Flagyl 200mg Tablets

Each tablet contains 200mg metronidazole.

For a full list of excipients, see section 6.1

Film-coated tablets

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

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).

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.

Adults

400 mg 8 hourly during 24 hours immediately preceding operation followed by postoperative intravenous or rectal administration until the patient is able to take tablets.

Children

7.5 mg/kg 8 hourly.

Treatment of established anaerobic infection:

Adults

800 mg followed by 400 mg 8 hourly.

Children

7.5 mg/kg 8 hourly

Protozoal and other infections:

Known hypersensitivity to metronidazole or any of the excipients.

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.

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 but it has been in wide use for many years without apparent ill consequence. Nevertheless Flagyl, like other medicines, should not 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 rapidly and almost completely absorbed on administration of Flagyl tablets; peak plasma concentrations occur after 20 min to 3 hours.

The half-life of metronidazole is 8.5 ± 2.9 hours. Metronidazole can be used in chronic renal failure; it is rapidly removed from the plasma by dialysis. Metronidazole is excreted in milk but the intake of a suckling infant of a mother receiving normal dosage would be considerably less than the therapeutic dosage for infants.

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

Calcium hydrogen phosphate (E341),

Starch maize,

Povidone K30 (E1201),

Magnesium stearate (E572),

Tablet coat

Pharmacoat 615 (E464),

Macrogol 400 Ph. Eur.

Not applicable

5 years

Store in the original package in order to protect from light.

This medicinal product does not require any special temperature storage conditions.

Flagyl tablets 200 mg are available in aluminium/plastic blisters of 21 tablets and HDPE bottles of 100 and 250 tablets.

Not all pack sizes may be marketed

No special requirements

Winthrop Pharmaceuticals UK Limited

One Onslow Street

Guildford

Surrey

GU1 4YS

United Kingdom

Trading as: Winthrop Pharmaceuticals, PO Box 611, Guildford, Surrey, GU1 4YS

PL 17780/0276

03 January 2007

27 August 2008