METRONIDAZOLE Film-coated tablet Ref.[6986] Active ingredients: Methronidazole

• Patients should abstain from alcohol for at least 48 hours following discontinuation of therapy with metronidazole. A disulfiram-like reaction with hypotension and flushing has occurred (see section 4.5).
• Caution in patients with epilepsy or those who have had seizures as high doses of Metronidazole can induce seizures.
• 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 Trichomonas vaginalis has been eliminated a gonococcal infection might persist.
• Patients should be warned that metronidazole may darken urine. For information on renal and hepatic insufficiency, please see section 4.2.
• Due to inadequate evidence on the mutagenicity risk in humans (see section 5.3), the use of metronidazole for longer treatment than usually required should be carefully considered.
• Neuropathy (central and peripheral): Regular clinical and laboratory monitoring (especially leukocyte count) are advised if administration of metronidazole 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, vertigo, 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.
• 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. Patients with Cockayne syndrome should be advised to immediately report any symptoms of potential liver injury to their physician and stop taking metronidazole (see section 4.8).
• Skin and subcutaneous tissue disorders: 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, metronidazole treatment must be immediately discontinued.

Interference with laboratory tests

Metronidazole may interfere with certain types of blood test determinations in blood (aminotransferase [ALT], aspartate aminotransferase [AST], lactate dehydrogenase [LDH], triglycerides, glucose), which may lead to false negative or an abnormally low result. These analytical determinations are based on a decrease in ultraviolet absorbance, a fact that occurs when nicotinamide adenine dinucleotide hydrogen (NADH) is oxidised to nicotinamide adenine dinucleotide (NAD). The interference is due to the similarity in the absorption peaks of NADH (340 nm) and metronidazole (322 nm) at pH 7.

Information on sodium content

This medicine contains less than 1 mmol sodium (23 mg) per each tablet, that is to say essentially 'sodium-free'

Lithium

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 concentration of lithium, creatinine, and electrolytes should be monitored in patients under treatment with lithium while they receive metronidazole.

Oral anticoagulant therapy (warfarin type)

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. However, anticoagulant activity should be routinely monitored with these products. There is no interaction with heparin.

Alcohol

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

Disulfiram

Psychotic reactions have been reported in patients who were using metronidazole and disulfiram concurrently.

Phenytoin and phenobarbital

Patients receiving phenobarbital or phenytoin metabolise metronidazole at a much greater rate than normally, reducing the half-life to approximately 3 hours. Primidone accelerates the metabolism of Metronidazole causing reduced plasma concentrations.

5-fluorouracil

Metronidazole reduces the clearance of 5-fluorouraciland can therefore result in increased toxicity of 5-fluorouracil.

Ciclosporin

Patients receiving ciclosporin are at risk of elevated ciclosporin serum levels. Serum ciclosporin and serum creatinine should be closely monitored when coadministration is necessary.

Busulfan

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

Drugs that prolong QT interval

QT prolongation has been reported, particularly when metronidazole was administered with drugs with the potential for prolonging the QT interval.

As with all medicines, metronidazole should not be given during pregnancy or during lactation unless it is considered essential, and in these circumstances the short, high-dosage regimens are not recommended.

Pregnancy

Metronidazole is contraindicated in the first trimester (see section 4.3) and should be used with caution in the second and third trimester when used to treat trichomoniais or bacterial vaginosis (see section 4.4).

For all other indications Metronidazole should only be used if the benefits outweigh the risks or no other alternative is available especially in the first trimester.

Breast-feeding

It is advisable to stop breast feeding until 12–24 hours after Metronidazole therapy has been discontinued (see section 4.3).

Patients should be warned about the potential for drowsiness, dizziness, vertigo, 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 (frequency 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.

Cases of severe irreversible hepatotoxicity/acute liver failure, including cases with fatal outcomes with very rapid onset after initiation of systemic use of metronidazole, have been reported in patients with Cockayne Syndrome (see section 4.4).

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. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Not applicable.