Flagyl S 200mg/5ml Oral Suspension

Each 5ml of suspension contains 200mg metronidazole (as the benzoate)

Excipients

This medicinal product contains small amounts of ethanol (alcohol), less than 100mg per 5ml.

For a full list of excipients, see section 6.1

Oral suspension

Flagyl S suspension is a white to cream suspension with a slight yellow tinge and an odour of orange and lemon.

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. Treatment of urogenital trichomonas in the female (trichomonal vaginitis) and in the male.

3. Treatment of all forms of amoebiasis (intestinal and extra-intestinal disease and that of symptomless cyst passers).

4. Treatment of giardiasis.

5. Treatment of acute ulcerative gingivitis (Vincent's).

6. Treatment of anaerobically-infected leg ulcers and pressure sores.

7. Treatment of acute dental infections (e.g. acute pericoronitis and acute apical infections).

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

9. Non specific vaginitis.

Considerations should be given to official guidance on the appropriate use of antibacterial agents.

For oral administration.

Suspension can be diluted with syrup BP.

Dosage is given in terms of metronidazole or metronidazole equivalent.

Treatment of anaerobic infections:

Treatment for seven days should be satisfactory for most patients but, depending on the clinical and bacteriological assessments, the physician might decide to prolong treatment. The tablets or suspension may be given alone or concurrently with other appropriate antibacterial agents.

Adults and children over 10 years - 400 mg orally three times daily.

Children and infants - 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.

Prophylaxis against postoperative infections caused by anaerobic bacteria:

Children < 12 years: 20-30 mg/kg as a single dose given 1-2 hours before surgery

Newborns with a gestation age <40 weeks: 10mg/kg body weight as a single dose before operation

Protozoal and other infections:

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.

Known hypersensitivity to nitroimidazoles, metronidazole or any of the excipients.

Flagyl suspension contains methylhydroxybenzoate and propylhydroxybenzoate which may cause allergic reactions (possibly delayed).

Flagyl suspension contains small amounts of ethanol (alcohol), less than 100mg per 5ml.

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 paresthesia, 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 with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

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.

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.

There is inadequate evidence of the safety of metronidazole in pregnancy. Flagyl 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.

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.

Pharmacotherapeutic code: Antibacterials for systemic us, ATC code: J01X D01

Metronidazole 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.

Metronidazole is rapidly absorbed after oral administration of Flagyl with peak plasma concentrations occur after 20 min to 3 hours.

The elimination half-life of metronidazole is 7 - 8 hours. Metronidazole is excreted in milk but the intake of a suckling infant of a mother receiving normal dose would be considerably less than the therapeutic dosage for infants.

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 other studies were negative.

Liquid sugar granular liquors (sucrose)

Sodium dihydrogen phosphate LC or sodium acid phosphate crystalline

Veegum HV

Methyl hydroxybenzoate (E218)

Propyl hydroxybenzoate (E216)

Ethanol 96% v/v

Lemon No. 1 NA

Oil orange terpenless

Purified water

This medicinal product must not be mixed with other medicinal products except syrup BP for dilution.

3 years

After dilution with syrup BP the shelf life is 14 days.

Store below 25°C. Protect from light.

Flagyl S suspension is available in amber glass bottles containing 50, 100 or 125 ml with either a rolled on pilfer proof aluminium cap and a PVDC emulsion coated wad or a HDPE/polypropylene child resistant cap with a tamper evident band.

Not all pack sizes may be marketed.

No special requirements

Winthrop Pharmaceuticals UK Limited

One Onslow Street

Guildford

Surrey

GU1 4YS

United Kingdom

PL 17780/0275

03 January 2007

11 May 2011

POM