There are currently no drugs listed for "Myelography". See Diagnosis and Investigation.

Definition of Myelography: Myelography is an imaging examination that shows the passage of contrast material in the space around the spinal cord (the subarachnoid space) and nerve roots using a form of x-ray called fluoroscopy.



Generic Name: pyridostigmine (py rid o STIG meen)



1. Name Of The Medicinal Product

Minims Phenylephrine Hydrochloride 2.5%

2. Qualitative And Quantitative Composition

Clear, colourless, sterile eye drops containing Phenylephrine Hydrochloride Ph.Eur. 2.5% w/v.

3. Pharmaceutical Form

Sterile, single-use eye drop

4. Clinical Particulars 4.1 Therapeutic Indications

Phenylephrine is a directly acting sympathomimetic agent used topically in the eye as a mydriatic. It may be indicated to dilate the pupil for diagnostic or therapeutic procedures.

4.2 Posology And Method Of Administration

Adults

Apply one drop topically to each eye. If necessary, this dose may be repeated once only, at least one hour after the first drop.

The use of a drop of topical anaesthetic a few minutes before instillation of phenylephrine is recommended to prevent stinging.

Children and the Elderly

Apply one drop topically to the eye. It is not usually necessary to exceed this dose.

4.3 Contraindications

Patients with cardiac disease, hypertension, aneurysms, thyrotoxicosis, long-standing insulin dependent diabetes mellitus and tachycardia.

Patients on monoamine oxidase inhibitors, tricyclic antidepressants and anti-hypertensive agents (including beta-blockers).

Patients with closed angle glaucoma (unless previously treated with iridectomy) and patients with a narrow angle prone to glaucoma precipitated by mydriatics.

Hypersensitivity to phenylephrine or any component of the preparation.

4.4 Special Warnings And Precautions For Use

Use with caution in the presence of diabetes, cerebral arteriosclerosis or long-standing bronchial asthma.

To reduce the risk of precipitating an attack of narrow angle glaucoma evaluate the anterior chamber angle before use.

Ocular hyperaemia can increase the absorption of phenylephrine given topically.

Corneal clouding may occur if phenylephrine 10% is instilled when the corneal epithelium has been denuded or damaged.

Systemic absorption may be minimised by compressing the lacrimal sac at the medial canthus for one minute during and after the instillation of the drops. (This blocks the passage of the drops via the naso-lacrimal duct to the wide absorptive area of the nasal and pharyngeal mucosa. It is especially advisable in children.)

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Anti-hypertensive Agents

Topical phenylephrine should not be used as it may reverse the action of many anti-hypertensive agents with possibly fatal consequences.

Monoamine Oxidase Inhibitors

There is an increased risk of adrenergic reactions when used simultaneously with, or up to three weeks after, the administration of MAOIs.

Tricyclic Antidepressants

The pressor response to adrenergic agents and the risk of cardiac arrythmia may be potentiated in patients receiving tricyclic antidepressants (or within several days of their discontinuation).

Halothane

Because of the increased risk of ventricular fibrillation, phenylephrine should be used with caution during general anaesthesia with anaesthetic agents which sensitise the myocardium to sympathomimetics.

Cardiac Glycosides or Quinidine

There is an increased risk of arrythmias.

4.6 Pregnancy And Lactation

Safety for use during pregnancy and lactation has not been established. This product should only be used during pregnancy if it is considered by the physician to be essential.

4.7 Effects On Ability To Drive And Use Machines

May cause stinging and temporarily blurred vision. Warn patients not to drive or operate hazardous machinery until vision is clear.

4.8 Undesirable Effects

Local

Eye pain and stinging on instillation (use of a drop of topical anaesthetic a few minutes before the instillation of phenylephrine is recommended), temporarily blurred vision and photophobia, conjunctival sensitisation and allergy may occur.

Systemic

Palpitations, tachycardia, extrasystoles, cardiac arrythmias and hypertension.

Serious cardiovascular reactions including coronary artery spasm, ventricular arrythmias and myocardial infarctions have occurred following topical use of 10% phenylephrine. These sometimes fatal reactions have usually occurred in patients with pre-existing cardiovascular disease.

4.9 Overdose

Because a severe toxic reaction to phenylephrine is of rapid onset and short duration, treatment is primarily supportive. Prompt injection of a rapidly acting alpha-adrenergic blocking agent such as phentolamine (dose 2 to 5mg iv) has been recommended.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

Phenylephrine is a direct acting sympathomimetic agent. It causes mydriasis via the stimulation of alpha receptors. There is almost no cycloplegic effect.

Maximal mydriasis occurs in 60 - 90 minutes with recovery after 5 - 7 hours.

The mydriatic effects of phenylephrine can be reversed with thymoxamine.

5.2 Pharmacokinetic Properties

Phenylephrine is a weak base at physiological pH. The extent of ocular penetration is determined by the condition of the cornea. A healthy cornea presents a physical barrier, in addition to which, some metabolic activity may occur. Where the corneal epithelium is damaged, the effect of the barrier and the extent of metabolism are reduced, leading to greater absorption.

5.3 Preclinical Safety Data

The use of phenylephrine in ophthalmology has been well established for many years. No unexpected adverse safety issues were identified during the development of the Minims format.

6. Pharmaceutical Particulars 6.1 List Of Excipients

Sodium metabisulphite

Disodium edetate

Purified water

6.2 Incompatibilities

None stated.

6.3 Shelf Life

15 months.

6.4 Special Precautions For Storage

Store below 25°C. Do not freeze. Store in the original container in order to protect from light.

6.5 Nature And Contents Of Container

A sealed conical shaped polypropylene container fitted with a twist and pull off cap. Each Minims unit is overwrapped in an individual polypropylene/paper pouch. Each container holds approximately 0.5ml of solution.

6.6 Special Precautions For Disposal And Other Handling

Each Minims unit should be discarded after a single use.

7. Marketing Authorisation Holder

Chauvin Pharmaceuticals Ltd

106 London Road

Kingston-upon-Thames

Surrey

KT2 6TN

8. Marketing Authorisation Number(S)

PL 0033/0117

9. Date Of First Authorisation/Renewal Of The Authorisation

21/05/1986

10. Date Of Revision Of The Text

September 2006



Generic Name: menthol gel



Definition of Mountain Sickness / Altitude Sickness: Acute mountain sickness is an illness that can affect mountain climbers, hikers, skiers, or travelers who ascend too rapidly to high altitude (typically above 8,000 feet or 2,400 meters). This is especially for persons who normally reside at or near sea level.

Drugs associated with Mountain Sickness / Altitude Sickness

The following drugs and medications are in some way related to, or used in the treatment of Mountain Sickness / Altitude Sickness. This service should be used as a supplement to, and NOT a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners.



Generic Name: hydrochlorothiazide and triamterene (HYE dro klor oh THY a zide and trye AM ter een)



Pronunciation: MIG-li-tol



Drugs associated with Malignant Pleural Effusion

The following drugs and medications are in some way related to, or used in the treatment of Malignant Pleural Effusion. This service should be used as a supplement to, and NOT a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners.

