UNIGYL Tablet Ref.[115712] Active ingredients: Methronidazole

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 of 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 accumulation 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, Unigyl 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.

Patients should be advised not to take alcohol during therapy and for at least 48 hours afterwards because of the possibility of a disulfiram-like (antabuse effect) reaction.

Concomitant administration of disulfiram has led to acute psychosis and confusional states.

The effects of warfarin type oral anticoagulants may be potentiated by metronidazole. The dose of warfarin type oral anticoagulants may require reduced. 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.

Phenobarbital and Phenytoin causes increased metabolism of metronidazole, reducing the half-life to about three hours.

Metabolism of metronidazole is accelerated by primidone.

Metronidazole inhibits the metabolism of phenytoin (increased plasma concentration). 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 co-administration is necessary.

Plasma levels of busulfan may be increased by metronidazole which may lead to severe busulfan toxicity.

Metronidazole possibly reduces bioavailability of mycophenolate. The metabolism of metronidazole is inhibited by cimetidine.

Antibacterials that do not induce liver enzymes possibly reduce the contraceptive effect of oestrogens.

As there is insufficient evidence on safety of use in pregnancy or lactation, metronidazole should not be given in these circumstances unless it is considered essential by the physician. If it is used, then short-term high dosage therapy is 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 <1/1000); 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.

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.

None known.