Flagyl Suppositories 0.5g.

Each suppository contains 0.5g (500mg) of Metronidazole.

For a full list of excipients, see section 6.1.

Suppository.

Cream coloured, smooth, torpedo-shaped suppository.

In the prevention and treatment of infections due to anaerobic bacteria, particularly species of Bacteroides, anaerobic Streptococci, Fusobacteria, Clostridia, etc.

Rectal.

Recommended Dosage:

Adults:

1g 8 hourly. Substitute oral medication as early as possible. If rectal administration is prolonged beyond 3 days reduce dose to 1g 12 hourly for remainder of course.

Children:

7.5 mg/kg 8 hourly.

Prophylaxis against anaerobic infection-chiefly in the context of abdominal (especially colorectal) and gynaecological surgery:

Adults:

1g 8 hourly.

Children one half or a quarter of a 500mg suppository 8 hourly.

Metronidazole should be used with caution in patients with active or chronic severe peripheral and central nervous system diseases due to the risk of neurological aggravation.

Use in patients known to be hypersensitive to metronidazole.

1. If prolonged therapy is required, the physician should bear in mind the possibility of peripheral neuropathy or leucopenia. Both effects are usually reversible. High dosage regimes have been associated with transient epileptiform seizures. Caution is required in patients with active disease of the central nervous system except for brain abscess.

2. Metronidazole and a metabolite have been shown to be mutagenic in some tests with non-mammalian cells.

3. Intensive or prolonged metronidazole therapy should be conducted only under conditions of close surveillance for clinical and biological effects and under specialist direction.

4. Metronidazole is removed during haemodialysis and should be administered after the procedure is finished.

5. Metronidazole is mainly metabolised by hepatic oxidation. Substantial impairment of metronidazole clearance may occur in the presence of advanced hepatic insufficiency. The risk/benefit using metronidazole to treat trichomoniasis in such patients should be carefully considered.

6. Flagyl should be administered with caution to patients with hepatic encephalopathy.

7. Patients should be warned that metronidazole may darken urine (due to metronidazole metabolite).

8. Patients should be advised not to take alcohol during metronidazole therapy and for at least 48 hours afterwards (see section 4.5 Interaction with other medicinal products and other forms of interaction).

1. Potentiation of coumarin anticoagulant effects may occur with metronidazole and anticoagulant activity should be carefully monitored during concurrent therapy.

2. Patients should be advised not to take alcohol, (or drugs containing alcohol) during metronidazole therapy and for at least 48 hours afterwards because of a disulfiram-like (antabuse effect) reaction (flushing, vomiting, tachycardia).

3. Disulfiram: psychotic reactions have been reported in patients who were using metronidazole and disulfiram concurrently.

4. Lithium retention observed by increased plasma lithium levels, accompanied by evidence of possible renal damage has been reported in patients treated simultaneously with lithium and metronidazole. Lithium treatment should be tapered or withdrawn before administering metronidazole. Plasma concentration of lithium, creatinine and electrolytes should be monitored in patients under treatment with lithium while they receive metronidazole.

5. Cyclosporin: risk of elevation of the cyclosporin serum levels. Serum cyclosporin and serum creatinine should be closely monitored when coadministration is necessary.

6. 5-Fluorouracil: reduced clearance of 5-fluorouracil resulting in increased toxicity of 5-fluorouracil.

7. Phenytoin or phenobarbital: increased elimination of metronidazole resulting in reduced plasma levels.

8. Busulfan: Plasma levels of busulfan may be increased by metronidazole, which may lead to severe busulfan toxicity.

Metronidazole should only be used during pregnancy or lactation following careful eva luation and only if considered essential by the physician. If used, high dosage regimens should be avoided. The drug crosses the placenta and is excreted in breast milk in which concentrations equal those in serum. Unnecessary exposure to the drug should be avoided.

Patients should be warned about the potential for confusion, dizziness, hallucinations, convulsions or transient visual disorders, and advised not to drive or operate machinery if these symptoms occur.

• Gastrointestinal effects

- epigastric pain, nausea, vomiting, diarrhoea.

- Glossitis, oral mucositis, taste disorders, dry mouth, anorexia.

- exceptional and reversible cases of pancreatitis.

• Hypersensitivity reactions

- rash, pruritus, flushing, urticaria.

- fever, angioedema, exceptional anaphylactic shocks.

- very rare pustular eruptions.

• Peripheral and central nervous system

- peripheral sensory neuropathy.

- headache, convulsions, dizziness,

- very rare reports of encephalopathy (e.g. confusion) and subacute cerebellar syndrome (e.g. ataxia, dysathria, gait impairment, nystagmus and tremor) which may resolve with discontinuation of the drug.

• Psychiatric disorders

- psychotic disorders including confusion, hallucinations

- depressed mood

• Vision disorders

transient vision disorders such as diplopia, myopia

• Haematology

- very rare cases of agranulocytosis, neutropenia and thrombocytopenia have been reported.

• Liver

- very rare cases of reversible abnormal liver function tests and cholestatic hepatitis sometimes with jaundice have been reported.

Single oral doses of metronidazole, up to 12 g have been reported in suicide attempts and accidental overdoses. Symptoms were limited to vomiting, ataxia and slight disorientation.

There is no specific antidote for metronidazole overdosage. In case of suspected massive overdosage, a symptomatic and supportive treatment should be instituted.

Flagyl - the drug has antiprotozoal and antibacterial actions including activity against anaerobic bacteria, entamoeba histolytica.

A nitroimidazole derivative well absorbed and widely distributed in the body. It is metabolised by acid oxidation, hydroxylation and glucuronidation and excreted in urine and faeces with a T½ of about 7-8 hours.

Metronidazole has been shown to be carcinogenic in the mouse and in the rat. However, similar studies in the hamster have given negative results and extensive human epidemiological studies have provided no evidence of increased carcinogenic risk in humans. Metronidazole has been shown to be mutagenic in bacteria in vitro. In studies conducted in mammalian cells in vitro as well as in rodent and in humans in vivo, there was inadequate evidence of mutagenic effects.

Therefore, the use of Flagyl for longer treatment than usually required should be carefully weighed. (See “Warnings and Precautions”).

Not applicable.

3 years.

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

Performed PVC/polyethylene laminates.

Moulded plaguettes of cellulose acetate, plasticized with approximately 22% diethylphthalate/triphenylphosphate sealed with heat using glycerol triacetate adhesive.

Pack size: boxes 10 x 500g suppositories.

No special requirements

sanofi-aventis Ireland Ltd.

Citywest Business Campus

Dublin 24.

PA 540/100/6

30^th September 1977/30^th September 2007

August 2009.