Learn more about Malignant Pleural Effusion

Micromedex Care Notes:

Pleural Effusion Pleurisy



1. Name Of The Medicinal Product

Metrotop.

2. Qualitative And Quantitative Composition

Metronidazole BP 0.8% w/v.

3. Pharmaceutical Form

A colourless aqueous gel.

4. Clinical Particulars 4.1 Therapeutic Indications

For the treatment of malodorous fungating tumours, gravitational ulcers and decubitus ulcers (pressure sores).

4.2 Posology And Method Of Administration

For external use only. Adults: All wounds should be cleaned thoroughly. Flat wounds require a liberal application of the gel over the complete area. Cavities should be loosely packed with paraffin gauze which has been smeared in the gel. All wounds should be covered with a non-adherent dressing and a pad of lint or gauze. Sticking may occur if the appropriate dressing is not used. Use once or twice daily as necessary. Elderly: No specific instructions. Children: Where necessary, instructions apply as for adults.

4.3 Contraindications

Known hypersensitivity to metronidazole.

4.4 Special Warnings And Precautions For Use

The following statements take into account the possibility that metronidazole may be absorbed after topical application. However, there is no evidence of any significant systemic concentrations of metronidazole following topical applications. Peripheral neuropathy has been reported in association with prolonged use of metronidazole. The elimination half-life of metronidazole remains unchanged in the presence of renal failure. Such patients, however, retain the metabolite of metronidazole. The clinical significance of this is not known at present. However, in patients undergoing dialysis, metronidazole and metabolites are efficiently removed.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Some potentiation of anticoagulant therapy has been reported when metronidazole has been used with the warfarin type oral anticoagulants. Patients receiving phenobarbitone metabolise metronidazole at a much faster rate than normal, reducing the half-life to approximately 3 hours. Patients are advised not to take alcohol during systemic metronidazole therapy because of the possibility of a disulfiram-like reaction.

4.6 Pregnancy And Lactation

There is inadequate evidence of the use of metronidazole in pregnancy. Metronidazole gel cannot therefore be recommended during pregnancy or lactation where significant systemic absorption may occur unless the physician considers it essential.

4.7 Effects On Ability To Drive And Use Machines

None known.

4.8 Undesirable Effects

No adverse effects have been reported. Systemic metronidazole therapy may occasionally cause an unpleasant taste in the mouth, furred tongue, nausea, vomiting, gastrointestinal disturbance, urticaria, angioedema and anaphylaxis. Drowsiness, dizziness, headache, ataxia, skin rash, pruritus, and darkening of the urine have been reported, but rarely.

4.9 Overdose

There is no specific treatment for gross overdosage of metronidazole. Gastric lavage is recommended in cases of accidental ingestion. Uneventful recovery has followed overdosage of up to 12g taken orally. Metronidazole is readily removed from the plasma by dialysis.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

Metronidazole is a potent agent against the anaerobic bacteria which are believed to produce odorous metabolites as a result of localised tissue colonisation. The aim of the product is to provide a high concentration of metronidazole at and around the site of colonisation in a water-miscible base. This form allows surface spread and penetration within the wound accompanied by ease of aseptic application and up to 24 hours duration of action.

5.2 Pharmacokinetic Properties

There is presently no evidence of any systemic concentrations of metronidazole following topical application.

5.3 Preclinical Safety Data

No further data given.

6. Pharmaceutical Particulars 6.1 List Of Excipients

Hypromellose (4500); benzalkonium chloride solution; purified water.

6.2 Incompatibilities

None known.

6.3 Shelf Life

The shelf life shall not exceed 24 months from the date of manufacture.

6.4 Special Precautions For Storage

Do not store above 25°C. Once opened the contents should be used within 28 days of opening.

6.5 Nature And Contents Of Container

Polypropylene tubes each fitted with a plastic screw cap and tamper-evident seal and enclosed within a printed cardboard carton. Single tubes may sometimes be supplied without a carton. Pack sizes: The 15g, 30g and 60g tubes are available singly or in boxes of 12.

6.6 Special Precautions For Disposal And Other Handling

None given.

7. Marketing Authorisation Holder

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

8. Marketing Authorisation Number(S)

PL 21248/0040.

9. Date Of First Authorisation/Renewal Of The Authorisation

16th September 2005.

10. Date Of Revision Of The Text

September 2005.



Generic Name: miconazole topical (my CON a zole)



1. Name Of The Medicinal Product

Macrodantin® Capsules 100mg

2. Qualitative And Quantitative Composition

Macrodantin capsules containing 100 mg Nitrofurantoin Ph Eur in macrocrystalline form.

3. Pharmaceutical Form

The 100 mg hard gelatin capsule has an opaque yellow cap and opaque white body with the Logo 'Eaton 009' divided between the body and the cap.

4. Clinical Particulars 4.1 Therapeutic Indications

For the treatment of and prophylaxis against acute or recurrent, uncomplicated lower urinary tract infections or pyelitis either spontaneous or following surgical procedures.

Nitrofurantoin is specifically indicated for the treatment of infections when due to susceptible strains of Escherichia coli, enterococci, staphylococci, Citrobacter, Klebsiella and Enterobacter.

4.2 Posology And Method Of Administration

Dosage:

Adults

Acute Uncomplicated Urinary Tract Infections (UTIs): 50 mg four times daily for seven days.

Severe chronic recurrence (UTIs): 100 mg four times daily for seven days.

Long term suppression: 50-100 mg once a day.

Prophylaxis: 50 mg four times daily for the duration of procedure and for three days thereafter.

Children and Infants over three months of age

Acute Urinary Tract Infections: 3mg/kg day in four divided doses for seven days.

Suppressive - 1mg/kg, once a day.

For children under 25 kg body weight consideration should be given to the use of Furadantin® Suspension.

Elderly

Provided there is no significant renal impairment, in which Nitrofurantoin is contraindicated, the dosage should be that for any normal adult. See precaution and risks to elderly patients associated with long-term therapy (Section 4.8).

4.3 Contraindications

Patients suffering from renal dysfunction with a creatinine clearance of less than 60 ml/minute or elevated serum creatinine.

In infants under three months of age as well as pregnant patients at term (during labour and delivery) because of the theoretical possibility of haemolytic anaemia in the foetus or in the newborn infant due to immature erythrocyte enzyme systems.

Patients with a known hypersensitivity to nitrofurantoin or other nitrofurans.

4.4 Special Warnings And Precautions For Use

Nitrofurantoin is not effective for the treatment of parenchymal infections of unilaterally nonfunctioning kidney. A surgical cause for infection should be excluded in recurrent or severe cases.

Since pre-existing conditions may mask adverse reactions, Nitrofurantoin should be used with caution in patients with pulmonary disease, hepatic dysfunction, neurological disorders, and allergic diathesis.

Peripheral neuropathy and susceptibility to peripheral neuropathy which may become severe or irreversible has occurred and may be life threatening. Therefore, treatment should be stopped at the first signs of neural involvement (paraesthesiae).

