indication

For the treatment of anaerobic infections and mixed infections, surgical prophylaxis requiring anaerobic coverage, Clostridium difficile-associated diarrhea and colitis, Helicobacter pylori infection and duodenal ulcer disease, bacterial vaginosis, Giardia lamblia gastro-enteritis, amebiasis caused by Entamoeba histolytica, acne rosacea (topical treatment), and Trichomonas infections.

pharmacology

Metronidazole, a synthetic antibacterial and antiprotozoal agent of the nitroimidazole class, is used against protozoa such as Trichomonas vaginalis, amebiasis, and giardiasis. Metronidazole is extremely effective against anaerobic bacterial infections and is also used to treat Crohn's disease, antibiotic-associated diarrhea, and rosacea.

mechanism of action

Metronidazole is a prodrug. Unionized metronidazole is selective for anaerobic bacteria due to their ability to intracellularly reduce metronidazole to its active form. This reduced metronidazole then covalently binds to DNA, disrupt its helical structure, inhibiting bacterial nucleic acid synthesis and resulting in bacterial cell death.

toxicity

LD50=500 mg/kg/day (orally in rat). Adverse effects include reversible peripheral neuropathy with prolonged therapy, CNS toxicity, disulfiram effect with alcohol, dark red-brown urine, metallic taste, nausea, epigastric distress, dizziness, vertigo and paresthesias associated with high doses, and neutropenia (reversible and mild).

biotransformation

Hepatic metabolism by hydroxylation, oxidation, and glucuronidation.

absorption

Well absorbed (at least 80%) with peak plasma concentrations achieved in 1-3 hours following oral administration of therapeutic doses of immediate release formulation.

half life

6-8 hours

drug interactions

Acenocoumarol: Metronidazole may increase the anticoagulant effect of acenocoumarol.

Amobarbital: The barbiturate, amobarbital, decreases the effect of metronidazole.

Amprenavir: Increased risk of side effects (oral solution)

Anisindione: Metronidazole may increase the anticoagulant effect of anisindione.

Aprobarbital: The barbiturate, aprobarbital, decreases the effect of metronidazole.

Busulfan: Metronidazole increases the effect/toxicity of busulfan

Butabarbital: The barbiturate, butabarbital, decreases the effect of metronidazole.

Butalbital: The barbiturate, butalbital, decreases the effect of metronidazole.

Butethal: The barbiturate, butethal, decreases the effect of metronidazole.

Carbamazepine: Metronidazole increases the effect of carbamazepine

Dicumarol: Metronidazole may increase the anticoagulant effect of dicumarol.

Dihydroquinidine barbiturate: The barbiturate, dihydroquinidine barbiturate, decreases the effect of metronidazole.

Disulfiram: Possible acute psychosis and confusion

Fluorouracil: Risk of 5-FU toxicity when associated with metronidazole

Heptabarbital: The barbiturate, heptabarbital, decreases the effect of metronidazole.

Hexobarbital: The barbiturate, hexobarbital, decreases the effect of metronidazole.

Lithium: Metronidazole increases the effect and toxicity of lithium

Methohexital: The barbiturate, methohexital, decreases the effect of metronidazole.

Methylphenobarbital: The barbiturate, methylphenobarbital, decreases the effect of metronidazole.

Pentobarbital: The barbiturate, pentobarbital, decreases the effect of metronidazole.

Phenobarbital: The barbiturate, phenobarbital, decreases the effect of metronidazole.

Primidone: The barbiturate, primidone, decreases the effect of metronidazole.

Quinidine barbiturate: The barbiturate, quinidine barbiturate, decreases the effect of metronidazole.

Secobarbital: The barbiturate, secobarbital, decreases the effect of metronidazole.

Tacrolimus: Metronidazole increases the levels/toxicity of tacrolimus

Talbutal: The barbiturate, talbutal, decreases the effect of metronidazole.

Tamsulosin: Metronidazole, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Metronidazole is initiated, discontinued, or dose changed.

Tolterodine: Metronidazole may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.

Tramadol: Metronidazole may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.

Trazodone: The CYP3A4 inhibitor, Metronidazole, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Metronidazole is initiated, discontinued or dose changed.

Warfarin: Metronidazole may increase the serum concentration of warfarin by decreasing its metabolism. Consider alternate therapy or a dose reduction in warfarin. Monitor for changes in prothrombin time and therapeutic and adverse effects of warfarin if metronidazole is initiated, discontinued or dose changed.