cosyntropin injection and the association has been neither confirmed nor refuted:

bradycardia tachycardia hypertension peripheral edema rash Cosyntropin Dosage and Administration

This product should not be given intramuscularly.

Cosyntropin injection may be administered as a direct intravenous injection when used as a rapid screening test of adrenal function. It may also be given as an intravenous infusion over a 4 to 8 hour period to provide a greater stimulus to the adrenal glands. Doses of Cosyntropin injection 0.25 to 0.75 mg have been used in clinical studies and a maximal response noted with the smallest dose.

A suggested method for a rapid screening test of adrenal function has been described by Wood and Associates1. A control blood sample of 6 to 7 mL is collected in a heparinized tube. The drug product should be inspected visually for particulate matter and discoloration prior to injection. Inject 1 mL of Cosyntropin injection. Discard any unused portion. In the pediatric population, aged 2 years or less, a dose of 0.125 mg will often suffice. A second blood sample is collected exactly 30 minutes later. Both blood samples should be refrigerated until sent to the laboratory for determination of the plasma cortisol response by some appropriate method. If it is not possible to send them to the laboratory or perform the fluorimetric procedure within 12 hours, then the plasma should be separated and refrigerated or frozen according to need.

Two alternative methods of administration are intravenous injection and infusion. Cosyntropin injection can be injected intravenously in 2 to 5 mL of 0.9 % Sodium Chloride Injection, USP over a 2-minute period. When given as an intravenous infusion: Cosyntropin injection, 0.25 mg/mL may be added to either 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP and given at the rate of approximately 40 micrograms per hour over a 6-hour period. It should not be added to blood or plasma as it is apt to be inactivated by enzymes. Adrenal response may be measured in the usual manner by determining urinary steroid excretion before and after treatment or by measuring plasma cortisol levels before and at the end of the infusion. The latter is preferable because the urinary steroid excretion does not always accurately reflect the adrenal or plasma cortisol response to ACTH.

The usual normal response in most cases is an approximate doubling of the basal level, provided that the basal level does not exceed the normal range. Patients receiving cortisone, hydrocortisone or spironolactone should omit their pre-test doses on the day selected for testing. Patients taking inadvertent doses of cortisone or hydrocortisone on the test day and patients taking spironolactone or women taking drugs which contain estrogen may exhibit abnormally high basal plasma cortisol levels.

A paradoxical response may be noted in the cortisone or hydrocortisone group as seen in a decrease in plasma cortisol values following a stimulating dose of Cosyntropin injection.

In the spironolactone or estrogen group only a normal incremental response is to be expected. Many patients with normal adrenal function, however, do not respond to the expected degree so that the following criteria have been established to denote a normal response:

The control plasma cortisol level should exceed 5 micrograms/100 mL. The 30-minute level should show an increment of at least 7 micrograms/100 mL above the basal level. The 30-minute level should exceed 18 micrograms/100 mL. Comparable figures have been reported by Greig and co-workers2.

If the increase in plasma cortisol levels at 30 minutes is equivocal, a consideration should be given to repeat cortisol sampling at later time points (e.g. 60 and/or 90 minutes). In a study in normal volunteers, plasma cortisol levels peaked about 2.5 ± 0.5 hours after an intravenous injection of Cosyntropin (see Fig. 1).

In patients with a raised plasma bilirubin or in patients where the plasma contains free hemoglobin, falsely high fluorescence measurements will result. The test may be performed at any time during the day but because of the physiological diurnal variation of plasma cortisol the criteria listed by Wood cannot apply. It has been shown that basal plasma cortisol levels and the post Cosyntropin injection increment exhibit diurnal changes. However, the 30-minute plasma cortisol level remains unchanged throughout the day so that only this single criterion should be used3.

Parenteral drug products should be inspected visually for particulate matter and discoloration whenever solution and container permit. Unused Cosyntropin injection should be discarded.

How is Cosyntropin Supplied

NDC 0781-3052-95 Cosyntropin Injection 0.25 mg/mL, Box of 10 - 1 mL vials

Store refrigerated between 2°-8°C (36°-46°F). Protect from light. Protect from freezing.

Cosyntropin injection is intended as a single dose injection and contains no antimicrobial preservative. Any unused portion should be discarded.

REFERENCES Wood, J.B. et al. LANCET 1.243, 1965. Greig, W.R. et al. J. ENDOCR 34.411, 1966. McGill, P.E. et al. ANN RHEUM DIS 26.123, 1967.

07-2009M

1006847

Manufactured in Canada by

Sandoz Canada Inc. for

Sandoz Inc.

Princeton, NJ 08540

PRINCIPAL DISPLAY PANEL
Cosyntropin 
Cosyntropin  injection, solution Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0781-3052 Route of Administration INTRAVENOUS DEA Schedule      Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Cosyntropin (Cosyntropin) Cosyntropin 0.25 mg  in 1 mL Inactive Ingredients Ingredient Name Strength ACETIC ACID 1 mg  in 1 mL MANNITOL 10 mg  in 1 mL SODIUM ACETATE 0.82 mg  in 1 mL SODIUM CHLORIDE 6.4 mg  in 1 mL WATER   Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains          Packaging # NDC Package Description Multilevel Packaging 1 0781-3052-95 10 VIAL In 1 BOX contains a VIAL, SINGLE-DOSE (0781-3052-71) 1 0781-3052-71 1 mL In 1 VIAL, SINGLE-DOSE This package is contained within the BOX (0781-3052-95)
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA022028 02/21/2008
Labeler - Sandoz Inc (110342024) Revised: 10/2011Sandoz Inc More Cosyntropin resources Cosyntropin Side Effects (in more detail) Cosyntropin Use in Pregnancy & Breastfeeding Cosyntropin Drug Interactions Cosyntropin Support Group 0 Reviews for Cosyntropin - Add your own review/rating Cosyntropin MedFacts Consumer Leaflet (Wolters Kluwer) Compare Cosyntropin with other medications Adrenocortical Insufficiency
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Trifluridine