Nitrofurantoin should be used in caution with patients with anaemia, diabetes mellitus, electrolyte imbalance, debilitating conditions and vitamin B (particularly folate) deficiency.

Acute, subacute and chronic pulmonary reactions have been observed in patients treated with nitrofurantoin. If these reactions occur, nitrofurantoin should be discontinued immediately.

Chronic pulmonary reactions (including pulmonary fibrosis and diffuse interstitial pneumonitis ) can develop insidiously, and may occur commonly in elderly patients. Close monitoring of the pulmonary conditions of patients receiving long-term therapy is warranted (especially in the elderly).

Patient should be monitored closely for signs of hepatitis (particularly in long term use). Urine may be coloured yellow or brown after taking Nitrofurantoin. Patients on Nitrofurantoin are susceptible to false positive urinary glucose (if tested for reducing substances).

Nitrofurantoin should be discontinued at any sign of haemolysis in those with suspected glucose-6-phosphate dehydrogenase deficiency.

Gastrointestinal reactions may be minimised by taking the drug with food or milk, or by adjustment of dosage.

For long-term treatment, monitor patients closely for evidence of hepatitis or pulmonary symptoms or other evidence of toxicity.

Discontinue treatment with Nitrofurantoin if otherwise unexplained pulmonary, hepatic, haematological or neurological syndromes occur.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

1. Increased absorption with food or agents delaying gastric emptying.

2. Decreased absorption with magnesium trisilicate.

3. Decreased renal excretion of Nitrofurantoin by probenecid and sulphinpyrazone.

4. Decreased anti-bacterial activity by carbonic anhydrase inhibitors and urine alkalisation.

5. Anti-bacterial antagonism by quinolone anti-infectives.

6. Interference with some tests for glucose in urine

4.6 Pregnancy And Lactation

Animal studies with Nitrofurantoin have shown no teratogenic effects. Nitrofurantoin has been in extensive clinical use since 1952, and its suitability in human pregnancy has been well documented. However, as with all other drugs, the maternal side effects may adversely affect course of pregnancy. The drug should be used at the lowest dose as appropriate for a specific indication, only after careful assessment.

Nitrofurantoin is however contraindicated in infants under three months of age and in pregnant women during labour and delivery, because of the possible risk of haemolysis of the infants' immature red cells. Caution should be exercised while breast feeding an infant known or suspected to have an erythrocyte enzyme deficiency, since Nitrofurantoin is detected in trace amounts in breast milk.

4.7 Effects On Ability To Drive And Use Machines

Nitrofurantoin may cause dizziness and drowsiness and the patient should not drive or operate machinery if affected this way.

4.8 Undesirable Effects

Respiratory

If any of the following reactions occur the drug should be discontinued.

Acute pulmonary reactions usually occur within the first week of treatment and are reversible with cessation of therapy. Acute pulmonary reactions are commonly manifested by fever, chills, cough, chest pain, dyspnoea, pulmonary infiltration with consolidation or pleural effusion on chest x-ray, and eosinophilia. In subacute pulmonary reactions, fever and eosinophilia occur less often than in the acute form.

Chronic pulmonary reactions occur rarely in patients who have received continuous therapy for six months or longer and are more common in elderly patients. Changes in ECG have occurred, associated with pulmonary reactions.

Minor symptoms such as fever, chills, cough and dyspnoea may be significant. Collapse and cyanosis have been reported rarely. The severity of chronic pulmonary reactions and their degree of resolution appear to be related to the duration of therapy after the first clinical signs appear. It is important to recognise symptoms as early as possible. Pulmonary function may be impaired permanently, even after cessation of therapy.

Hepatic

Hepatic reactions including cholestatic jaundice and chronic active hepatitis occur rarely.

Fatalities have been reported. Cholestatic jaundice is generally associated with short-term therapy (usually up to two weeks). Chronic active hepatitis, occasionally leading to hepatic necrosis is generally associated with long-term therapy (usually after six months). The onset may be insidious. Treatment should be stopped at the first sign of hepatotoxicity.

Neurological

Peripheral neuropathy (including optical neuritis) with symptoms of sensory as well as motor involvement, which may become severe or irreversible, has been reported infrequently. Less frequent reactions of unknown causal relationship are depression, euphoria, confusion, psychotic reactions, nystagmus, vertigo, dizziness, asthenia, headache and drowsiness. Treatment should be stopped at the first sign of neurological involvement.

Gastrointestinal

Nausea and anorexia have been reported. Emesis, abdominal pain and diarrhoea are less common gastrointestinal reactions.

Haematological

Agranulocytosis, leucopenia, granulocytopenia, haemolytic anaemia, thrombocytopenia and megaloblastic anaemia, glucose-6-phosphate dehydrogenase deficiency anaemia, and eosinophilia have been reported. Aplastic anaemia has been reported rarely. Cessation of therapy has generally returned the blood picture to normal.

Hypersensitivity

Allergic skin reactions manifesting as angioneurotic oedema, maculopapular, erythematous or eczematous eruptions, urticaria, and pruritus have occurred.

Lupus-like syndrome associated with pulmonary reaction to Nitrofurantoin has been reported.

Exfoliative dermatitis and erythema multiforme (including Stevens-Johnson Syndrome) have been reported rarely.

Other hypersensitivity reactions include anaphylaxis, sialadenitis, pancreatitis, drug fever, and arthralgia.

Miscellaneous

Transient alopecia and benign intracranial hypertension. As with other antimicrobial agents, superinfections by fungi or resistant organisms such as Pseudomonas may occur. However, these are limited to the genito-urinary tract because suppression of normal bacterial flora does not occur elsewhere in the body

4.9 Overdose

Symptoms and signs of overdose include gastric irritation, nausea and vomiting. There is no known specific antidote. However, Nitrofurantoin can be haemodialysed in cases of recent ingestion. Standard treatment is by induction of emesis or by gastric lavage. Monitoring of full blood count, liver function, and pulmonary function tests are recommended. A high fluid intake should be maintained to promote urinary excretion of the drug.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

Macrodantin is a broad spectrum antibacterial agent, active against the majority of urinary pathogens. The wide range of organisms sensitive to the bactericidal activity include:

Escherichia coli

Enterococcus Faecalis

Klebsiella Species

Enterobacter Species

Staphylococcus Species, e.g. S.Aureus, S.Saprophyticus, S.Epidermidis

Citrobacter Species

Clinically most common urinary pathogens are sensitive to Nitrofurantoin.

Most strains of proteus and serratia are resistant. All pseudomonas strains are resistant.

5.2 Pharmacokinetic Properties

The Nitrofurantoin macrocrystals of Macrodantin are specially formulated. The controlled crystal size is designed to control the speed of absorption and thus reduce the incidence of nausea. Clinical and animal studies indicate that Macrodantin therapy decreases the likelihood of nausea in patients who might experience these symptoms on Nitrofurantoin therapy. This special formulation of Nitrofurantoin had not caused any decrease in antibacterial efficacy.

