METRONIDAZOLE

Posology Anaerobic infections:

The duration of a course of Metronidazole Tablets 200mg 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: 400mg 8-hourly during 24 hours immediately preceding operation followed by postoperative intravenous or rectal administration until the patient is able to take the tablets.

Children: < 12 years: 20-30mg/kg as a single dose given 1-2 hours before surgery. Newborns with a gestation age of < 40 weeks: 10mg/kg body weight as a single dose before operation.

Treatment of established anaerobic infection:

Adults: 800mg followed by 400mg 8-hourly. 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. 5mg/kg every 12hours. In newborns with a gestation < 40 weeks, accumulation of metronidazole can occur during the first week of life, therefore the concentrations of metronidazole in serum should preferably be monitored after a few days therapy.

Protozoal and other infections Dosage is given in terms of metronidazole or metronidazole equivalent ChildrenDuration of dosage in days Adults and children over 10 years 7 to 10 years 3 to 7 years 1 to 3 years Urogenital Trichomoniasis Where infection is likely in adults the consort should receive similar course of treatment concurrently 7 or 5-7 2000 mg as a single dose or 200 mg three times daily or 400 mg twice daily 40 mg/kg orally as a single dose or 15-30 mg/kg/day divided in 2-3 doses; not to exceed 2000 mg/day Bacterial vaginosis 5-7 or 400 mg twice daily 1 2000 mg as a single dose Amoebiasis (a) Invasive intestinal disease in susceptible subjects 5 800 mg three times daily 400 mg three daily mg times 200 mg four daily mg times 200 mg three times daily (b) Intestinal disease in less susceptible subjects and chronic amoebic hepatitis 5-10 400 mg three times daily 200 mg three times daily 100 mg four times daily 100 mg Three times daily (c) Amoebic liver abscess also other forms of extra- intestinal amoebiasis 5 400 mg three times daily 200 mg three times daily 100 mg four times daily 100 mg Three times daily (d) Symptomless cyst passers 5-10 400-800 mg three times daily 200-400 mg three times daily 100-200 mg four times daily 100-200 mg three times daily Alternatively, doses may be expressed by body weight 35 to 50 mg/kg daily in 3 divided doses for 5 to 10 days, not to exceed 2400 mg/day Giardiasis 3 2000 mg once daily or 1000 mg once daily 600-800 mg once daily 500 mg once daily 5 400 mg three times daily or 7-10 500 mg twice daily Alternatively, as expressed in mg per kg of body weight: 15-40 mg/kg/day divided in 2-3 doses.

Acute ulcerative gingivitis 3 200 mg three times daily 100 mg three times daily 100 mg twice daily 50 mg three times daily Acute dental infections 3-7 200 mg three times daily Leg ulcers and pressure sores 7 400 mg three times daily Children and infants weighing less than 10 kg should receive proportionally smaller dosages.

Elderly:

Metronidazole is well tolerated by the elderly but a pharmacokinetic study suggests cautious use of high dosage regimens in this age group.

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. Method of administration For oral use. Metronidazole Tablets 200mg should be swallowed without chewing, with half a glassful of water, during or after meals.

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 < 1/1000); 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 risk of peripheral neuropathy.

Blood and lymphatic system disorders:

Very rare Agranulocytosis, neutropenia, thrombocytopenia, pancytopenia. Not known Leucopenia. White blood cell counts return to normal once treatment is completed.

Immune system class:

Rare Anaphylaxis Not known Urticaria, angioedema, fever. g. g. ataxia, dysarthria, gait impairment, nystagmus and tremor), which may resolve on discontinuation of drug. Drowsiness, dizziness, convulsions, headaches Not known During intensive and/or prolonged metronidazole therapy, peripheral sensory neuropathy or transient epileptiform seizures have been reported.

These usually disappear after treatment is stopped or dosage reduced.

Aseptic meningitis Eye disorders:

Very rare Diplopia and myopia (which in most cases are transient). Not known Optic neuropathy/neuritis.

Ear and labyrinth disorders:

Not known Hearing impaired/hearing loss (including sensorineural), tinnitus.

Gastrointestinal disorders:

Not known Taste disorders (unpleasant taste in the mouth), oral mucositis, furred tongue, nausea, vomiting, gastrointestinal disturbances such as epigastric pain and diarrhoea.

Hepatobiliary disorders:

Very rare Increase in liver enzymes (AST, ALT, alkaline phosphatase), cholestatic or mixed hepatitis and hepatocellular liver injury, jaundice and pancreatitis which is reversible on drug withdrawal. Cases of liver failure requiring liver transplant have been reported in patients treated with metronidazole in combination with other antibiotic drugs.

Skin and subcutaneous tissue disorders:

Very rare Skin rashes, pustular eruptions, acute generalised exanthematous pustulosis, pruritus, flushing. Not known Erythema multiforme, Stevens-Johnson syndrome or toxic epidermal necrolysis, fixed drug eruption.

Musculoskeletal, connective tissue and bone disorders:

Very rare Myalgia, arthralgia.

Renal and urinary disorders:

Very rare Darkening of urine (due to a metabolite of metronidazole).

Regular clinical and laboratory monitoring (especially leukocyte count) are advised if administration of Metronidazole Tablets 200mg 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. The possibility that an accompanying gonococcal infection might persist in a symptomatic state after Trichomonas vaginalis has been eliminated should be borne in mind.

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 Metronidazole Tablets 200mg needs to 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.

Metronidazole 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. Cases of severe hepatotoxicity/acute hepatic failure, including cases with a fatal outcome with very rapid onset after treatment initiation in patients with Cockayne syndrome have been reported with products containing metronidazole for systemic use.

In this population, metronidazole should therefore be used after careful benefit-risk assessment and only if no alternative treatment is available. Liver function tests must be performed just prior to the start of therapy, throughout and after end of treatment until liver function is within normal ranges, or until the baseline values are reached.

If the liver function tests become markedly elevated during treatment, the drug should be discontinued. Patients with Cockayne syndrome should be advised to immediately report any symptoms of potential liver injury to their physician and stop taking metronidazole.

Cases of severe bullous skin reactions such as Stevens Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) or acute generalised exanthematous pustulosis (AGEP) have been reported with metronidazole. If symptoms or signs of SJS, TEN or AGEP are present, Flagyl treatment must be immediately discontinued.

Patients should be warned that metronidazole may darken urine. Patients with acute porphyria should not take this medicine. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Due to inadequate evidence on the mutagenicity risk in humans, the use of metronidazole for longer treatment than usually required should be carefully considered.

Hypersensitivity to nitroimidazoles, metronidazole or any of the excipients.