Trifluridine OPHTHALMIC SOLUTION, 1% DESCRIPTION

Trifluridine Ophthalmic Solution (also known as trifluorothymidine, F3TdR, F3T), an antiviral drug for topical treatment of epithelial keratitis caused by herpes simplex virus. The chemical name of Trifluridine is ?,?,?-trifluorothymidine. Trifluridine has the following structural formula.

Trifluridine sterile ophthalmic solution contains 1% Trifluridine in an aqueous solution with acetic acid and sodium acetate (buffers), sodium chloride, and thimerosal 0.001% (added as a preservative). The pH range is 5.5 to 6.0 and osmolality is approximately 283 mOsm.

CLINICAL PHARMACOLOGY

Trifluridine is a fluorinated pyrimidine nucleoside with in vitro and in vivo activity against herpes simplex virus, types 1 and 2 and vacciniavirus. Some strains of adenovirus are also inhibited in vitro.

Trifluridine is also effective in the treatment of epithelial keratitis that has not responded clinically to the topical administration of idoxuridine or when ocular toxicity or hypersensitivity to idoxuridine has occurred. In a smaller number of patients found to be resistant to topical vidarabine, Trifluridine was also effective.

Trifluridine interferes with DNA synthesis in cultured mammalian cells. However, its antiviral mechanism of action is not completely known.

In vitro perfusion studies on excised rabbit corneas have shown that Trifluridine penetrates the intact cornea as evidenced by recovery of parental drug and its major metabolite, 5-carboxy-2?-deoxyuridine, on the endothelial side of the cornea. Absence of the corneal epithelium enhances the penetration of Trifluridine approximately two-fold.

Intraocular penetration of Trifluridine occurs after topical instillation of Trifluridine into human eyes. Decreased corneal integrity or stromal or uveal inflammation may enhance the penetration of Trifluridine into the aqueous humor. Unlike the results of ocular penetration of Trifluridine in vitro, 5-carboxy-2?-deoxyuridine was not found in detectable concentrations within the aqueous humor of the human eye.

Systemic absorption of Trifluridine following therapeutic dosing with Trifluridine appears to be negligible. No detectable concentrations of Trifluridine or 5-carboxy-2?-deoxyuridine were found in the sera of adult healthy normal subjects who had Trifluridine instilled into their eyes seven times daily for 14 consecutive days.

Clinical Studies: During a controlled multicenter clinical trial, 92 of 97 (95%) patients (78 of 81 with dendritic and 14 of 16 with geographic ulcers) responded to therapy with Trifluridine as evidenced by complete corneal re-epithelialization within the 14-day therapy period. Fifty-six of 75 (75%) patients (49 of 58 with dendritic and 7 of 17 with geographic ulcers) responded to idoxuridine therapy. The mean time to corneal reepithelialization for dendritic ulcers (6 days) and geographic ulcers (7 days) was similar for both therapies.

In other clinical studies, Trifluridine was evaluated in the treatment of herpes simplex virus keratitis in patients who were unresponsive or intolerant to the topical administration of idoxuridine or vidarabine. Trifluridine was effective in 138 of 150 (92%) patients (109 of 114 with dendritic and 29 of 36 with geographic ulcers) as evidenced by corneal re-epithelialization. The mean time to corneal re-epithelialization was 6 days for patients with dendritic ulcers and 12 days for patients with geographic ulcers.

The clinical efficacy of Trifluridine in the treatment of stromal keratitis and uveitis due to herpes simplex virus or ophthalmic infections caused by vacciniavirus and adenovirus has not been established by well-controlled clinical trials. Trifluridine has not been shown to be effective in the prophylaxis of herpes simplex virus keratoconjunctivitis and epithelial keratitis by well-controlled clinical trials. Trifluridine is not effective against bacterial, fungal or chlamydial infections of the cornea or nonviral trophic lesions.

INDICATIONS AND USAGE

Trifluridine Ophthalmic Solution is indicated for the treatment of primary keratoconjunctivitis and recurrent epithelial keratitis due to herpes simplex virus, types 1 and 2.

CONTRAINDICATIONS

Trifluridine Ophthalmic Solution is contraindicated for patients who develop hypersensitivity reactions or chemical intolerance to Trifluridine.

WARNINGS

The recommended dosage and frequency of administration should not be exceeded (See DOSAGE AND ADMINISTRATION).

PRECAUTIONS General

Trifluridine Ophthalmic Solution should be prescribed only for patients who have a clinical diagnosis of herpetic keratitis.

Trifluridine may cause mild local irritation of the conjunctiva and cornea when instilled but these effects are usually transient.

Although documented in vitro viral resistance to Trifluridine has not been reported following multiple exposure to Trifluridine, the possibility of the development of viral resistance exists.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Mutagenic Potential: Trifluridine has been shown to exert mutagenic, DNA-damaging and cell-transforming activities in various standard in vitro test systems, and clastogenic activity in Vicia faba cells. It did not induce chromosome aberrations in bone marrow cells of male or female rats following a single subcutaneous dose of 100 mg/kg, but was weakly positive in female, but not in male, rats following daily subcutaneous administration at 700mg/kg/day for 5 days.