Orally administered Macrodantin is readily absorbed in the upper gastrointestinal tract at a slower rate and to reduced extent when compared to microcrystalline Nitrofurantoin. Blood concentrations at therapeutic dosage are usually low with an elimination half-life of about 30 minutes or less.

Maximum urinary excretion usually occurs 4-5 hours after administration of macrocrystalline Nitrofurantoin. Urinary drug dose recoveries of about 25-30% are obtained

5.3 Preclinical Safety Data

Carcinogenic effect of nitrofurantoin in animal studies was observed. However, human data and extensive use of nitrofurantoin over 50 years do not support such observations.

6. Pharmaceutical Particulars 6.1 List Of Excipients

The capsule fill contains lactose monohydrate, maize starch and purified talc. The capsule shell contains quinoline yellow (E104), titanium dioxide (E171), gelatin, sodium lauryl sulphate. The printing ink contains shellac and black iron oxide (E172).

6.2 Incompatibilities

Not known.

6.3 Shelf Life

Three years

6.4 Special Precautions For Storage

Storage temperature must not exceed 30oC.

6.5 Nature And Contents Of Container

Macrodantin 100 mg capsules are supplied in a PVC/aluminium foil blister pack of 30. Each pack comprises 3 blister cards containing 10 capsules on each card.

6.6 Special Precautions For Disposal And Other Handling

Macrodantin should be used as directed by physician.

A patient information leaflet is provided with details of use and handling of the product.

7. Marketing Authorisation Holder

Goldshield Pharmaceuticals Ltd

NLA Tower

12-16 Addiscombe Road

Croydon

CR0 0XT

United Kingdom

8. Marketing Authorisation Number(S)

PL 12762/0049

9. Date Of First Authorisation/Renewal Of The Authorisation

31/03/2000 / 24/05/2002

10. Date Of Revision Of The Text

13/08/2010



1. Name Of The Medicinal Product

Methotrexate Injection 5mg/2ml., Methotrexate Injection 25 mg/ml and Methotrexate Injection 100 mg/ml

2. Qualitative And Quantitative Composition

Active Constituent

 

 

5 mg/2 ml

25 mg/ml

100 mg/ml

Methotrexate

Ph Eur

5 mg

25 mg

100 mg

Other Constituents

 

 

 

 

 

 

 

 

Sodium Chloride

BP

17.2 mg

4.9 mg

None

Sodium Hydroxide

BP

QS

QS

QS

Water for Injections

BP

To 2 ml

To 1 ml

To 1 ml

There is a 5 % manufacturing overage included in the formulation.

3. Pharmaceutical Form

Sterile solution of Methotrexate in Water for Injections.

4. Clinical Particulars 4.1 Therapeutic Indications

Methotrexate is indicated in the treatment of neoplastic disease, such as trophoblastic neoplasms and leukaemia, and the symptomatic treatment of severe recalcitrant disabling psoriasis which is not adequately responsive to other forms of therapy.

Methotrexate Injection B.P. may be given by the intramuscular, intravenous, intra-arterial, intrathecal routes.

Note: Methotrexate Injection B.P, 1g /10ml and 5g /50ml presentations are hypertonic and therefore are not suitable for intrathecal use. In addition, the 500mg/20ml and 1g/40ml presentations are not suitable for intrathecal use

4.2 Posology And Method Of Administration

Adults and children

Antineoplastic Chemotherapy

Methotrexate is active orally and parenterally. Methotrexate Injection B.P. may be given by the intramuscular, intravenous, intra-arterial or intrathecal routes. Dosage is related to the patient's body weight or surface area. Methotrexate has been used with beneficial effect in a wide variety of neoplastic diseases, alone and in combination with other cytotoxic agents.

Note: Methotrexate Injection B.P, 1g /10ml and 5g /50ml presentations are hypertonic and therefore are not suitable for intrathecal use. In addition, the 500mg/20ml and 1g/40ml presentations are not suitable for intrathecal use

Choriocarcinoma and Similar Trophoblastic Diseases

Methotrexate is administered orally or intramuscularly in doses of 15-30mg daily for a 5 day course. Such courses may be repeated 3-5 times as required, with rest periods of one or more weeks interposed between courses until any manifesting toxic symptoms subside.

The effectiveness of therapy can be evaluated by 24 hours quantitative analysis of urinary chorionic gonadotrophin hormone (HCG). Combination therapy with other cytotoxic drugs, has also been reported as useful.

Hydatidiform mole may precede or be followed by choriocarcinoma, and Methotrexate has been used in similar doses for the treatment of hydatidiform mole and chorioadenoma destruens.

Breast Carcinoma

Prolonged cyclic combination with Cyclophosphamide, Methotrexate and Fluorouracil has given good results when used as adjuvant treatment to radical mastectomy in primary breast cancer with positive axillary lymph nodes. Methotrexate dosage was 40mg/m2 intravenously on the first and eighth days.

Leukaemia

Acute granulocytic leukaemia is rare in children but common in adults and this form of leukaemia responds poorly to chemotherapy.

Methotrexate is not generally a drug of choice for induction of remission of lymphoblastic leukaemia. Oral Methotrexate dosage 3.3mg/m2 daily, and Prednisolone 40-60mg/m2 daily for 4-6 weeks has been used. After a remission is attained, Methotrexate in a maintenance dosage of 20-30mg/m2 orally or by I.M. injection has been administered twice weekly. Twice weekly doses appear to be more effective than daily drug administration. Alternatively, 2.5mg/kg has been administered I.V. every 14 days.

Meningeal Leukaemia

Some patients with leukaemia are subject to leukaemic invasions of the central nervous system and the CSF should be examined in all leukaemia patients.

Passage of Methotrexate from blood to the cerebrospinal fluid is minimal and for adequate therapy the drug should be administered intrathecally. Methotrexate may be given in a prophylactic regimen in all cases of lymphocytic leukaemia. Methotrexate is administered by intrathecal injection in doses of 200-500 microgram/kg body weight. The administration is at intervals of 2 to 5 days and is usually repeated until the cell count of cerebrospinal fluid returns to normal. At this point one additional dose is advised. Alternatively, Methotrexate 12mg/m2 can be given once weekly for 2 weeks, and then once monthly. Large doses may cause convulsions and untoward side effects may occur as with any intrathecal injection, and are commonly neurological in character.

Note: Methotrexate Injection B.P, 1g /10ml and 5g /50ml presentations are hypertonic and therefore are not suitable for intrathecal use. In addition, the 500mg/20ml and 1g/40ml presentations are not suitable for intrathecal use.

Lymphomas

In Burkitt's Tumour, stages 1-2, Methotrexate has prolonged remissions in some cases. Recommended dosage is 10-25mg per day orally for 4 to 8 days. In stage 3, Methotrexate is commonly given concomitantly with other antitumour agents. Treatment in all stages usually consists of several courses of the drug interposed with 7 to 10 day rest periods, and in stage 3 they respond to combined drug therapy with Methotrexate given in doses of 0.625mg to 2.5mg/kg daily. Hodgkin's Disease responds poorly to Methotrexate and to most types of chemotherapy.

