Flagyl 0.5%w/v Solution for Infusion in Viaflex Container.

Each infusion bag contains 500mg/100ml of metronidazole. (5mg/ml).

For a full list of excipients, see section 6.1.

Solution for infusion (infusion).

A clear pale yellow sterile solution.

In the treatment of severe infections due to anaerobic bacteria, particularly species of Bacteroides, anaerobic Streptococci, etc., and for prophylaxis against such infections, in patients for whom oral medication is not practical.

Intravenous.

Recommended Dosage:

Treatment

Prevention

Infusion should be at the rate of 5ml per minute for treatment. The intravenous route should be discontinued as soon as feasible with substitution or oral medication, (in adults 400mg twice daily – in children 7.5mg/kg b.w. for treatment and 3.7 to 7.5 mg/kg b.w. for prevention.

Children under 10 years: 7.5 mg / kg b.w. immediately before, during and after operation, repeated eight hourly thereafter.

In the case of children whose weights are below those usual for their age, or for 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 dose.

The preparations may be diluted if necessary using only those solution stated in the manufacturer's literature. These include normal saline, dextrose/saline, dextrose 5% w/v or potassium chloride injections 20mmol and 40 mmol.

Metronidazole should be used in 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.

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.

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 in caution to people 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 0.31g of sodium per 100ml dose. To be taken into consideration by patients on a controlled sodium diet.

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.

Flagyl Injection should on no account be administered concurrently mixed with any other substances except: amikacin sulphate, ampicillin sodium, carbenicillin sodium, cephazolin sodium, cefotaxime sodium, cerfuroxime sodium, cephalothin sodium, chloramphenicol sodium succinate, clindamycin phosphate, gentamycin sulphate, hydrocortisone sodium succinate, latamoxef disodium netilmicin sulphate and tobramycin sulphate.

Ampicillin sodium, cephalothin sodium and hydrocortisone sodium succinate should be added cautiously to Flagyl solution. The following solutions are incompatible with Flagyl solution: Cefamandole nafate, cefoxitin sodium, dextrose 10% w/v, compound sodium lactate injection and penicillin G. potassium.

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 include 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, 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.

- 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.

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

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 T_1/2 of about 8 hours. Metronidazole is excreted in milk but the intake of a suckling infant of a mother receiving normal dosage would be consideralbly less than the therapeutic dosage for infants.

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 epidermiological 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”).

Disodium phosphate dodecahydrate (E139) (for pH adjustment)

Citric Acid monohydrate (E330) (for pH adjustment)

Sodium Chloride

Water for Injections

This medicinal product must not be mixed with other medicinal products except those mentioned in section 4.2.

Unopened: 2 years.

Once opened: The product should be used immediately after opening. Discard any unused solution.

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

Flagyl Viaflex 100ml is marked in boxes containing a clear, collapsible PVC infusion bag (viaflex) which may contain an integral combination device, effectively sealed.

This is a single dose container, discard any unused solution.

sanofi-aventis Ireland Ltd.

Citywest Business Campus,

Dublin 24.

PA 540/100/3.

19^th April 1982 / 19^th April 2007.

August 2009.