1. Name Of The Medicinal Product
Flagyl 200mg Tablets
2. Qualitative And Quantitative Composition
Each tablet contains 200mg metronidazole.
For a full list of excipients, see section 6.1
3. Pharmaceutical Form
Film-coated tablets
White to off-white, circular biconvex, film coated tablets impressed 'FLAGYL 200' on one face, plain reverse.
4. Clinical Particulars
4.1 Therapeutic 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.
Flagyl is indicated in adults and children for the following indications:
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).
Considerations should be given to official guidance on the appropriate use of antibacterial agents.
4.2 Posology And Method Of Administration
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.
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
Children < 12 years: 20-30mg/kg as a single dose given 1-2 hours before surgeryNewborns with a gestation age < 40 weeks: 10mg/kg body weight as a single dose before operation
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.
Treatment of established anaerobic infection:
Adults
800 mg followed by 400 mg 8 hourly.
Children
Children > 8 weeks to 12 years of age: The usual daily dose is 20-30mg/kg/day as a single dose or divided into 7.5mg/kg every 8 hours. The daily dose may be increased to 40mg/kg, depending on the severity of the infection. Duration of treatment is usually 7 days.
Children < 8 weeks of age: 15mg/kg as a single dose daily or divided into 7.5mg/kg every 12 hours. In newborns with a gestation age < 40 weeks, accumulation of metronidazole can occur during the first week of life, therefore the concentrations of metronidazole in serum should preferable be monitored after a few days therapy.
Protozoal and other infections:
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Eradication of Helicobacter pylori in paediatric patients:
As a part of a combination therapy, 20mg/kg/day not to exceed 500mg twice daily for 7-14 days. Official guidelines should be consulted before initiating therapy.
4.3 Contraindications
Known hypersensitivity to nitroimidazoles, metronidazole or any of the excipients.
4.4 Special Warnings And Precautions For Use
Regular clinical and laboratory monitoring (especially leucocyte count) are advised if administration of Flagyl for more than 10 days is considered to be necessary and patients should be monitored for adverse reactions such as peripheral or central neuropathy (such as paraesthesia, ataxia, dizziness, convulsive seizures).
Metronidazole should be used with caution in patients with active or chronic severe peripheral and central nervous system disease due to the risk of neurological aggravation.
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 warned that metronidazole may darken urine.
Due to inadequate evidence on the mutagenicity risk in humans (see section 5.3), the use of flagyl for longer treatment than usually required should be carefully considered.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
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. Psychotic reactions have been reported in patients who were using metronidazole and disulfiram concurrently.
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 or phenytoin 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.
4.6 Pregnancy And Lactation
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.
4.7 Effects On Ability To Drive And Use Machines
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.
4.8 Undesirable Effects
The frequency of adverse events listed below is defined using the following convention:
very common (
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, fever. | |
Metabolism and nutrition disorders: | |
Not known: anorexia. | |
Psychiatric disorders: | |
Very rare: psychotic disorders, including confusion and hallucinations. | |
Not known: depressed mood | |
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: vision disorders such as diplopia and myopia, which, in most cases, is transient. | |
Gastrointestinal 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, flushing | |
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). |
4.9 Overdose
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 overdose, symptomatic and supportive treatment should be instituted.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
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.
5.2 Pharmacokinetic Properties
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.
5.3 Preclinical Safety Data
Metronidazole has been shown to be carcinogenic in the mouse and in the rat following chronic oral administration however similar studies in the hamster have given negative results. Epidemiological studies have provided no clear evidence of an 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 or humans in vivo, there was inadequate evidence of a mutagenic effect of metronidazole, with some studies reporting mutagenic effects, while others studies were negative.
6. Pharmaceutical Particulars
6.1 List Of Excipients
Calcium hydrogen phosphate (E341),
Starch maize,
Povidone K30 (E1201),
Magnesium stearate (E572),
Tablet coat
Pharmacoat 615 (E464),
Macrogol 400 Ph. Eur.
6.2 Incompatibilities
Not applicable
6.3 Shelf Life
5 years
6.4 Special Precautions For Storage
Store in the original package in order to protect from light.
This medicinal product does not require any special temperature storage conditions.
6.5 Nature And Contents Of Container
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
6.6 Special Precautions For Disposal And Other Handling
No special requirements
7. Marketing Authorisation Holder
Winthrop Pharmaceuticals UK Limited
One Onslow Street
Guildford
Surrey
GU1 4YS
United Kingdom
8. Marketing Authorisation Number(S)
PL 17780/0276
9. Date Of First Authorisation/Renewal Of The Authorisation
03 January 2007
10. Date Of Revision Of The Text
16.03.2011
LEGAL CATEGORY
POM
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