METRONIDAZOLE

Seven days’ treatment should be satisfactory for most patients. Prolonged treatment can be used if the physician considers it to be necessary. Recommended doses are given as a guideline based on experience. If therapy is to continue for longer than 10 days, clinical and laboratory monitoring is advised.

Metrolyl* Tablets should be swallowed with water during or after a meal. TREATMENT OF ANAEROBIC INFECTIONS Metronidazole tablets may be given alone or in association with other appropriate bactericidal agents. Adults: 400mg, 3 times daily.

5 mg/kg every 8 hours. The daily dose may be increased to 40 mg/kg, depending on the severity of the infection. Duration of treatment is usually 7 days. 5 mg/kg every 12 hours. In newborns with a gestation age <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.

PROPHYLAXIS AGAINST POSTOPERATIVE INFECTIONS CAUSED BY ANAEROBIC BACTERIA Gynaecological Surgery Adults: 1 gram orally as a single dose followed by 200mg orally, 3 times daily until pre- operative withholding of solids and liquids by mouth becomes necessary.

Oral medication with 200mg, 3 times daily should be resumed after the operation and for up to 7 days.

Children:

Children < 12 years: 20-30 mg/kg as a single dose given 1-2 hours before surgery. Newborns with a gestation age <40 weeks: 10 mg/kg body weight as a single dose before operation. Pre-operative Medication for Elective Colonic Surgery Adults: (i) 200mg orally, 6 hourly co-administered with an aminoglycoside antibiotic for 3 days before surgery.

5g, 6 hourly) for 4 days before surgery.

Children:

Children < 12 years: 20-30 mg/kg as a single dose given 1-2 hours before surgery. Newborns with a gestation age <40 weeks: 10 mg/kg body weight as a single dose before operation. Oral Dosage Regime for Metrolyl* Adults/Childre n over 10 years Children 7-10 years Children 3-7 years Children 1-3 years Urogenital trichomoniasis (treat sexual partners concurrently) 200mg tds x 7d or 400mg bds x 5-7d or 2g once Children < 10 years: 40 mg/kg orally as a single dose or 15 – 30 mg/kg/day divided in 2-3 doses for 7 days; not to exceed 2000 mg/dose.

Bacterial vaginosis 400mg bds x 5- 7d or 2g once Amoebiasis: a) invasive intestinal disease in susceptible subjects 800mg tds x 5d 400mg tds x 5d 200mg qds x 5d 200mg tds x 5d b) intestinal disease in less susceptible subjects and chronic amoebic hepatitis 400mg tds x 5- 10d 200mg tds x 5-10d 100mg qds x 5-10d 100mg tds x 5-10d c) amoebic liver abscess and other forms of extra- intestinal amoebiasis 400mg tds x 5d 200mg tds x 5d 100mg qds x 5d 100mg tds x 5d d) symptomless cyst passers 400mg-800mg tds x 5-10d 200mg- 400mg tds x 5-10d 100mg- 200mg qds x 5-10d 100mg- 200mg tds x 5-10d 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: 2,000mg od x 3d or 400mg tds x 5d or 500mg bds x 7- 10d 1,000mg od x 3d 600mg- 800mg od x 3d 500mg od x 3d Alternatively, as expressed in mg per kg of body weight: 15-40 mg/kg/day divided in 2-3 doses. Acute ulcerative gingivitis: 200mg tds x 3d 100mg tds x 3d 100mg bd x 3d 50mg tds x 3d Acute dental infections: 200mg tds x 3- 7d Leg ulcers and pressure sores: 400mg tds x 7d Proportionately smaller dosages should be given to children and babies weighing less than 10kg.

Eradication of Helicobacter pylori in paediatric patients:

As a part of a combination therapy, 20 mg/kg/day not to exceed 500 mg twice daily for 7-14 days. Official guidelines should be consulted before initiating therapy Method of administration: oral. Metrolyl* Tablets should be swallowed with water during or after a meal.

Serious reactions are rare. An unpleasant taste in the mouth, oral mucositis, furred tongue, nausea, vomiting or other gastro-intestinal disturbance have been reported. There is evidence that metronidazole has been associated with abnormal liver function tests, cholestatic hepatitis and jaundice which may be reversed upon drug withdrawal.

Urticaria, skin rash, pruritus, angioedema and rarely anaphylaxis have occurred. Erythema multiforme has been reported but this resolved on drug withdrawal. Drowsiness, dizziness, headache, confusion, hallucinations, ataxia and darkening of the urine (due to metabolites) have been reported rarely.

Peripheral neuropathy and/or transient epileptiform seizures have occurred during prolonged or intensive treatment but in most cases neuropathy disappears on cessation of therapy. There have been reports of bone marrow depression disorders such as agranulocytosis, leucopenia, neutropenia, thrombocytopenia and pancytopenia which may be reversed on drug withdrawal, although fatalities have been reported.

Other side affects reported include myalgia and arthralgia. 4).

Hepatotoxicity in patients with Cockayne Syndrome:

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 not be used unless the benefit is considered to outweigh the risk and 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. 8). Clinicians considering continuous therapy for relief of chronic conditions are advised to consider the therapeutic benefit against risk of peripheral neuropathy.

Underlying gonococcal infection may persist after elimination of Trichomonas vaginalis. No dose modification is needed in renal failure since the elimination half-life of metronidazole is unchanged in this condition. The clinical significance of retained metabolites is not known; their efficient removal occurs during dialysis so that metronidazole should be re-administered after haemodialysis.

No dosage adjustment is needed for patients undergoing intermittent or continuous ambulatory peritoneal dialysis. Impairment of metronidazole clearance may occur in patients with advanced hepatic insufficiency since the drug is mainly metabolised by hepatic oxidation.

High concentrations of metronidazole may contribute to the symptoms of hepatic encephalopathy - a condition in which significant cumulation may occur. Dose reduction to one-third once daily may be needed. Metronidazole has no activity against aerobic or facultative anaerobic bacteria.

3. Contra-Indications There are no known absolute contraindications for the use of Metrolyl*, however, known sensitivity to metronidazole is an absolute contraindication.