Although the significance of these test results is not clear or fully understood, there exists the possibility that mutagenic agents may cause genetic damage in humans.

Oncogenic Potential: Lifetime carcinogenicity bioassays in rats and mice given daily subcutaneous doses of Trifluridine have been performed. Rats tested at 1.5, 7.5, and 15 mg/kg/day had increased incidences of adenocarcinomas of the intestinal tract and mammary glands, hemangiosarcomas of the spleen and liver, carcinosarcomas of the prostate gland and granulosathecal cell tumors of the ovary. Mice were tested at 1, 5 and 10 mg/kg/day; those given 10mg/kg/day Trifluridine had significantly increased incidences of adenocarcinomas of the intestinal tract and uterus. Those given 10 mg/kg/day also had a significantly increased incidence of testicular atrophy as compared to vehicle control mice.

Pregnancy Teratogenic Effects

Pregnancy Category C: Trifluridine was not teratogenic at doses up to 5 mg/kg/day (23 times the estimated human exposure) when given subcutaneously to rats and rabbits. However, fetal toxicity consisting of delayed ossification of portions of the skeleton occurred at dose levels of 2.5 and 5 mg /kg /day in rats and at 2.5 mg/kg/day in rabbits. In addition, both 2.5 and 5 mg/kg/day produced fetal death and resorption in rabbits. In both rats and rabbits, 1 mg/kg/day (5 times the estimated human exposure) was a no-effect level. There were no teratogenic or fetotoxic effects after topical application of Trifluridine (approximately 5 times the estimated human exposure) to the eyes of rabbits on the 6th through the 18th days of pregnancy. In a non-standard test, Trifluridine solution has been shown to be teratogenic when injected directly into the yolk sac of chicken eggs. There are no adequate and well-controlled studies in pregnant women. Trifluridine Ophthalmic Solution should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

It is unlikely that Trifluridine is excreted in human milk after ophthalmic instillation of Trifluridine because of the relatively small dosage (? 5mg/day), its dilution in body fluids and its extremely short half-life (approximately 12 minutes). The drug should not be prescribed for nursing mothers unless the potential benefits outweigh the potential risks.

Pediatric Use

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

Geriatric Use

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

ADVERSE REACTIONS

The most frequent adverse reactions reported during controlled clinical trials were mild, transient burning or stinging upon instillation (4.6%) and palpebral edema (2.8%). Other adverse reactions in decreasing order of reported frequency were superficial punctate keratopathy, epithelial keratopathy, hypersensitivity reaction, stromal edema, irritation, keratitis sicca, hyperemia, and increased intraocular pressure.

OVERDOSAGE

Overdosage by ocular instillation is unlikely because any excess solution should be quickly expelled from the conjunctival sac.

Acute overdosage by accidental oral ingestion of Trifluridine has not occurred. However, should such ingestion occur, the 75 mg dosage of Trifluridine in a 7.5 mL bottle of Trifluridine Ophthalmic Solution is not likely to produce adverse effects. Single intravenous doses of 1.5 to 30 mg/kg/day in children and adults with neoplastic disease produce reversible bone marrow depression as the only potentially serious toxic effect and only after three to five courses of therapy. The acute oral LD50 in the mouse and rat was 4379 mg/kg or higher.

DOSAGE AND ADMINISTRATION

Instill one drop of Trifluridine Ophthalmic Solution onto the cornea of the affected eye every 2 hours while awake for a maximum daily dosage of nine drops until the cornea ulcer has completely re-epithelialized. Following re-epithelialization, treatment for an additional 7 days of one drop every 4 hours while awake for a minimum daily dosage of five drops is recommended.

If there are no signs of improvement after 7 days of therapy or complete re-epithelialization has not occurred after 14 days of therapy, other forms of therapy should be considered. Continuous administration of Trifluridine for periods exceeding 21 days should be avoided because of potential ocular toxicity.

HOW SUPPLIED

Trifluridine Ophthalmic Solution, 1% in a 7.5 mL fill packaged in a natural plastic bottle with a natural plastic flat tip and a white plastic closure.

7.5mL-NDC 61314-044-75

Store under refrigeration 2°-8°C (36°-46°F).

ANIMAL PHARMACOLOGY AND ANIMAL TOXICOLOGY

Corneal wound healing studies in rabbits showed that Trifluridine did not significantly retard closure of epithelial wounds. However, mild toxic changes such as intracellular edema of the basal cell layer, mild thinning of the overlying epithelium and reduced strength of stromal wounds were observed.

Whereas instillation of Trifluridine into rabbit eyes during a subchronic toxicity study produced some degree of corneal epithelial thinning, a 12-month chronic toxicity study in rabbits in which Trifluridine was instilled into eyes in intermittent, multiple, full-therapy courses showed no drug-related changes in the cornea.

Rx Only

Dist. by:

FALCON Pharmaceuticals, Ltd.

Fort Worth, Texas 76134 USA

Mfd. by:

Alcon Laboratories, Inc.

Fort Worth, Texas 76134 USA

340137-0203

PRINCIPAL DISPLAY PANEL

NDC 61314-044-75      Rx Only

FALCON PHARMACEUTICALS®

Trifluridine

Ophthalmic

Solution

1%

7.5 mL STERILE

Affiliate of

ALCON LABORATORIES, INC.