Mycosis Fungoides

Therapy with Methotrexate appears to produce clinical remissions in one half of the cases treated. Recommended dosage is usually 2.5 to 10mg daily by mouth for weeks or months and dosage should be adjusted according to the patient's response and haematological monitoring. Methotrexate has also been given intramuscularly in doses of 50mg once weekly or 25mg twice weekly.

Psoriasis Chemotherapy

Cases of severe uncontrolled psoriasis, unresponsive to conventional therapy, have responded to weekly single, oral, I.M. or I.V. doses of 10-25mg per week, and adjusted according to the patient's response. An initial test dose one week prior to initiation of therapy is recommended to detect any idiosyncrasy. A suggested dose range is 5-10mg.

An alternative dosage schedule consists of 2.5 to 5mg of Methotrexate administered orally at 12 hour intervals for 3 doses each week or at 8-hour intervals for 4 doses each week; weekly dosages should not exceed 30mg.

A daily oral dosage schedule of 2 to 5mg administered orally for 5 days followed by a rest period of at least 2 days may also be used. The daily dose should not exceed 6.25mg.

The patient should be fully informed of the risks involved and the clinician should pay particular attention to the appearance of liver toxicity by carrying out liver function tests before starting Methotrexate treatment, and repeating these at 2 to 4 month intervals during therapy. The aim of therapy should be to reduce the dose to the lowest possible level with the longest possible rest period. The use of Methotrexate may permit the return to conventional topical therapy which should be encouraged.

4.3 Contraindications

Significantly impaired renal function.

Significantly impaired hepatic function

Pre-existing blood dyscrasias, such as significant marrow hypoplasia, leukopenia, thrombocytopenia or anaemia.

Methotrexate is contraindicated in pregnancy.

Because of the potential for serious adverse reactions from methotrexate in breast fed infants, breast feeding is contra-indicated in women taking methotrexate.

Patients with a known allergic hypersensitivity to methotrexate should not receive methotrexate.

4.4 Special Warnings And Precautions For Use

WARNINGS

Methotrexate must be used only by physicians experienced in antimetabolite chemotherapy.

Because of the possibility of fatal or severe toxic reactions, the patient should be fully informed by the physician of the risks involved and be under his constant supervision.

Deaths have been reported with the use of Methotrexate in the treatment of psoriasis.

In the treatment of psoriasis, Methotrexate should be restricted to severe recalcitrant, disabling psoriasis which is not adequately responsive to other forms of therapy, but only when the diagnosis has been established by biopsy and/or after dermatological consultation.

1. Full blood counts should be closely monitored before, during and after treatment. If a clinically significant drop in white-cell or platelet count develops, methotrexate should be withdrawn immediately. Patients should be advised to report all symptoms or signs suggestive of infection.

2. Methotrexate may be hepatotoxic, particularly at high dosage or with prolonged therapy. Liver atrophy, necrosis, cirrhosis, fatty changes, and periportal fibrosis have been reported. Since changes may occur without previous signs of gastrointestinal or haematological toxicity, it is imperative that hepatic function be determined prior to initiation of treatment and monitored regularly throughout therapy. If substantial hepatic function abnormalities develop, methotrexate dosing should be suspended for at least 2 weeks.Special caution is indicated in the presence of pre-existing liver damage or impaired hepatic function. Concomitant use of other drugs with hepatotoxic potential (including alcohol) should be avoided.

3. Methotrexate has been shown to be teratogenic; it has caused foetal death and/or congenital anomalies. Therefore it is not recommended in women of childbearing potential unless there is appropriate medical evidence that the benefits can be expected to outweigh the considered risks. Pregnant psoriatic patients should not receive Methotrexate.

4. Renal function should be closely monitored before, during and after treatment. Caution should be exercised if significant renal impairment is disclosed. Reduce dose of methotrexate in patients with renal impairment. High doses may cause the precipitation of methotrexate or its metabolites in the renal tubules. A high fluid throughput and alkalinisation of the urine to pH 6.5 – 7.0, by oral or intravenous administration of sodium bicarbonate (5 x 625mg tablets every three hours) or acetazolamide (500mg orally four times a day) is recommended as a preventative measure . Methotrexate is excreted primarily by the kidneys. Its use in the presence of impaired renal function may result in accumulation of toxic amounts or even additional renal damage.

5. Diarrhoea and ulcerative stomatitis are frequent toxic effects and require interruption of therapy, otherwise haemorrhagic enteritis and death from intestinal perforation may occur.

6. Methotrexate affects gametogenesis during the period of its administration and may result in decreased fertility which is thought to be reversible on discontinuation of therapy. Conception should be avoided during the period of Methotrexate administration and for at least 6 months thereafter. Patients and their partners should be advised to this effect.

7. Methotrexate has some immunosuppressive activity and immunological responses to concurrent vaccination may be decreased. The immunosuppressive effect of Methotrexate should be taken into account when immune responses of patients are important or essential.

8. Pleural effusions and ascites should be drained prior to initiation of methotrexate therapy.

9. Deaths have been reported with the use of methotrexate. Serious adverse reactions including deaths have been reported with concomitant administration of methotrexate (usually in high doses) along with some non-steroidal anti-inflammatory drugs (NSAIDs).

10. Concomitant administration of folate antagonists such as trimethoprim/sulphamethoxazole has been reported to cause an acute megaloblastic pancytopenia in rare instances.

11. Systemic toxicity may occur following intrathecal administration. Blood counts should be monitored closely.

12. A chest X-ray is recommended prior to initiation of methotrexate therapy.

13. If acute methotrexate toxicity occurs, patients may require folinic acid.

PRECAUTIONS

Methotrexate has a high potential toxicity, usually dose related, and should be used only by physicians experienced in antimetabolite chemotherapy, in patients under their constant supervision. The physician should be familiar with the various characteristics of the drug and its established clinical usage.

Before beginning methotrexate therapy or reinstituting methotrexate after a rest period, assessment of renal function, liver function and blood elements should be made by history, physical examination and laboratory tests.

It should be noted that intrathecal doses are transported into the cardiovascular system and may give rise to systemic toxicity. Systemic toxicity of methotrexate may also be enhanced in patients with renal dysfunction, ascites, or other effusions due to prolongation of serum half-life.

Carcinogenesis, mutagenesis, and impairment of fertility: Animal carcinogenicity studies have demonstrated methotrexate to be free of carcinogenic potential. Although methotrexate has been reported to cause chromosomal damage to animal somatic cells and bone marrow cells in humans, these effects are transient and reversible. In patients treated with methotrexate, evidence is insufficient to permit conclusive evaluation of any increased risk of neoplasia.

Methotrexate has been reported to cause impairment of fertility, oligospermia, menstrual dysfunction and amenorrhoea in humans, during and for a short period after cessation of therapy. In addition, methotrexate causes, embryotoxicity, abortion and foetal defects in humans. Therefore the possible risks of effects on reproduction should be discussed with patients of childbearing potential (see 'Warnings').

