Source: Υπουργείο Υγείας (CY) Revision Year: 2017 Publisher: Medochemie Ltd, 1-10 Constantinoupoleos Street 3011, Cyprus
Hypersensitivity to metronidazole or any of the excipients listed in section 6.1.
Regular clinical and laboratory monitoring (especially leucocyte 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, 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.
It is possible that after elimination of a Trichomonas vaginalis infection, an underlying gonococcal infection may persist.
In renal impairment the elimination half life of metronidazole remains unchanged, although there is retention of metronidazole metabolites by such patients. The dosage of metronidazole therefore needs no reduction. The clinical significance of this is currently unknown, and caution and careful monitoring is advised in such patients.
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 is needed in patients with renal failure undergoing intermittent peritoneal dialysis (IDP) or continuous ambulatory peritoneal dialysis (CAPD).
Metabolism of metronidazole is mainly due to hepatic oxidation, and metronidazole clearance may be substantially reduced in the presence of advanced hepatic impairment. In patients with hepatic encephalopathy significant accumulation of metronidazole may occur, and the consequential high serum concentration of metronidazole may contribute to the encephalopathic symptoms. A cautious approach in such patients is recommended, and 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.
Patients should be warned that metronidazole may darken urine.
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.
Patients on anticoagulant therapy using warfarin and similar anticoagulants should have prothrombin time regularly monitored and anticoagulant dosage adjusted accordingly (see section 4.5).
Patients should be cautioned not to drink alcohol during metronidazole therapy, or for 48 hours following completion of therapy, due to the risk of a disulfiram-like reaction occurring (see section 4.5).
Klont contains lactose monohydrate (265 mg/tablet). Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Klont contains the colourants tartrazine (E102) and sunset yellow (E110), these are known to cause allergy. This may be more likely in patients predisposed to allergic reactions.
Cyclosporin: serum cyclosporine and serum creatinine should be monitored when co-administration of metronidazole and cyclosporin is necessary. Patients receiving cyclosporine are at risk of elevated cyclosporine serum levels.
Disulfiram: Concurrent use with metronidazole may result in confusion and acute psychoses, such use should be avoided or used with care and close supervision.
Plasma levels of busulfan may be increased by metronidazole which may lead to severe busulfan toxicity.
Fluorouracil: Metronidazole reduces the clearance of 5 fluorouracil and can therefore result in increased toxicity of 5 fluorouracil.
Lithium: simultaneous therapy with lithium and metronidazole has led to reports of lithium retention and possible renal damage. Lithium therapy should be reduced or withdrawn prior to the introduction of metronidazole, and during concomitant medication serum levels of lithium, creatinine, and electrolytes should be monitored for the duration of therapy, and appropriate adjustments made.
Patients receiving phenobarbital or phenytoin metabolise metronidazole at a much greater rate than normally, reducing the half-life to approximately 3 hours.
Warfarin: potentiation of anticoagulant therapy has been reported with warfarin and warfarin type anticoagulants. Anticoagulant dosage may require reduction, and prothrombin time should be monitored in such patients.
Ingestion of alcohol during, or for 48 hours post metronidazole therapy, may result in a disulfiram-like (antabuse effect) reaction, facial flushing, nausea, vomiting, sweating, and patients should be cautioned to avoid alcohol.
Aspartate amino transferase assay: spuriously low values may result from this test, depending upon test methodology employed.
There is inadequate evidence of safety in pregnancy, and there are no adequate and well controlled trials in man. Metronidazole has been in wide spread use for many years without apparent ill consequences.
In common with all other medicines, metronidazole should not be administered in pregnancy, unless the clinician considers it essential. Short, high-dosage regimens are not recommended.
Metronidazole is excreted in breast milk at levels close to those found in serum. It may impart a bitter metallic taste to the milk, which may inhibit feeding. It is recommended that breast feeding be discontinued during metronidazole therapy.
Metronidazole may cause drowsiness, dizziness, confusion, hallucinations, transient visual disorders and convulsions (see “Undesirable Effects”), and patients should be 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 (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.
Very rare: agranulocytosis, neutropenia, thrombocytopenia, pancytopenia.
Not known: leucopenia.
Rare: anaphylaxis.
Not known: angiodema, urticaria, fever.
Not known: anorexia.
Very rare: psychotic disorders, including confusion and hallucinations.
Not known: depressed mood.
Very rare:
Not known:
Very rare: vision disorders such as diplopia and myopia, which, in most cases, is transient.
Not known: optic neuropathy/neuritis.
Not known: taste disorders, oral mucositis, furred tongue, nausea, vomiting, gastro-intestinal disturbances such as epigastric pain and diarrhoea.
Very rare:
Very rare: skin rashes, pustular eruptions, pruritis, flushing.
Not known: erythema multiforme, Stevens-Johnson syndrome or toxic epidermal necrolysis.
Very rare: myalgia, arthralgia.
Very rare: darkening of urine (due to metronidazole metabolite).
Reporting suspected adverse reactions is an important way to gather more information to continuously monitor the benefit/risk balance of the medicinal product. Any suspected adverse reactions should be reported to Pharmaceutical Services, Ministry of Health, CY-1475, www.moh.gov.cy/phs, Fax: +357 22608649.
None known.
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