Flagyl-S 200mg/5ml Oral Suspension.

Each 5 ml of Suspension contains Metronidazole Benzoate equivalent to 200 mg of Metronidazole.

For a full list of excipients, see section 6.1.

Oral Suspension.

A white to cream-yellow oral suspension easily redispersible with gentle shaking.

In the treatment of urogenital trichomonaisis.

In the treatment of acute ulcerative gingivitis.

In the treatment of infections due to E. histolytica (including carrier states).

In the treatment of infections due to G. Lamblia (including carrier states).

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

In the treatment of acute dental infections.

In the treatment of chronic pressure sores and ulcers with possible infection due to anaerobes.

In the treatment of non-specific vaginitis.

Oral

Recommended Dosage:

1. Urogential trichomoniasis

Adults and children over 10 years:

600 mg daily in divided doses for 7 days. (Where appropriate the partner should be treated at the same time).

A short two day course of 2 g in two divided doses daily may be used or a single dose of 2 g.

Children:

Aged 7 to 10 years:

300 mg daily in three divided doses.

Aged 3 to 7 years:

200 mg daily in two divided doses.

Aged 1 to 3 years:

150 mg daily in three divided doses. Treatment to continue for 7 days.

2. Acute ulcerative gingivitis

Adults & Children over 10 years:

600 mg daily in divided doses for 3 days.

Children:

Aged 7 to 10 years:

300 mg daily in 3 divided doses for 3 days.

Aged 3 to 7 years:

200 mg daily in 2 divided doses for 3 days.

Aged 1 to 3 years:

150 mg in 3 divided doses for 3 days.

3. Amoebiasis

Adults and children over 10 years:

1200 to 2400 mg daily in three divided doses.

Children:

Aged 7 to 10 years:

600 to 1200 mg daily in 3 divided doses.

Aged 3 to 7 years:

400 to 800 mg daily in 4 divided doses.

Aged 1 to 3 years:

300 to 600 mg daily in 3 divided doses.

Treatment is usually required for five to ten days.

4. Giardiasis

Adults and children over 10 years:

2000 mg once daily for 3 days.

Children:

Aged 7 to 10 years:

1000 mg once daily for 3 days.

Aged 3 to 7 years:

600 mg once daily for 3 days.

Aged 1 to 3 years:

400 to 500 mg once daily for 3 days.

5. Anaerobic infections

Treatment

Adults:

800 mg followed by 400 mg 8 hourly.

Children:

7.5 mg/kg 8 hourly.

Treatment should be discontinued as indicated by the clinical and bacteriological assessment by the clinician, but seven days should generally be sufficient.

Prophylaxis against Anaerobic infections:

Adults:

400 mg at 8 hourly intervals during the 24 hours immediately preceding operation, followed post operatively by intravenous or rectal administration until oral dosing can be resumed.

Children:

7.5mg/kg 8 hourly.

6. Dental Infections

The usual total daily dose is 600 to 800 mg in divided doses. Treatment should generally be continued for 3 to 7 days.

7. Chronic pressure sores and ulcers

Adults:

1200 mg daily in 3 divided doses.

8. Non-specific Vaginitis

Adults and children over 10 years:

A single dose of 2g may be used or 400 mg twice daily for 7 days.

Adjustment of dosage does not appear necessary in patients with renal impairment.

In the case of children whose weights are below those usual for their age, or of infants below 10 kg in weight, dosage of metronidazole should be reduced proportionately.

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

Elderly:

Caution is advised particularly at high doses. No information is available on modification of dosage.

Hepatic Encephalopathy

Daily dosage should be reduced to one third and may be given once daily (see precautions).

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

Use in patients with known hypersensitivity to metronidazole.

If prolonged therapy is required, the physician should bear in mind the possibility of peripheral neuropathy or leucopenia. Both effects are usually reversible. It is recommended that haematological tests be carried out regularly and that patients should be monitored for adverse reactions such as peripheral or central neuropathy (such as paraesthesia, ataxia, dizziness, convulsive seizures).

High dosage regimens have been associated with transient epileptiform seizures. Caution is required in patients with active disease of the central nervous system except for brain abscess.

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

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

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

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.

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

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

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).

This medicinal product contains small amounts of ethanol (alcohol), less than 100mg per 5ml dose.

Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

Potentiation of the anticoagulant effect and increased hemorrhagic risk caused by decreased hepatic catabolism. In case of coadministration, prothrombin time should be more frequently monitored and anticoagulant therapy adjusted during treatment with metronidazole.

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).

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

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. Plasma levels of lithium may be increased by 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.

Phenytoin or Phenobarbital: increased elimination of metronidazole resulting in reduced plasma levels. A similar effect may occur with other drugs which induce hepatic microsomal enzymes.

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

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

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. Its effects on foetal organogenesis are not known. 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, malaise, diarrhoea.

- 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, paraesthesia

- 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 12g 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 cases of suspected massive overdosage, a symptomatic and supportive treatment should be instituted.

Metronidazole has antiprotozoal and antibacterial actions including activity against anaerobic bacteria and entamoeba histolytica.

A nitroimidazole derivative well absorbed and widely distributed in the body. It is metabolised by hepatic acid oxidation, hydroxylation and glucuronidation and excreted in urine and faeces with a T½ of about 6-10 hours.

None

Not applicable.

Unopened: 3 years.

After opening discard any unused suspension after 28 days.

Flagyl-S Suspension may be diluted, if necessary, with Syrup BP. The diluted suspension has a shelf life of 14 days.

Do not store above 25°C. Store in the original container to protect from light.

This product is supplied in amber, glass bottles with a pilfer proof aluminium cap with a polyvinylidene chloride liner or a polypropylene child proof cap with a polyethylene liner, containing 50, 100 or 125ml suspension.

Not all pack sizes may be marketed.

No special requirements.

sanofi-aventis Ireland Ltd.

Citywest Business Campus,

Dublin 24.

PA 540/100/1

1^st April 1977 / 1^st April 2007.

February 2010.