Flagyl 500mg/100ml Solution for Infusion

Flagyl 500mg/100ml Solution for Infusion – Minibag Plus

Each ml of solution for infusion contains 5mg metronidazole.

Each 100ml of solution for infusion contains 500mg metronidazole.

Excipients:

Each ml of solution for infusion contains 0.134 mmol (3.07 mg ) sodium

Each 100ml of solution for infusion contains 13.365 mmol (307 mg) sodium.

For a full list of excipients, see section 6.1

Solution for Infusion

A clean, bright, pale yellow sterile isotonic solution for intravenous infusion.

Flagyl is indicated in the prophylaxis and treatment of infections in which anaerobic bacteria have been identified or are suspected to be the cause.

Flagyl is active against a wide range of pathogenic micro-organisms notably species of Bacteroides, Fusobacteria, Clostridia, Eubacteria, anaerobic cocci and Gardnerella vaginalis.

It is indicated in:

1. The prevention of postoperative infections due to anaerobic bacteria, particularly species of Bacteroides and anaerobic Streptococci.

2. The treatment of septicaemia, bacteraemia, peritonitis, brain abscess, necrotising pneumonia, osteomyelitis, puerperal sepsis, pelvic abscess, pelvic cellulitis, and post-operative wound infections from which pathogenic anaerobes have been isolated.

Flagyl infusion should be infused intravenously at an approximate rate of 5 ml/min. Oral medication should be substituted as soon as feasible.

Anaerobic Infections: Treatment for seven days should be satisfactory for most patients but, depending upon clinical and bacteriological assessments, the physician might decide to prolong treatment e.g. for the eradication of infection from sites which cannot be drained or are liable to endogenous recontamination by anaerobic pathogens from the gut, oropharynx or genital tract.

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

Adults

500mg shortly before operation, repeated 8 hourly. Oral doses of 200 mg or 400 mg 8 hourly to be started as soon as feasible.

Children

7.5 mg/kg (1.5 ml/kg) 8 hourly.

Treatment of established anaerobic infections: Intravenous route is to be used initially if patient's symptoms preclude oral therapy.

Adults

500 mg 8 hourly.

Children

7.5 mg/kg 8 hourly.

Elderly

Caution is advised in the elderly. Particularly at high doses although there is limited information available on modification of dosage.

Known hypersensitivity to metronidazole or any of the excipients.

This medicinal product contains 13.365 mmol (307 mg) sodium per 100 ml of solution. To be taken into consideration by patients on a controlled sodium diet.

Metronidazole has no direct activity against aerobic or facultative anaerobic bacteria.

Regular clinical and laboratory monitoring are advised if administration of Flagyl for more than 10 days is considered to be necessary.

There is a possibility that after Trichomonas vaginalis has been eliminated a gonococcal infection might persist.

The elimination half-life of metronidazole remains unchanged in the presence of renal failure. Therefore the dosage of metronidazole needs no reduction. Such patients however retain the metabolites of metronidazole. The clinical significance of this is not known at present.

In patients undergoing haemodialysis metronidazole and metabolites are efficiently removed during an eight hour period of dialysis. Metronidazole should therefore be re-administered immediately after haemodialysis.

No routine adjustment in the dosage of Flagyl need be made in patients with renal failure undergoing intermittent peritoneal dialysis (IDP) or continuous ambulatory peritoneal dialysis (CAPD).

Metronidazole is mainly metabolised by hepatic oxidation. Substantial impairment of metronidazole clearance may occur in the presence of advanced hepatic insufficiency. Significant cumulation may occur in patients with hepatic encephalopathy and the resulting high plasma concentrations of metronidazole may contribute to the symptoms of the encephalopathy. Flagyl should therefore, be administered with caution to patients with hepatic encephalopathy. The daily dosage should be reduced to one third and may be administered once daily.

Aspartate amino transferase assays may give spuriously low values in patients being treated with metronidzole depending on the method used.

Flagyl should be used with caution in patients with active disease of the CNS.

Cefuroxime is physically and chemically compatible with Flagyl. The following drugs have been shown to be physically compatible in terms of pH and appearance with Flagylinfusion over the normal period of administration, although there is no evidence of chemical stability: amikacin sulphate, ampicillin sodium, carbenicillin sodium, cephazolin sodium, cefotaxime sodium, cephalothin sodium, chloramphenicol sodium succinate, clindamycin phosphate, gentamicin sulphate, hydrocortisone sodium succinate, latamoxef disodium, netilmicin sulphate and tobramycin sulphate. In patients maintained on intravenous fluids, Flagyl infusionmay be diluted with appropriate volumes of normal saline, dextrose-saline, dextrose 5% w/v or potassium chloride infusions (20 and 40 mmol/litre). Apart from the above, Flagyl should on no account be mixed with any other substance.

Patients should be advised not to take alcohol during metronidazole therapy and for at least 48 hours afterwards because of the possibility of a disulfiram-like (antabuse effect) reaction.

Some potentiation of anticoagulant therapy has been reported when metronidazole has been used with the warfarin type oral anticoagulants. Dosage of the latter may require reducing. Prothrombin times should be monitored. There is no interaction with heparin.

Lithium retention 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 concentrations of lithium, creatinine and electrolytes should be monitored in patients under treatment with lithium while they receive metronidazole.