Patients undergoing therapy should be subject to appropriate supervision so that signs or symptoms of possible toxic effects or adverse reactions may be detected and evaluated with minimal delay. Pretreatment and periodic haematological studies are essential to the use of Methotrexate in chemotherapy because of its common effect of haematopoietic suppression. This may occur abruptly and on apparent safe dosage, and any profound drop in blood cell count indicates immediate stopping of the drug and appropriate therapy. In patients with malignant disease who have pre-existing bone marrow aplasia, leukopenia, thrombocytopenia or anaemia, methotrexate should be used with caution, if at all.

In general, the following laboratory tests are recommended as part of essential clinical evaluation and appropriate monitoring of patients chosen for or receiving Methotrexate therapy: complete haemogram; haematocrit; urinalysis; renal function tests; liver function tests and chest X-ray.

The purpose is to determine any existing organ dysfunction or system impairment. The tests should be performed prior to therapy, at appropriate periods during therapy and after termination of therapy.

Liver biopsy may be considered after cumulative doses> 1.5g have been given, if hepatic impairment is suspected.

Methotrexate is bound in part to serum albumin after absorption, and toxicity may be increased because of displacement by certain drugs such as salicylates, sulphonamides, phenytoin, and some antibacterials such as tetracycline, chloramphenicol and para-aminobenzoic acid. These drugs, especially salicylates and sulphonamides, whether antibacterial, hypoglycaemic or diuretic, should not be given concurrently until the significance of these findings is established.

Vitamin preparations containing folic acid or its derivatives may alter response to Methotrexate.

Methotrexate should be used with extreme caution in the presence of infection, peptic ulcer, ulcerative colitis, debility, and in extreme youth and old age. If profound leukopenia occurs during therapy, bacterial infection may occur or become a threat. Cessation of the drug and appropriate antibiotic therapy is usually indicated. In severe bone marrow depression, blood or platelet transfusions may be necessary.

Since it is reported that Methotrexate may have an immunosuppressive action, this factor must be taken into consideration in evaluating the use of the drug where immune responses in a patient may be important or essential.

In all instances where the use of Methotrexate is considered for chemotherapy, the physician must evaluate the need and usefulness of the drug against the risks of toxic effects or adverse reactions. Most such adverse reactions are reversible if detected early. When such effects or reactions do occur, the drug should be reduced in dosage or discontinued and appropriate corrective measures should be taken according to the clinical judgement of the physician. Reinstitution of Methotrexate therapy should be carried out with caution, with adequate consideration of further need for the drug and alertness as to the possible recurrence of toxicity.

Methotrexate given concomitantly with radiotherapy may increase the risk of soft tissue necrosis and osteonecrosis.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Methotrexate is extensively protein bound and may be displaced by certain drugs such as salicylates, hypoglycaemics, diuretics, sulphonamides, diphenylhydantoins, tetracyclines, chloramphenicol and p-aminobenzoic acid, and the acidic anti-inflammatory agents, so causing a potential for increased toxicity when used concurrently.

Concomitant use of other drugs with nephrotoxic or hepatotoxic potential (including alcohol) should be avoided.

Vitamin preparations containing folic acid or its derivatives may decrease the effectiveness of methotrexate.

Caution should be used when NSAIDs and salicylates are administered concomitantly with methotrexate. These drugs have been reported to reduce the tubular secretion of methotrexate and thereby may enhance its toxicity. Concomitant use of NSAIDs and salicylates has been associated with fatal methotrexate toxicity.

However, patients using constant dosage regimens of NSAIDs have received concurrent doses of methotrexate without problems observed.

Renal tubular transport is also diminished by probenecid and penicillins; use of these with methotrexate should be carefully monitored.

Severe bone marrow depression has been reported following the concurrent use of methotrexate and co-trimoxazole or trimethoprim. Concurrent use should probably be avoided.

Methotrexate-induced stomatitis and other toxic effects may be increased by the use of nitrous oxide.

An increased risk of hepatitis has been reported following the use of methotrexate and the acitretin metabolite, etretinate. Consequently, the concomitant use of methotrexate and acitretin should be avoided.

4.6 Pregnancy And Lactation

Abortion, foetal death, and/or congenital anomalies have occurred in pregnant women receiving Methotrexate, especially during the first trimester of pregnancy. Methotrexate is contraindicated in the management of psoriasis or rheumatoid arthritis in pregnant women. Women of childbearing potential should not receive Methotrexate until pregnancy is excluded. For the management of psoriasis or rheumatoid arthritis, Methotrexate therapy in women should be started immediately following a menstrual period and appropriate measures should be taken in men or women to avoid conception during and for at least 6 months following cessation of Methotrexate therapy.

Both men and women receiving Methotrexate should be informed of the potential risk of adverse effects on reproduction. Women of childbearing potential should be fully informed of the potential hazard to the foetus should they become pregnant during Methotrexate therapy. In cancer chemotherapy, Methotrexate should not be used in pregnant women or women of childbearing potential who might become pregnant unless the potential benefits to the mother outweigh the possible risks to the foetus.

Defective oogenesis or spermatogenesis, transient oligospermia, menstrual dysfunction, and infertility have been reported in patients receiving Methotrexate.

Methotrexate is distributed into breast milk. Because of the potential for serious adverse reactions to Methotrexate in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.

4.7 Effects On Ability To Drive And Use Machines

Not applicable

4.8 Undesirable Effects

The most common adverse reactions include ulcerative stomatitis, leukopenia, nausea and abdominal distress. Although very rare, anaphylactic reactions to methotrexate have occurred. Others reported are malaise, undue fatigue, chills and fever, dizziness and decreased resistance to infection. In general, the incidence and severity of side effects are considered to be dose-related. Adverse reactions as reported for the various systems are as follows:

Skin: Stevens-Johnson syndrome, epidermal necrolysis, erythematous rashes, pruritus, urticaria, photosensitivity, pigmentary changes, alopecia, ecchymosis, telangiectasia, acne, furunculosis. Lesions of psoriasis may be aggravated by concomitant exposure to ultraviolet radiation. Skin ulceration in psoriatic patients and rarely painful erosion of psoriatic plaques have been reported. The recall phenomenon has been reported in both radiation and solar damaged skin.

Blood: Bone marrow depression, leukopenia, thrombocytopenia, anaemia, hypogammaglobulinaemia, haemorrhage from various sites, septicaemia.

Alimentary System: Gingivitis, pharyngitis, stomatitis, anorexia, vomiting, diarrhoea, haematemesis, melaena, gastrointestinal ulceration and bleeding, enteritis, hepatic toxicity resulting in active liver atrophy, necrosis, fatty metamorphosis, periportal fibrosis, or hepatic cirrhosis. In rare cases the effect of methotrexate on the intestinal mucosa has led to malabsorption or toxic megacolon.

Hepatic: Hepatic toxicity resulting in significant elevations of liver enzymes, acute liver atrophy, necrosis, fatty metamorphosis, periportal fibrosis or cirrhosis or death may occur, usually following chronic administration.

