METRONIDAZOLE

For oral administration. Metronidazole 400mg Tablets BP is a round shaped biconvex tablet. Take with or after food. Swallow whole with plenty of water. Do not chew. Duration of treatment will depend upon the clinical and bacteriological response to treatment.

Elderly:

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

Hepatic impairment:

Caution is advised in patients with hepatic encephalopathy. 4).

Anaerobic infections:

Treatment for 7 days should be satisfactory for most patients but, depending upon clinical and bacteriological assessments, the physician may decide to prolong treatment, eg for eradication of infection from sites which cannot be drained or are liable to endogenous recontamination by anaerobic pathogens from the gut, or pharynx or genital tract.

Treatment of established anaerobic infection:

Adults: 800mg initially following by 400mg every 8 hours, usually for 7 days. 5mg/kg every 8 hours. The daily dose may be increased to 40mg/kg, depending on the severity of the infection. Duration of the treatment is usually 7 days. 5mg/kg every 12 hours.

In newborns with a gestation age over the 40 weeks, accumulation of metronidazole can occur during the first week of life, why the concentrations of metronidazole in serum should preferable be monitored after a few days therapy.

Children under 10 years:

A more suitable dosage form should be used for this age group.

Prophylaxis against postoperative infections caused by anaerobic bacteria:

Chiefly in the context of abdominal (especially colorectal) and gynaecological surgery. Adults: 1g start dose 24 hours pre-operatively, followed by 400mg at 8 hourly intervals during the 24 hours preceding operation followed by post-operative iv or rectal administration until the patient is able to take tablets.

Children under 12 years: 20-30mg/kg as a single dose given 1-2 hours before surgery Newborns with a gestation age under 40 weeks: 10mg/kg body weight as a single dose before operation Children under 10 years: A more suitable dosage form should be used for this age group.

Bacterial vaginosis:

Adults: 400mg twice daily for 7 days, or 2g as a single dose for one day only. Adolescents: 400mg twice daily for 5-7 days or 2000mg as a single dose.

Urogenital Trichomoniasis:

Where re-infection is likely, in adults the consort should receive a similar course of treatment concurrently 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 under 10 years: 40mg/kg orally as a single dose or 15-30mg/kg/day divided in 2-3 doses for 7 days; not to exceed 2000mg/dose Children under 10 years: A more suitable dosage form should be used for this age group.

Giardiasis:

Adults, elderly and Children over 10 years: 2000mg once daily for 3 days, or 400mg three times daily for 5 days, or 500mg twice daily for 7-10 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 Alternatively, 35 to 50 mg/kg daily in 3 divided doses for 5 to 10 days, not to exceed 2400 mg/day Children under 7 years: A more suitable dosage form should be used for this age group.

Amoebiasis:

Adults and children over 10 years: 400 to 800 mg 3 times daily for 5-10 days Children 7 to 10 years: 200 to 400 mg 3 times daily for 5-10 days Children 3 to 7 years: 100 to 200 mg 4 times daily for 5-10 days Children 1 to 3 years: 100 to 200 mg 3 times daily for 5-10 days.

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 2400mg/day.

Children under 7 years:

A more suitable dosage form should be used for this age group.

Acute ulcerative gingivitis:

Adults, elderly and children over 10 years: 200mg 3 times daily for 3 days Children 7 to 10 years: 100mg 3 times daily for 3 days Children 3 to 7 years: 100mg 2 times daily for 3 days Children 1 to 3 years: 50mg 3 times daily for 3 days Children under 10 years: A more suitable dosage form should be used for this age.

Acute dental infection:

Adults, elderly and children over 10 years: 200mg 3 times daily for 3-7 days Leg ulcers pressure sores: Adult, elderly and children over 10 years: 400mg 3 times daily for 7 days.

Eradication of Helicobacter pylori in paediatric patients:

As a part of combination therapy, 20mg/kg/day not to exceed 500mg twice daily for 7-14 days. Children and infants weighing less than 10kg should receive proportionally smaller dosages.

Use in the elderly:

Metronidazole is well tolerated by the elderly, but a pharmacokinetic Study suggests cautions use of high dosage regimens in this age group. Official guidelines should be consulted before initiating therapy.

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, and pancytopenia Not known: leucopenia, Immune system disorders: Rare: anaphylaxis, Not known: angioedema, 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.

Incoordination of movement.

Aseptic meningitis Eye disorders:

Very rare: diplopia, myopia, in most cases transient Not known: optic neuropathy/neuritis Gastrointestinal disorders: Not known: unpleasant taste in the mouth, taste disorders, oral mucositis, furred tongue, nausea, vomiting, gastro-intestinal disturbances like epigastric pain, diarrhoea, abdominal pain.

Hepatobiliary disorders:

Very rare: abnormal liver function tests, cholestatic hepatitis, jaundice and pancreatitis which are 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, 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). Frequency, type and severity of adverse reactions in children are the same as in adults.

Reporting of suspected adverse reactions:

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose mal-absorption should not take metronidazole as this product contains lactose. Caution is advised in patients with porphyria.

Metronidazole tablets should not be used in patients with blood dyscrasias or with active non-infectious disease of the central nervous system. High doses of metronidazole may mask the presence of syphilis. Caution in patients with epilepsy or those who have had seizures as high doses of Metronidazole can induce seizures.

) Regular clinical and laboratory monitoring are advised if administration of Metronidazole for more than 10 days is considered 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. Consideration of the therapeutic benefit against the risk of peripheral neuropathy is advised with continuous therapy for chronic conditions.

There is a possibility that after tirchomonas 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 metabolities 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 need be made in patients with renal failure undergoing Intermittent Peritoneal Dialysis (IPD) or Continuous Ambulatory Peritoneal Dialysis (CAPD).

Metronidazole may produce abnormal liver function tests. 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. 3), the use of metronidazole for longer treatment than usually required should be carefully considered.

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.

Known hypersensitivity to nitroimidazoles, metronidazole or any of the excipients. 6). g. 6).