Chemical formula: C₆H₉N₃O₃ Molecular mass: 171.154 g/mol PubChem compound: 4173
Methronidazole interacts in the following cases:
QT prolongation has been reported particularly when metronidazole was administered with drugs with the potential for prolonging the QT interval.
Concomitant use of metronidazole and CYP3A4 substrates (e.g., amiodarone, tacrolimus, cyclosporine, carbamazepine, and quinidine) may increase respective CYP3A4-substrate plasma levels. Monitoring of plasma concentrations of CYP3A4 substrates may be necessary.
Patients should be advised to discontinue consumption of alcoholic beverages or alcohol-containing products before, during, and up to 72 hours after taking metronidazole because of a disulfram-like effect (abdominal cramps, nausea, headaches, flushing, vomiting and tachycardia).
Caution is needed in patients with severe hepatic impairment. The dose of metronidazole should be reduced as necessary. Metronidazole is mainly metabolised by hepatic oxidation. Substantial impairment of Metronidazole clearance may occur in the presence of advanced hepatic insufficiency. The risk/benefit ratio of using Metronidazole to treat trichomoniasis in such patients should be carefully considered. Plasma levels of Metronidazole should be closely monitored.
Caution is needed in patients with hepatic encephalopathy. Patients with severe hepatic encephalopathy metabolize metronidazole slowly, with resultant accumulation of metronidazole. This may cause exacerbation of CNS adverse effects. The dose of metronidazole should be reduced as necessary.
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.
Broad spectrum antibiotics possibly reduce the contraceptive effect.
Plasma concentrations of busulfan may increase during concomitant treatment with metronidazole, which can result in serious busulfan toxicity such as sinusoidal obstruction syndrome, gastrointestinal mucositis, and hepatic veno-occlusive disease.
Cholestyramine may delay or reduce the absorption of metronidazole.
Patients receiving ciclosporin are at risk of elevated ciclosporin serum levels. Serum ciclosporin and serum creatinine should be closely monitored when coadministration is necessary.
Concomitant administration of drugs that decrease microsomal liver enzyme activity, such as cimetidine, may cause decreased metabolism and reduced plasma clearance of metronidazole which may result in metronidazole toxicity.
Concurrent use of metronidazole and disulfiram may result in psychotic reactions and confusion. Metronidazole should not be given to patients who have taken disulfiram within the last two weeks.
Metronidazole reduces the clearance of 5-fluorouraciland can therefore result in increased toxicity of 5-fluorouracil.
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.
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.
Metronidazole can potentialise the effects of vecuronium.
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 risk of aggravation of the neurological state should be considered in patients with fixed or progressive paraesthesia, epilepsy and active disease of the central nervous system except for brain abscess.
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 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.
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.
Metronidazole is removed during haemodialysis and should be administered after the procedure is finished.
Patients with renal impairment, including patients receiving peritoneal dialysis, should be monitored for signs of toxicity due to the potential accumulation of toxic metronidazole metabolites.
Metronidazole should be used with caution in patients with evidence or history of blood dyscrasia as agranulocytosis, leukopenia and neutropenia have been observed following metronidazole administration.
Metronidazole crosses the placental barrier.
Clinical data on a large number of exposed pregnancies and animal data did not show a teratogenic or foetotoxic effect. However unrestricted administration of nitroimidazolene to the mother may be associated with a carcinogenic or mutagenic risk for the unborn or newborn child.
Metronidazole is contraindicated in the first trimester and should be used with caution in the second and third trimester when used to treat trichomoniais or bacterial vaginosis.
Metronidazole cream is contraindicated during the first third of pregnancy. During the middle and the last third of pregnancy metronidazole cream should only be administered if other treatments have been unsuccessful.
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.
Metronidazole is excreted in breast milk. During lactation either breast-feeding or Metronidazole should be discontinued.
It is advisable to stop breast feeding until 12–24 hours after Metronidazole therapy has been discontinued.
After oral administration, up to 100% of the plasma value can be reached. Following topical application of metronidazole cream the plasma levels are lower than after oral administration of metronidazole. Nevertheless, during lactation breast-feeding should either be interrupted or the treatment with metronidazole cream should be discontinued.
There are no clinical data relating to the effect of metronidazole on fertility.
Animal studies demonstrated adverse effects on the male reproductive system that are wholly or partially reversible after treatment withdrawal.
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.