QUALITY RX


Trifluridine 
Trifluridine  solution Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 61314-044 Route of Administration OPHTHALMIC DEA Schedule      Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Trifluridine (Trifluridine) Trifluridine 10 mg  in 1 mL Inactive Ingredients Ingredient Name Strength ACETIC ACID   SODIUM ACETATE   SODIUM CHLORIDE   THIMEROSAL   Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains          Packaging # NDC Package Description Multilevel Packaging 1 61314-044-75 7.5 mL In 1 BOTTLE, PLASTIC None
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA074311 05/14/2001
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 Trifluridine resources Trifluridine Side Effects (in more detail) Trifluridine Use in Pregnancy & Breastfeeding Trifluridine Support Group 0 Reviews for Trifluridine - Add your own review/rating trifluridine ophthalmic Concise Consumer Information (Cerner Multum) Viroptic Monograph (AHFS DI) Viroptic Advanced Consumer (Micromedex) - Includes Dosage Information Viroptic Drops MedFacts Consumer Leaflet (Wolters Kluwer) Compare Trifluridine with other medications Herpetic Keratitis
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Finacea


azelaic acid
Dosage Form: gel
Finacea®
(azelaic acid) Gel, 15%

For Dermatologic Use Only-Not for Ophthalmic, Oral, or Intravaginal Use

Rx only

Finacea Description

Finacea® (azelaic acid) Gel, 15%, contains azelaic acid, a naturally occurring saturated dicarboxylic acid. Chemically, azelaic acid is 1,7-heptanedicarboxylic acid, with the molecular formula C9 H16 O4, a molecular weight of 188.22, and the structural formula:

Azelaic acid is a white, odorless crystalline solid that is poorly soluble in water at 20°C (0.24%), but freely soluble in boiling water and in ethanol.

Each gram of Finacea Gel, 15%, contains 0.15 gm azelaic acid (15% w/w) as the active ingredient in an aqueous gel base containing benzoic acid (as a preservative), disodium EDTA, lecithin, medium-chain triglycerides, polyacrylic acid, polysorbate 80, propylene glycol, purified water, and sodium hydroxide to adjust pH.

Finacea - Clinical Pharmacology

The mechanism(s) by which azelaic acid interferes with the pathogenic events in rosacea are unknown.

Pharmacokinetics:

The percutaneous absorption of azelaic acid after topical application of Finacea Gel, 15%, could not be reliably determined. Mean plasma azelaic acid concentrations in rosacea patients treated with Finacea Gel, 15%, twice daily for at least 8 weeks are in the range of 42 to 63.1 ng/mL. These values are within the maximum concentration range of 24.0 to 90.5 ng/mL observed in rosacea patients treated with vehicle only. This indicates that Finacea Gel, 15%, does not increase plasma azelaic acid concentration beyond the range derived from nutrition and endogenous metabolism.

In vitro and human data suggest negligible cutaneous metabolism of 3H-azelaic acid 20% cream after topical application. Azelaic acid is mainly excreted unchanged in the urine, but undergoes some ?-oxidation to shorter chain dicarboxylic acids.

Clinical Studies

Finacea Gel, 15%, was evaluated for the treatment of mild to moderate papulopustular rosacea in 2 clinical trials comprising a total of 664 (333 active to 331 vehicle) patients. Both trials were multicenter, randomized, double-blind, vehicle-controlled 12-week studies with identical protocols. Overall, 92.5% of patients were Caucasian and 73% of patients were women, and the mean age was 49 (range 21 to 86) years. Enrolled patients had mild to moderate rosacea with a mean lesion count of 18 (range 8 to 60) inflammatory papules and pustules. Subjects without papules and pustules, with nodules, rhinophyma, or ocular involvement, and a history of hypersensitivity to propylene glycol or to any other ingredients of the study drug were excluded. Finacea Gel, 15%, or its vehicle were to be applied twice daily for 12 weeks; no other topical or systemic medication affecting the course of rosacea and/or evaluability was to be used during the studies. Patients were instructed to avoid spicy foods, thermally hot foods and drinks, and alcoholic beverages during the study, and to use only very mild soaps or soapless cleansing lotion for facial cleansing.

The primary efficacy endpoints were both

change from baseline in inflammatory lesion counts and success defined as a score of clear or minimal with at least a 2 step reduction from baseline on the Investigator's Global Assessment (IGA): CLEAR: No papules and/or pustules; no or residual erythema; no or mild to moderate telangiectasia MINIMAL: Rare papules and/or pustules; residual to mild erythema; mild to moderate telangiectasia MILD: Few papules and/or pustules; mild erythema; mild to moderate telangiectasia MILD TO MODERATE: Distinct number of papules and/or pustules; mild to moderate erythema; mild to moderate telangiectasia MODERATE: Pronounced number of papules and/or pustules; moderate erythema; mild to moderate telangiectasia MODERATE TO SEVERE: Many papules and/or pustules, occasionally with large inflamed lesions; moderate erythema; moderate degree of telangiectasia

SEVERE:

Numerous papules and/or pustules, occasionally with confluent areas of inflamed lesions; moderate or severe erythema; moderate or severe telangiectasia

Primary efficacy assessment was based on the intent-to-treat (ITT) population with last observation carried forward (LOCF).

Both studies demonstrated a statistically significant difference in favor of Finacea Gel, 15%, over its vehicle in reducing the number of inflammatory papules and pustules associated with rosacea (Table 1) and with success on the IGA in the ITT-LOCF population at the end of treatment.