Patients receiving phenobarbital metabolise metronidazole at a much greater rate than normally, reducing the half-life to approximately 3 hours.

Metronidazole reduces the clearance of 5 fluorouracil and can therefore result in increased toxicity of 5 fluorouracil.

Patients receiving ciclosporin are at risk of elevated ciclosporin serum levels. Serum ciclosporin and serum creatinine should be closely monitored when coadministration is necessary.

Plasma levels of busulfan may be increased by metronidazole which may lead to severe busulfan toxicity.

There is inadequate evidence of the safety of metronidazole in pregnancy. Flagyl should not therefore be given during pregnancy or during lactation unless the physician considers it essential; in these circumstances the short, high-dosage regimens are not recommended.

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

The frequency of adverse events listed below is defined using the following convention:

very common ( 1/10); common ( 1/100 to < 1/10); uncommon ( 1/1,000 to < 1/100); rare ( 1/10,000 to < 1/1,000); very rare (< 1/10,000), not known (cannot be estimated from the available data).

Serious adverse reactions occur rarely with standard recommended regimens. Clinicians who contemplate continuous therapy for the relief of chronic conditions, for periods longer than those recommended, are advised to consider the possible therapeutic benefit against the risk of peripheral neuropathy.

Blood and lymphatic system disorders:

Very rare: agranulocytosis, neutropenia, thrombocytopenia, pancytopenia

Not known: leucopenia.

Immune system disorders:

Rare: anaphylaxis

Not known: angiodema, urticaria.

Metabolism and nutrition disorders:

Not known: anorexia.

Psychiatric disorders:

Very rare: psychotic disorders, including hallucinations.

Nervous system disorders:

Very rare:

• encephalopathy (eg. confusion, fever, headache, hallucinations, paralysis, light sensitivity, disturbances in sight and movement, stiff neck) and subacute cerebellar syndrome (eg. ataxia, dysathria, gait impairment, nystagmus and tremor) which may resolve on discontinuation of the drug.

• drowsiness, dizziness, convulsions, headaches

Not known: during intensive and/or prolonged metronidazole therapy, peripheral sensory neuropathy or transient epileptiform seizures have been reported. In most cases neuropathy disappeared after treatment was stopped or when dosage was reduced.

Eye disorders:

Very rare: diplopia, myopia.

Gastrointestinal disorders:

Not known: taste disorders, oral mucositis, furred tongue, nausea, vomiting, gastro-intestinal disturbances.

Hepatobiliary disorders:

Very rare: abnormal liver function tests, cholestatic hepatitis, jaundice and pancreatitis which is reversible on drug withdrawal.

Skin and subcutaneous tissue disorders:

Very rare: skin rashes, pustular eruptions, pruritis

Not known: erythema multiforme.

Musculoskeletal, connective tissue and bone disorders:

Very rare: myalgia, arthralgia.

Renal and urinary disorders:

Very rare: darkening of urine (due to metronidazole metabolite).

There is no specific treatment for gross overdosage of Flagyl.

Pharmacotherapeutic group: Antibacterials for systemic use, ATC code: J01X D01.

Metronidazole has antiprotozoal and antibacterial actions and is effective against Trichomonas vaginalis and other protozoa including Entamoeba histolytica and Giardia lamblia and against anaerobic bacteria.

Metronidazole is widely distributed in body tissues after injection. At least half the dose is excreted in the urine as metronidazole and its metabolites, including an acid oxidation product, a hydroxy derivative and glucuronide. Metronidazole diffuses across the placenta, and is found in breast milk of nursing mothers in concentrations equivalent to those in serum.

10% of the dose is bound in plasma.

Clearance: 1.3 + 0.3 ml/min/kg.

Volume of distribution: 1.1 + 0.4 litres/kg.

Half-life: 8.5 + 2.9 hours.

Effective concentration: 3-6 micrograms/ml.

There are no preclinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

Sodium phosphate

Citric acid anhydrous

Sodium chloride

Water for injections

Flagyl infusionshould not be mixed with cefamandole nafate, cefoxitin sodium, dextrose 10% w/v, compound sodium lactate injection, penicillin G potassium.

Glass bottles containing 100 ml -3 years.

Viaflex minibags containing 100 ml - 2 years

100 ml bottle: store below 30°C, protect from light.

100 ml Viaflex minibags: store below 25°C, protect from light.

Flagyl infusion 0.5% w/v (100 ml) is available in type I glass or type II glass DIN bottles closed with a chlorobutyl or bromobutyl rubber plug.

Flagyl infusion0.5% w/v (100 ml) is available in Viaflex minibags.

Flagyl infusion- Minibag Plus 0.5% w/v (100 ml) is available in Viaflex minibags incorporating a combination device.

The Viaflex containers are for single use only. Discard any unused portion. Do not reconnect partially used containers.

May and Baker Limited

trading as

May & Baker or Rorer Pharmaceuticals or Rhône-Poulenc Rorer or Pharmuka or Theraplix or APS or Berk Pharmaceuticals

RPR House

50 Kings Hill Avenue

Kings Hill

West Malling

Kent ME19 4AH

PL 00012/0107

24 September 1996

14 May 2008

POM