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.

Flagyl is indicated in adults and children for the following indications:

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.

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

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

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

Children < 12 years: 20-30mg/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

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.

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

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.

Bacterial vaginosis:

Adolescents: 400mg twice daily for 5-7 days or 2000mg as a single dose.

Urogenital trichomoniasis:

Adults and adolescents: 2000mg as a single dose or 200mg 3 times daily for 7 days or 400mg twice daily for 5-7 days

Children < 10 years: 40mg/kg orally as a single dose or 15-30 mg/kg/day divided in 2-3 doses for 7 days; not to exceed 2000mg/dose

Giardiasis:

> 10 years: 2000mg once daily for 3 days, or 400mg three times daily for 5 days, or 500mg twice daily for 7 to 10 days

Children 7 to 10 years: 1000mg once daily for 3 days

Children 3 to 7 years: 600 to 800mg once daily for 3 days

Children 1 to 3 years: 500mg once daily for 3 days

Alternatively, as expressed in mg per kg of body weight: 15-40mg/kg/day divided in 2-3 doses.

Amoebiasis:

> 10 years: 400 to 800mg 3 times daily for 5-10 days

Children 7 to 10 years: 200 to 400mg 3 times daily for 5-10 days

Children 3 to 7 years: 100 to 200mg 4 times daily for 5-10 days

Children 1 to 3 years: 100 to 200mg 3 times daily for 5-10 days

Alternatively, doses may be expressed by body weight: 35 to 50mg/kg daily in 3 divided doses for 5 to 10 days, not to exceed 2400mg/day

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

Elderly

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

Known hypersensitivity to nitroimidazoles, 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 (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. 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.

Patients should be warned that metronidazole may darken urine.

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 Flagyl infusion 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 infusion may 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.

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 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.

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 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.

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.

Sodium phosphate

Citric acid anhydrous

Sodium chloride

Water for injections

Flagyl infusion should 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 infusion 0.5% 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.

Winthrop Pharmaceuticals UK Limited

One Onslow Street

Guildford

Surrey

GU1 4YS

United Kingdom

PL 17780/0515

11 January 2010

11 May 2011

POM