Table 1. Inflammatory Papules and Pustules (ITT population)* * ITT population with last observation carried forward (LOCF);

Study One

Finacea Gel,15%

N = 164

Study One

VEHICLE

N = 165

Study Two

Finacea  Gel,15%

N = 167

Study Two

VEHICLE

N = 166

Mean Lesion

Count

Baseline 17.5 17.6 17.9 18.5

End of

Treatment* 6.8 10.5 9.0 12.1

Mean Percent

Reduction

End of

Treatment* 57.9% 39.9% 50.0% 38.2%

Although some reduction of erythema which was present in patients with papules and pustules of rosacea occurred in clinical studies, efficacy for treatment of erythema in rosacea in the absence of papules and pustules has not been evaluated.

Finacea Gel, 15%, was superior to the vehicle with regard to success based on the investigator's global assessment of rosacea on a 7-point static score at the end of treatment, (ITT population; Table 2).

Table 2. Investigator's Global Assessment at the End of Treatment* * ITT population with last observation carried forward (LOCF);

Study One

Finacea  Gel, 15%

N = 164

Study One

VEHICLE

N = 165

Study Two

Finacea  Gel, 15%

N = 167

Study Two

VEHICLE

N = 166

CLEAR, MINIMAL

or MILD at End

of Treatment

(%of Patients) 61% 40% 61% 48% Indications and Usage for Finacea

Finacea Gel, 15%, is indicated for topical treatment of inflammatory papules and pustules of mild to moderate rosacea. Although some reduction of erythema which was present in patients with papules and pustules of rosacea occurred in clinical studies, efficacy for treatment of erythema in rosacea in the absence of papules and pustules has not been evaluated. Patients should be instructed to avoid spicy foods, thermally hot foods and drinks, alcoholic beverages and to use only very mild soaps or soapless cleansing lotion for facial cleansing.

Contraindications

Finacea Gel, 15%, is contraindicated in individuals with a history of hypersensitivity to propylene glycol or any other component of the formulation.

Warnings

Finacea Gel, 15%, is for dermatologic use only, and not for ophthalmic, oral or intravaginal use.

There have been isolated reports of hypopigmentation after use of azelaic acid. Since azelaic acid has not been well studied in patients with dark complexion, these patients should be monitored for early signs of hypopigmentation.

Precautions General:

Contact with the eyes should be avoided. If sensitivity or severe irritation develops with the use of Finacea Gel, 15%, treatment should be discontinued and appropriate therapy instituted.

In a transgenic mouse study, chronic use of Finacea Gel led to an increased number of animals with papillomas at the treatment site (see PRECAUTIONS:  Carcinogenesis, Mutagenesis, and Impairment of Fertility).  The clinical relevance of the findings in animal studies to humans is not clear.

Information for Patients

Patients using Finacea Gel, 15%, should receive the following information and instructions:

Finacea Gel, 15%, is to be used only as directed by the physician. Finacea Gel, 15%, is for external use only. It is not to be used orally, intravaginally, or for the eyes. Cleanse affected area(s) with a very mild soap or a soapless cleansing lotion and pat dry with a soft towel before applying Finacea Gel, 15%. Avoid alcoholic cleansers, tinctures and astringents, abrasives and peeling agents. Avoid contact of Finacea Gel, 15%, with the mouth, eyes and other mucous membranes. If it does come in contact with the eyes, wash the eyes with large amounts of water and consult a physician if eye irritation persists. The hands should be washed following application of Finacea Gel, 15%. Cosmetics may be applied after Finacea Gel, 15%, has dried. Skin irritation (e.g., pruritus, burning, or stinging) may occur during use of Finacea Gel, 15%, usually during the first few weeks of treatment. If irritation is excessive or persists, use of Finacea Gel, 15%, should be discontinued, and patients should consult their physician (see ADVERSE REACTIONS). Avoid any foods and beverages that might provoke erythema, flushing, and blushing (including spicy food, alcoholic beverages, and thermally hot drinks, including hot coffee and tea). Patients should report abnormal changes in skin color to their physician. Avoid the use of occlusive dressings or wrappings. Drug Interactions:

There have been no formal studies of the interaction of Finacea Gel, 15%, with other drugs.

Carcinogenesis, Mutagenesis, Impairment of Fertility:

Systemic long-term animal studies have not been performed to evaluate the carcinogenic potential of azelaic acid. In a 26-week dermal carcinogenicity study using transgenic (Tg.AC) mice, Finacea Gel, 15%, and the gel vehicle, when applied once or twice daily, did not increase the number of female Tg.AC animals with papillomas at the treatment site. No statistically significant increase in the number of animals with papillomas at the treatment site was observed in male Tg.AC animals after once daily application. After twice daily application, Finacea Gel, 15%, and the gel vehicle induced a statistically significant increase in the number of male animals with papillomas at the treatment site when compared to untreated males. This suggests that the positive effect may be associated with the vehicle application. The clinical relevance of the findings in animals to humans is not clear.

Azelaic acid was not mutagenic or clastogenic in a battery of in vitro (Ames assay, HGPRT in V79 cells {Chinese hamster lung cells}, and chromosomal aberration assay in human lymphocytes) and in vivo (dominant lethal assay in mice and mouse micronucleus assay) genotoxicity tests.

Oral administration of azelaic acid at dose levels up to 2500 mg/kg/day (162 times the maximum recommended human dose based on body surface area) did not affect fertility or reproductive performance in male or female rats.

Pregnancy: Teratogenic Effects Pregnancy Category B

There are no adequate and well-controlled studies of topically administered azelaic acid in pregnant women. The experience with Finacea Gel, 15%, when used by pregnant women is too limited to permit assessment of the safety of its use during pregnancy.