Urogenital System: Renal failure, azotaemia, cystitis, haematuria, defective oogenesis or spermatogenesis, transient oligospermia, menstrual dysfunction, infertility, abortion, foetal defects, severe nephropathy. Vaginitis, vaginal ulcers, cystitis, haematuria and nephropathy have also been reported.

Pulmonary System: Infrequently an acute or chronic interstitial pneumonitis, often associated with blood eosinophilia, may occur and deaths have been reported. Acute pulmonary oedema has also been reported after oral and intrathecal use. Pulmonary fibrosis is rare. A syndrome consisting of pleuritic pain and pleural thickening has been reported following high doses.

Central Nervous System: Headaches, drowsiness, blurred vision, aphasia, hemiparesis and convulsions have occurred possibly related to haemorrhage or to complications from intra-arterial catheterization. Convulsion, paresis, Guillain-Barre syndrome and increased cerebrospinal fluid pressure have followed intrathecal administration.

Other reactions related to, or attributed to the use of Methotrexate such as pneumonitis, metabolic changes, precipitation of diabetes, osteoporotic effects, abnormal changes in tissue cells and even sudden death have been reported.

There have been reports of leukoencephalopathy following intravenous methotrexate in high doses, or low doses following cranial-spinal radiation.

Adverse reactions following intrathecal methotrexate are generally classified into three groups, acute, subacute, and chronic. The acute form is a chemical arachnoiditis manifested by headache, back or shoulder pain, nuchal rigidity, and fever. The subacute form may include paresis, usually transient, paraplegia, nerve palsies, and cerebellar dysfunction. The chronic form is a leukoencephalopathy manifested by irritability, confusion, ataxia, spasticity, occasionally convulsions, dementia, somnolence, coma, and rarely, death. There is evidence that the combined use of cranial radiation and intrathecal methotrexate increases the incidence of leukoencephalopathy.

Additional reactions related to or attributed to the use of methotrexate such as osteoporosis, abnormal (usually 'megaloblastic') red cell morphology, precipitation of diabetes, other metabolic changes, and sudden death have been reported.

4.9 Overdose

Calcium Folinate (Calcium Leucovorin) is a potent agent for neutralizing the immediate toxic effects of Methotrexate on the haematopoietic system. Where large doses or overdoses are given, Calcium Folinate may be administered by intravenous infusion in doses up to 75mg within 12 hours, followed by 12mg intramuscularly every 6 hours for 4 doses. Where average doses of Methotrexate appear to have an adverse effect 6-12mg of Calcium Folinate may be given intramuscularly every 6 hours for 4 doses. In general, where overdosage is suspected, the dose of Calcium Folinate should be equal to or higher than, the offending dose of Methotrexate and should be administered as soon as possible; preferably within the first hour and certainly within 4 hours after which it may not be effective.

Other supporting therapy such as blood transfusion and renal dialysis may be required. Effective clearance of methotrexate has been reported with acute, intermittent haemodialysis using a high flux dialyser.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

Methotrexate is an antimetabolite which acts principally by competitively inhibiting the enzyme, dihydrofolate reductase. In the process of DNA synthesis and cellular replication, folic acid must be reduced to tetrahydrofolic acid by this enzyme, and inhibition by Methotrexate interferes with tissue cell reproduction. Actively proliferating tissues such as malignant cells are generally more sensitive to this effect of Methotrexate. It also inhibits antibody synthesis.

Methotrexate also has immunosuppressive activity, in part possibly as a result of inhibition of lymphocyte multiplication. The mechanism(s) of action in the management of rheumatoid arthritis of the drug is not known, although suggested mechanisms have included immunosuppressive and/or anti-inflammatory effect.

5.2 Pharmacokinetic Properties

In doses of 0.1mg (of Methotrexate) per kg, Methotrexate is completely absorbed from the G.I. tract; larger oral doses may be incompletely absorbed. Peak serum concentrations are achieved within 0.5 - 2 hours following I.V. / I.M. or intra-arterial administration. Serum concentrations following oral administration of Methotrexate may be slightly lower than those following I.V. injection.

Methotrexate is actively transported across cell membranes. The drug is widely distributed into body tissues with highest concentrations in the kidneys, gall bladder, spleen, liver and skin. Methotrexate is retained for several weeks in the kidneys and for months in the liver. Sustained serum concentrations and tissue accumulation may result from repeated daily doses. Methotrexate crosses the placental barrier and is distributed into breast milk. Approximately 50% of the drug in the blood is bound to serum proteins.

In one study, Methotrexate had a serum half-life of 2-4 hours following I.M. administration. Following oral doses of 0.06mg/kg or more, the drug had a serum half-life of 2-4 hours, but the serum half-life was reported to be increased to 8-10 hours when oral doses of 0.037mg/kg were given.

Methotrexate does not appear to be appreciably metabolised. The drug is excreted primarily by the kidneys via glomerular filtration and active transport. Small amounts are excreted in the faeces, probably via the bile. Methotrexate has a biphasic excretion pattern. If Methotrexate excretion is impaired accumulation will occur more rapidly in patients with impaired renal function. In addition, simultaneous administration of other weak organic acids such as salicylates may suppress Methotrexate clearance.

6. Pharmaceutical Particulars 6.1 List Of Excipients

Other Constituents

 

 

5 mg/2 ml

25 mg/ml

100 mg/ml

Sodium Chloride

BP

17.2 mg

4.9 mg

None

Sodium Hydroxide

BP

QS

QS

QS

Water for Injections

BP

To 2 ml

To 1 ml

To 1 ml

There is a 5 % manufacturing overage included in the formulation.

6.2 Incompatibilities

Immediate precipitation or turbidity results when combined with certain concentrations of

Droperidol, Heparin Sodium, Metoclopramide Hydrochloride, Ranitidine

Hydrochloride in syringe.

6.3 Shelf Life

5 mg/2 ml and 25 mg/ml – 24 months

100 mg/ ml - 30 months

6.4 Special Precautions For Storage

For the 1g/40ml presentation : Store between 2-8°C. Protect from light.

For all other prersentations: Store below 25°C. Protect from light and freezing.

Unused portions of opened vials must not be stored and should be discarded immediately. Prepared infusions, not used immediately, must be stored at 2-8°C for no longer than 24 hours from the time of preparation.

6.5 Nature And Contents Of Container

Conventional Glass Vials (5 mg/ 2 ml, 50mg/2ml, 250mg/10ml, 500mg/20ml, 1 g/10 ml and 5 g/50 ml):

Type I glass vial, 2ml, 13mm, 1704 rubber closure, aluminium seal with plastic 'flip-off' top in packs of 5 vials.

Type I glass vial, 10ml, 13mm, 1704 rubber closure, aluminium seal with plastic 'flip-off' top in packs of 5 vials.

Type I glass vial, 20ml, 20mm, 1704 rubber closure, aluminium seal with plastic 'flip-off' top in single vial packs.

Type I glass vial, 10ml, 20mm, 1704 rubber closure, aluminium seal with plastic 'flip-off' top in single vial packs.

