Drug Class Description
Amoebicides.

Generic Name
Metronidazole - amoebic infections

Drug Description
Each tablet contains 200mg metronidazole.

Presentation
Film-coated tabletsWhite to off-white, circular biconvex, film coated tablets impressed 'FLAGYL 200' on one face, plain reverse.

Indications
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 also active against Trichomonas, Entamoeba histolytica, Giardia lamblia and Balantidium coli. It is indicated in: 1. The prevention of post-operative 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.3. Urogenital trichomoniasis in the female (trichomonal vaginitis) and in the male.4. Bacterial vaginosis (also known as non-specific vaginitis, anaerobic vaginosis or Gardnerella vaginitis).5. All forms of amoebiasis (intestinal and extra-intestinal disease and that of symptomless cyst passers).6. Giardiasis.7. Acute ulcerative gingivitis.8. Anaerobically-infected leg ulcers and pressure sores.9. Acute dental infections (e.g. acute pericoronitis and acute apical infections).

Adult Dosage
Oral route of administration.Flagyl tablets should be swallowed with water (not chewed). It is recommended that the tablets be taken during or after a meal.Anaerobic infections: The duration of a course of Flagyl treatment is about 7 days but it will depend upon the seriousness of the patient's condition as assessed clinically and bacteriologically.Prophylaxis against anaerobic infection: Chiefly in the context of abdominal (especially colorectal) and gynaecological surgery.Adults400 mg 8 hourly during 24 hours immediately preceding operation followed by postoperative intravenous or rectal administration until the patient is able to take tablets.Children7.5 mg/kg 8 hourly.Treatment of established anaerobic infection:Adults800 mg followed by 400 mg 8 hourly.Children7.5 mg/kg 8 hourlyProtozoal and other infections:Dosage is given in terms of metronidazole or metronidazole equivalentDuration of dosage inAdults and children overChildrendays10 years7 to 10 years3 to 7 years1 to 3 yearsUrogenital trichomoniasisWhere re-infectionis likely, in adultsthe consort should7or200 mg three times dailyor400 mg twicedaily100 mg three times daily100 mg twice daily50 mg three times dailyreceive a similar course of treatment concurrently2or800 mg in the morning and 1,200 mg in the evening2.0 g as a single doseBacterialvaginosis7or400 mg twice daily12.0g as a single doseAmoebiasis(a) Invasive intestinal disease in susceptible subjects5800 mg three times daily400 mg three times daily200 mg four times daily200 mg three times daily(b) Intestinal disease in less susceptible subjects and chronic amoebic hepatitis5-10400 mg threetimes daily200 mg threetimes daily100 mg fourtimes daily100 mg threetimes daily(c) Amoebic liver abscess also other forms of extra-intestinal amoebiasis5400 mg threetimes daily200 mg threetimes daily100 mg fourtimes daily100 mg threetimes daily(d) Symptomless cyst passers5-10400-800 mg three times daily200-400 mg three times daily100-200 mg four times daily100-200 mg three times dailyGiardiasis32.0 g once daily1.0 g once daily600-800 mg once daily500 mg once dailyDosage is given in terms of metronidazole or metronidazole equivalentDuration of dosage inAdults and children overChildrendays10 years7 to 10 years3 to 7 years1 to 3 yearsAcute ulcerative gingivitis3200 mg three times daily100 mg three times daily100 mg twice daily50 mg three times dailyAcute dental infections3-7200 mg three times dailyLeg ulcers and pressure sores7400 mg three times dailyChildren and infants weighing less than 10 kg should receive proportionally smaller dosages.Elderly: Flagyl is well tolerated by the elderly but a pharmacokinetic study suggests cautious use of high dosage regimens in this age group.

Child Dosage
See data sheet.

Contra Indications
Known hypersensitivity to metronidazole or any of the excipients.

Special Precautions
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. The dosage of metronidazole therefore 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.

Interactions
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.

Adverse Reactions
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, pancytopeniaNot known: leucopenia.Immune system disorders:Rare: anaphylaxisNot known: angiodema, urticaria, fever.Metabolism and nutrition disorders:Not known: anorexia.Psychiatric disorders:Very rare: psychotic disorders, including confusion and hallucinations.Not known: depressed moodNervous 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, headachesNot 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.• aseptic meningitisEye disorders:Very rare: vision disorders such as diplopia and myopia, which, in most cases, is transient.Not Known: optic neuropathy/neuritisGastrointestinal disorders:Not known: taste disorders, oral mucositis, furred tongue, nausea, vomiting, gastro-intestinal disturbances such as epigastric pain and diarrhoea.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, flushingNot 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).

Manufacturer
Winthrop Pharmaceuticals UK Ltd

Drug Availability
(POM)

Updated
23 November 2011