Dermal embryofetal developmental toxicology studies have not been performed with azelaic acid, 15%, gel. Oral embryofetal developmental studies were conducted with azelaic acid in rats, rabbits, and cynomolgus monkeys. Azelaic acid was administered during the period of organogenesis in all three animal species. Embryotoxicity was observed in rats, rabbits, and monkeys at oral doses of azelaic acid that generated some maternal toxicity. Embryotoxicity was observed in rats given 2500 mg/kg/day (162 times the maximum recommended human dose based on body surface area), rabbits given 150 or 500 mg/kg/day (19 or 65 times the maximum recommended human dose based on body surface area) and cynomolgus monkeys given 500 mg/kg/day (65 times the maximum recommended human dose based on body surface area) azelaic acid. No teratogenic effects were observed in the oral embryofetal developmental studies conducted in rats, rabbits and cynomolgus monkeys.

An oral peri- and post-natal developmental study was conducted in rats. Azelaic acid was administered from gestational day 15 through day 21 postpartum up to a dose level of 2500 mg/kg/day. Embryotoxicity was observed in rats at an oral dose that generated some maternal toxicity (2500 mg/kg/day; 162 times the maximum recommended human dose based on body surface area). In addition, slight disturbances in the postnatal development of fetuses was noted in rats at oral doses that generated some maternal toxicity (500 and 2500 mg/kg/day; 32 and 162 times the maximum recommended human dose based on body surface area). No effects on sexual maturation of the fetuses were noted in this study.

Because animal reproduction studies are not always predictive of human response, this drug should be used only if clearly needed during pregnancy.

Nursing Mothers:

Equilibrium dialysis was used to assess human milk partitioning in vitro. At an azelaic acid concentration of 25 ?g/mL, the milk/ plasma distribution coefficient was 0.7 and the milk/buffer distribution was 1.0, indicating that passage of drug into maternal milk may occur. Since less than 4% of a topically applied dose of azelaic acid cream, 20%, is systemically absorbed, the uptake of azelaic acid into maternal milk is not expected to cause a significant change from baseline azelaic acid levels in the milk. However, caution should be exercised when Finacea Gel, 15%, is administered to a nursing mother.

Pediatric Use:

Safety and effectiveness of Finacea Gel, 15%, in pediatric patients have not been established.

Geriatric Use:

Clinical studies of Finacea Gel, 15%, did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

Adverse Reactions

Overall, treatment related adverse events, including burning, stinging/tingling, dryness/tightness/scaling, itching, and erythema/irritation/redness, were 19.4% (24/124) for Finacea Gel, 15%, and 7.1% (9/127) for the active comparator gel at 15 weeks.

In two vehicle controlled, and one active controlled U.S. clinical studies, treatment safety was monitored in 788 patients who used twice daily Finacea Gel, 15%, for 12 weeks (N=333) or for 15 weeks (N=124), or the gel vehicle (N=331) for 12 weeks.

Table 3. Cutaneous Adverse Events Occurring in ?1% of Subjects in the Rosacea Trials by Treatment Group and Maximum Intensity* * Subjects may have >1 cutaneous adverse event; thus, the sum of the frequencies of preferred terms may exceed the number of subjects with at least 1 cutaneous adverse event.

Finacea Gel, 15%

N=457 (100%)

Vehicle

N=331 (100%)

Mild

n=99

(22%)

Moderate

n=61

(13%)

Severe

n=27

(6%)

Mild

n=46

(14%)

Moderate

n=30

(9%)

Severe

n=5

(2%)

 

Burning/

stinging/

tingling 71 (16%) 42 (9%) 17 (4%) 8 (2%) 6 (2%) 2 (1%) Pruritus 29 (6%) 18 (4%) 5 (1%) 9 (3%) 6 (2%) 0 (0%)

Scaling/dry

skin/xerosis 21 (5%) 10 (2%) 5 (1%) 31 (9%) 14 (4%) 1 (<1%)

Erythema/

irritation 6 (1%) 7 (2%) 2 (<1%) 8 (2%) 4 (1%) 2 (1%)

Contact

dermatitis 2 (<1%) 3 (1%) 0 (0%) 1 (<1%) 0 (0%) 0 (0%) Edema 3 (1%) 2 (<1%) 0 (0%) 3 (1%) 0 (0%) 0 (0%) Acne 3 (1%) 1 (<1%) 0 (0%) 1 (<1%) 0 (0%) 0 (0%)

Finacea Gel, 15%, and its vehicle caused irritant reactions at the application site in human dermal safety studies. Finacea Gel, 15%, caused significantly more irritation than its vehicle in a cumulative irritation study. Some improvement in irritation was demonstrated over the course of the clinical studies, but this improvement might be attributed to subject dropouts. No phototoxicity or photoallergenicity were reported in human dermal safety studies.

In patients using azelaic acid formulations, the following additional adverse experiences have been reported rarely: worsening of asthma, vitiligo depigmentation, small depigmented spots, hypertrichosis, reddening (signs of keratosis pilaris), and exacerbation of recurrent herpes labialis.

Post-marketing safety-Skin: facial burning and irritation; Eyes: iridocyclitis on accidental exposure with Finacea Gel, 15%, to the eye (see PRECAUTIONS).

Overdosage

Finacea Gel, 15%, is intended for cutaneous use only. If pronounced local irritation occurs, patients should be directed to discontinue use and appropriate therapy should be instituted (See PRECAUTIONS).

Finacea Dosage and Administration

A thin layer of Finacea Gel, 15%, should be gently massaged into the affected areas on the face twice daily, in the morning and evening. Patients should be reassessed if no improvement is observed upon completing 12 weeks of therapy.