Type I glass vial, 50ml, 20mm, 1704 rubber closure, aluminium seal with plastic 'flip-off' top in single vial packs.

Onco-TainTM Vials (5 mg/2 ml, 50mg/2ml, 500mg/20ml, 1 g/10 ml and 5 g/50 ml only):

Clear Type I Onco-TainTM vial, 2ml, 13mm, 1704 rubber closure, aluminium seal with plastic 'flip-off' top in packs of 5 vials.

Clear Type I Onco-TainTM vial, 20ml, 20mm, 1704 rubber closure, aluminium seal with plastic 'flip-off' top in single vial packs.

Clear Type I Onco-TainTM vial, 10ml, 20mm, 1704 rubber closure, aluminium seal with plastic 'flip-off' top in single vial packs.

Clear Type I Onco-TainTM vial, 50ml, 20mm, 1704 rubber closure, aluminium seal with plastic 'flip-off' top in single vial packs.

Onco-Vial TM (Shell Glass Vials )(500mg/20ml, 1g/40ml, 1 g/10 ml and 5 g/ 50 ml only):

Clear Type I shell glass vial, 10ml, 15mm, west type 4405/50 rubber closure in single vial packs.

Clear Type I shell glass vial, 50ml, 27mm, west type 4405/50 rubber closure in single vial packs.

Clear Type I shell glass vial, 50ml, 27mm, west type 4416/50 rubber closure in single vial packs.

Not all presentations and pack sizes listed above may be marketed.

6.6 Special Precautions For Disposal And Other Handling

Not applicable.

7. Marketing Authorisation Holder

Faulding Pharmaceuticals Plc

Queensway

Royal Leamington Spa

Warwickshire, CV31 3RW

8. Marketing Authorisation Number(S)

5 mg/2 ml presentation: PL 04515/0013

25 mg/ml presentation: PL 04515/0015

100 mg/ml presentation: PL 04515/0038

9. Date Of First Authorisation/Renewal Of The Authorisation

21st August 1985/11th March 1996

10. Date Of Revision Of The Text

12th July 2000



Address Morton Grove Pharmaceuticals, Inc,



Pronunciation: METH-il-pred-NIS-oh-lone



Pronunciation: a-LOO-min-uhm/mag-NEE-zee-uhm



Generic Name: rizatriptan (RYE za TRIP tan)



Generic Name: ascorbic acid (Oral route)

as-KORE-bik AS-id

Commonly used brand name(s)

In the U.S.

Ascocid C-500 Cecon Cemill 1000 Cemill 500 Cevi-Bid C-Time w/Rose Hips Mega-C One-Gram C Protexin Sunkist Vitamin C

In Canada

Ce-Vi-Sol Revitalose-C-1000 Revitonus C-1000 Yellow Ampule Vitamin C Powder

Available Dosage Forms:

Tablet Powder Powder for Solution Capsule, Liquid Filled Tablet, Chewable Granule Capsule Syrup Powder for Suspension Liquid Solution Tablet, Extended Release Lozenge/Troche Capsule, Extended Release Wafer

Therapeutic Class: Nutritive Agent

Pharmacologic Class: Vitamin C

Uses For Mega-C

Vitamins are compounds that you must have for growth and health. They are needed in small amounts only and are usually available in the foods that you eat. Ascorbic acid, also known as vitamin C, is necessary for wound healing. It is needed for many functions in the body, including helping the body use carbohydrates, fats, and protein. Vitamin C also strengthens blood vessel walls.

Lack of vitamin C can lead to a condition called scurvy, which causes muscle weakness, swollen and bleeding gums, loss of teeth, and bleeding under the skin, as well as tiredness and depression. Wounds also do not heal easily. Your health care professional may treat scurvy by prescribing vitamin C for you.

Some conditions may increase your need for vitamin C. These include:

AIDS (acquired immune deficiency syndrome) Alcoholism Burns Cancer Diarrhea (prolonged) Fever (prolonged) Infection (prolonged) Intestinal diseases Overactive thyroid (hyperthyroidism) Stomach ulcer Stress (continuing) Surgical removal of stomach Tuberculosis

Also, the following groups of people may have a deficiency of vitamin C:

Infants receiving unfortified formulas Smokers Patients using an artificial kidney (on hemodialysis) Patients who undergo surgery Individuals who are exposed to long periods of cold temperatures

Increased need for vitamin C should be determined by your health care professional.

Vitamin C may be used for other conditions as determined by your health care professional.

Claims that vitamin C is effective for preventing senility and the common cold, and for treating asthma, some mental problems, cancer, hardening of the arteries, allergies, eye ulcers, blood clots, gum disease, and pressure sores have not been proven. Although vitamin C is being used to reduce the risk of cardiovascular disease and certain types of cancer, there is not enough information to show that these uses are effective.

Injectable vitamin C is given by or under the supervision of a health care professional. Other forms of vitamin C are available without a prescription.

Once a medicine or dietary supplement has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although these uses are not included in product labeling, vitamin C is used in certain patients with the following medical conditions:

Overdose of iron (to help another drug in decreasing iron levels in the body) Methemoglobinemia (a blood disease) Importance of Diet

For good health, it is important that you eat a balanced and varied diet. Follow carefully any diet program your health care professional may recommend. For your specific dietary vitamin and/or mineral needs, ask your health care professional for a list of appropriate foods. If you think that you are not getting enough vitamins and/or minerals in your diet, you may choose to take a dietary supplement.

Vitamin C is found in various foods, including citrus fruits (oranges, lemons, grapefruit), green vegetables (peppers, broccoli, cabbage), tomatoes, and potatoes. It is best to eat fresh fruits and vegetables whenever possible since they contain the most vitamins. Food processing may destroy some of the vitamins. For example, exposure to air, drying, salting, or cooking (especially in copper pots), mincing of fresh vegetables, or mashing potatoes may reduce the amount of vitamin C in foods. Freezing does not usually cause loss of vitamin C unless foods are stored for a very long time.

Vitamins alone will not take the place of a good diet and will not provide energy. Your body also needs other substances found in food such as protein, minerals, carbohydrates, and fat. Vitamins themselves often cannot work without the presence of other foods.

The daily amount of vitamin C needed is defined in several different ways.

For U.S.— Recommended Dietary Allowances (RDAs) are the amount of vitamins and minerals needed to provide for adequate nutrition in most healthy persons. RDAs for a given nutrient may vary depending on a person's age, sex, and physical condition (e.g., pregnancy). Daily Values (DVs) are used on food and dietary supplement labels to indicate the percent of the recommended daily amount of each nutrient that a serving provides. DV replaces the previous designation of United States Recommended Daily Allowances (USRDAs). For Canada— Recommended Nutrient Intakes (RNIs) are used to determine the amounts of vitamins, minerals, and protein needed to provide adequate nutrition and lessen the risk of chronic disease.

Normal daily recommended intakes for vitamin C are generally defined as follows:

Persons U.S.



Pronunciation: fen-il-EF-rin/skoe-PAHL-ah-meen



Pronunciation: MEL-fa-lan



Pronunciation: METH-uh-dohn



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