No studies have been performed following intravenous treatment with metronidazole on the ability to drive and use machines. Some adverse reactions to metronidazole such as seizure, dizziness, optic neuropathy, may impair the ability to drive or operate machines.
Therefore it is recommended that patients should not drive or use machines.
Based upon the pharmacodynamic profile and clinical experience performance related to driving and using machines should not to be affected.
Frequency type and severity of adverse reactions in children are the same as in adults.
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 (<10,000); not known (cannot be estimated from the available data.
Serious adverse reactions occur rarely with standard recommended regime. Frequency, type and severity of adverse reactions in children are the same as in adults.
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, bone marrow depression disorders such as aplastic anaemia
Rare: Anaphylaxis
Not known: Angioedema, urticaria, fever
Not known: Anorexia
Very rare: Psychotic disorders, including hallucinations
Very rare: Encephalopathy (e.g. Confusion, fever, headache, paralysis, light sensitivity, disturbances in sight and movement, stiff neck) and subacute cerebellar syndrome (e.g. Ataxia, dysarthria, gait impairment, nystagmus and tremor) which may resolve on discontinuation of the drug, drowsiness, dizziness, convulsions, headaches
Not known: Depression, paraesthesia, 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
Very rare: Diplopia, myopia
Not known: Unpleasant taste in the mouth, taste disorders, oral mucositis, furred tongue, nausea, vomiting, gastro- intestinal disturbances, diarrhoea, abdominal pain, anorexia
Very rare: Abnormal liver function tests, cholestatic hepatitis, jaundice and pancreatitis which is reversible on drug withdrawal
Very rare: Skin rashes, pustular eruptions, pruritus, flushing
Not known: Erythema multiforme
Very rare: Myalgia, arthralgia
Very rare: Darkening of urine (due to metronidazole metabolite)
There are no data available on adverse reactions from Baxter-sponsored clinical trials conducted with Metronidazole. The following adverse reactions have been reported with Metronidazole, listed by MedDRA System Organ Class (SOC), Preferred Term and frequency. The following frequency groupings are used: very common (≥1/10); common (≥1/100 and <1/10); uncommon (≥1/1,000 and <1/100); rare (≥1/10,000 and <1/1,000); very rare (<1/10,000) and not known (cannot be estimated from the available data).
Frequency, type and severity of adverse reactions in children are the same as in adults.
Uncommon: Leukopenia
Rare: Agranulocytosis, Pancytopenia, Neutropenia, Thrombocytopenia
Not known: Eosinophilia
Rare: Anaphylactic shock, Jarisch-Herxheimer reaction
Not known: Hypersensitivity
Not known: Decreased appetite
Rare: Hallucinations
Not known: Depression, Confusional state, Insomnia
Common: Dysgeusia
Uncommon: Headache
Rare: Encephalopathy, Meningitis aseptic, Seizure, Somnolence, Neuropathy peripheral, Ataxia, Dizziness, Dysarthria
Not known: Hypoaesthesia, Paraesthesia
Rare: Optic neuropathy, Diplopia, Myopia
Not known: Tachycardia, Palpitations
Not known: Dyspnoea
Common: Glossitis, Stomatitis, Dry mouth
Rare: Pancreatitis, Abdominal pain upper, Diarrhoea, Nausea, Vomiting
Not known: Constipation, Tongue discoloration
Rare: Jaundice cholestatic
Rare: Stevens-Johnson syndrome, Toxic epidermal necrolysis, Angioedema, Erythema multiforme
Not known: Pruritus, Swelling face, Urticaria, Hyperhidrosis, Rash
Common: Myalgia
Not known: Muscle spasms, Arthralgia
Rare: Chromaturia
Not known: Dysuria
Uncommon: Asthenia
Rare: Mucosal inflammation, Pyrexia
Not known: Injection site reaction, Malaise, Face oedema, Oedema peripheral, Chest pain, Chills
Not known: Hepatic enzyme increased
The following spontaneous adverse experiences have been reported, and within each system organ class, are ranked by frequency, using the following convention: Very common (≥1/10), Common (≥1/100 <1/10), Uncommon (≥1/1,000 <1/100), Rare (≥1/10,000 <1/1,000), Very rare (<1/10,000), including isolated reports.
Rare: Anaphylaxis
Common: Contact dermatitis, dry skin, erythema, pruritus, rash, skin discomfort (burning and stinging), skin irritation, worsening of rosacea
Rare: Angio-edema
Uncommon: Hypothesia, paraesthesia
Common: Pain
Rare: Metallic taste, nausea
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