How is Finacea Supplied

Finacea Gel, 15%, is supplied in tubes in the following size:

Finacea Gel, 15% – 50 g tube – NDC 10922-825-02

Storage

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

Distributed under license; U.S. Patent No 6,534,070

www.myFinacea.com

© 2010, Intendis, Inc. All rights reserved. July 2010

Manufactured by Intendis Manufacturing S.p.A., Segrate, Milan, Italy

Distributed by:

Intendis
Morristown, NJ 07962

Intendis is part of the Bayer Group

6706803

Finacea Gel, 15%–50 g Tube

NDC 10922-825-02

For Dermatologic Use Only
Not For Ophthalmic Use

Finacea®
(azelaic acid) Gel 15%

50 grams


Finacea 
azelaic acid  gel Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 10922-825 Route of Administration TOPICAL DEA Schedule      Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength AZELAIC ACID (AZELAIC ACID) AZELAIC ACID 0.15 g  in 1 g Inactive Ingredients Ingredient Name Strength BENZOIC ACID   EDETATE DISODIUM   1,2-DIARACHIDOYL-SN-GLYCERO-3-PHOSPHOCHOLINE   MEDIUM-CHAIN TRIGLYCERIDES   POLYACRYLIC ACID (250000 MW)   POLYSORBATE 80   PROPYLENE GLYCOL   SODIUM HYDROXIDE   WATER   Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains          Packaging # NDC Package Description Multilevel Packaging 1 10922-825-02 1 TUBE In 1 CARTON contains a TUBE 1 50 g In 1 TUBE This package is contained within the CARTON (10922-825-02)
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA021470 10/20/2010
Labeler - Intendis Inc. (363706040) Registrant - Intendis Inc. (363706040) Establishment Name Address ID/FEI Operations Intendis Manufacturing SPA 564725468 MANUFACTURE Revised: 10/2010Intendis Inc. More Finacea resources Finacea Side Effects (in more detail) Finacea Use in Pregnancy & Breastfeeding Finacea Drug Interactions Finacea Support Group 9 Reviews for Finacea - Add your own review/rating Finacea Topical Advanced Consumer (Micromedex) - Includes Dosage Information Finacea Consumer Overview Finacea Gel MedFacts Consumer Leaflet (Wolters Kluwer) Azelex Cream MedFacts Consumer Leaflet (Wolters Kluwer) Finacea Plus Gel MedFacts Consumer Leaflet (Wolters Kluwer) Compare Finacea with other medications Acne Rosacea
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Lamisil Once


1. Name Of The Medicinal Product

Lamisil® OnceTM 1% cutaneous solution

2. Qualitative And Quantitative Composition

Each gram contains 10 mg terbinafine (as hydrochloride).

For excipients, see section 6.1.

3. Pharmaceutical Form

Cutaneous solution.

Clear to slightly opaque viscous solution.

4. Clinical Particulars 4.1 Therapeutic Indications

Treatment for tinea pedis (athlete's foot).

4.2 Posology And Method Of Administration

Adults 18 years of age and over: single administration.

Lamisil Once should be applied once on both feet, even if lesions are visible on one foot only. This ensures elimination of the fungi (dermatophytes) that might be found in areas of the foot where no lesions are visible.

Patients should wash and dry both feet and hands before applying the product. They should treat one foot, then the other.

Starting between the toes, patients should apply a thin layer evenly between and all around the toes, as well as cover the sole and sides of the foot for up to 1.5 cm. The product should be applied in the same way to the other foot, even if the skin looks healthy. The product should be left to dry to a film for 1-2 minutes. Patients should then wash their hands. Lamisil Once should not be massaged into skin.

For the best results, the treated area should not be washed for 24 hours after application. It is therefore recommended to apply Lamisil Once after a shower or bath and wait until the same time the following day before washing the feet again.

Patients should use the quantity they need to cover both feet as instructed above. Any unused medication is to be discarded.

Relief of clinical symptoms usually occurs within a few days. If there are no signs of improvement after one week, patients should see a doctor. There are no data on repeated treatment with Lamisil Once. Therefore a second treatment cannot be recommended within a particular episode of athlete's foot.

Children:

Lamisil Once has not been studied in the paediatric population. Its use is therefore not recommended in patients below 18 years of age.

The elderly:

There is no evidence to suggest that elderly patients require different dosages or experience side effects different from those in younger patients.

4.3 Contraindications

Hypersensitivity to terbinafine or any of the excipients (see 6.1. List of excipients).

4.4 Special Warnings And Precautions For Use

Lamisil Once is not recommended to treat hyperkeratotic chronic plantar tinea pedis (moccasin type).

Lamisil Once is for external use only. It should not be used on the face; it may be irritating to the eyes. In case of accidental contact with the eyes, rinse eyes thoroughly with running water. Do not swallow.

In the unlikely event of allergic reaction, the film should be removed with an organic solvent such as denatured alcohol and the feet washed with warm soapy water.

Contains alcohol; keep away from naked flames

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

No drug interactions are known with use of topical Lamisil formulations.

4.6 Pregnancy And Lactation

Animal studies did not reveal any teratogenic or embryofoetotoxic potential of terbinafine. No cases of malformations in humans have been reported with terbinafine to date. However, since clinical experience in pregnant women is very limited, Lamisil Once should be used only if clearly indicated during pregnancy.

Terbinafine is excreted in breast milk, and therefore mothers should not receive Lamisil Once whilst breast-feeding.

4.7 Effects On Ability To Drive And Use Machines

Cutaneous application of Lamisil Once does not affect the ability to drive and use machines.

4.8 Undesirable Effects

Undesirable effects include mild and transient reactions at the site of application. In very rare instances, allergic reactions may occur.

Skin and subcutaneous tissue disorders:

Very rare (<1/10,000, including isolated reports): allergic reactions such as rash, pruritus, dermatitis bullous and urticaria.

General disorders and administration site conditions

Uncommon (>1/1,000, <1/100): application site reactions such as skin dryness, skin irritation or burning sensation.

4.9 Overdose

Overdose is very unlikely to happen since the product is for single dose, cutaneous use, and the tube only contains the necessary quantity for one application. Accidental ingestion of one 4 g tube of product which contains 40 mg terbinafine is much lower than one 250 mg Lamisil tablet (oral unit dose). Should several tubes be ingested however, adverse effects similar to those observed with an overdose of Lamisil tablets (e.g. headache, nausea, epigastric pain and dizziness) are to be expected.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Antifungal for topical use (ATC code D01 A E15)

Terbinafine is an allylamine which has a broad spectrum of antifungal activity in fungal infections of the skin caused by dermatophytes such as Trichophyton (e.g. T. rubrum, T. mentagrophytes, T. verrucosum, T. violaceum), Microsporum canis and Epidermophyton floccosum. At low concentrations terbinafine is fungicidal against dermatophytes and moulds. The activity against yeasts is fungicidal (e.g. Pityrosporum orbiculare or Malassezia furfur) or fungistatic, depending on the species.

Terbinafine interferes specifically with fungal sterol biosynthesis at an early step. This leads to a deficiency in ergosterol and to an intracellular accumulation of squalene, resulting in fungal cell death. Terbinafine acts by inhibition of squalene epoxidase in the fungal cell membrane. The enzyme squalene epoxidase is not linked to the cytochrome P450 system. Terbinafine does not influence the metabolism of hormones or other drugs.

Studies in patients have shown that a single dose application of Lamisil Once 1 % cutaneous solution on both feet demonstrated efficacy in patients with tinea pedis (athlete's foot) presenting lesions between the toes, and extending to adjacent skin areas of the sides and soles of the feet. The rate of relapse/reinfection at 3 months after treatment was low: 1 person out of 8 (12.5%).

5.2 Pharmacokinetic Properties

Once applied to the skin, Lamisil Once 1 % cutaneous solution forms a film on the skin. Terbinafine in the film stays on the skin for up to 72 hours. The film quickly delivers terbinafine to the stratum corneum: at 60 minutes after application, 16 to 18% of the applied dose will be present in the stratum corneum. Delivery progressively continues and terbinafine persists in the stratum corneum for up to 13 days, at levels which are in excess of the in vitro Minimum Inhibitory Concentration for terbinafine against dermatophytes.

Systemic bioavailability is very low. An application of Lamisil Once 1 % cutaneous solution on the back, on an area of 3 times the area of both feet, resulted in exposure to terbinafine of less than 0.5% of the exposure following oral administration of a 250 mg tablet.

5.3 Preclinical Safety Data

In long-term studies (up to 1 year) in rats and dogs no marked toxic effects were seen in either species up to oral doses of about 100 mg/kg a day. At high oral doses, the liver and possibly also the kidneys were identified as potential target organs.

In a two-year oral carcinogenicity study in mice, no neoplastic or other abnormal findings attributable to treatment were made up to doses of 130 (males) and 156 (females) mg/kg a day. In a two-year oral carcinogenicity study in rats at the highest dose level, 69 mg/kg a day, an increased incidence of liver tumours was observed in males. The changes, which may be associated with peroxisome proliferation, have been shown to be species-specific since they were not seen in the carcinogenicity study in mice or in other studies in mice, dogs or monkeys.

During the studies of high dose oral terbinafine in monkeys, refractile irregularities were observed in the retina at the higher doses (non-toxic effect level was 50 mg/kg). These irregularities were associated with the presence of a terbinafine metabolite in ocular tissue and disappeared after drug discontinuation. They were no associated histological changes.

A standard battery of in vitro and in vivo genotoxicity tests revealed no evidence of a mutagenic or clastogenic potential for the drug.

No adverse effects on fertility or other reproduction parameters were observed in studies in rats or rabbits.

Repeated dermal administration of Lamisil Once 1 % cutaneous solution in rats and minipigs produces plasma terbinafine levels which are at least 50-100 times lower than the no-adverse-effect-levels established in terbinafine animal toxicity studies, so use of the product is not expected to produce any systemic adverse effect. Lamisil Once 1 % cutaneous solution was well tolerated in a variety of tolerability studies and did not cause sensitisation.

6. Pharmaceutical Particulars 6.1 List Of Excipients

Acrylates/octylacrylamide copolymer;

hydroxypropylcellulose;

medium chain triglycerides;

ethanol.

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

3 years.

6.4 Special Precautions For Storage

Store in the original package. There is no special temperature precaution for storage.

6.5 Nature And Contents Of Container

4 g aluminium laminated tube (polyethylene-aluminium-polyethylene) with a polyethylene screw cap.

6.6 Special Precautions For Disposal And Other Handling

No special requirements.

7. Marketing Authorisation Holder

Novartis Consumer Health, Horsham, RH12 5AB, UK

8. Marketing Authorisation Number(S)

PL 00030/0213

9. Date Of First Authorisation/Renewal Of The Authorisation

4 November 2005

10. Date Of Revision Of The Text

23 November 2005

Legal category: GSL


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