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Metronidazole: Side Effects, Contraindications, and Dosage

Metronidazole is a nitroimidazole antibiotic, which is effective against anaerobic bacteria and protozoa.

Mechanism of Action of Metronidazole

After passive diffusion into the microbes, the nitro group of metronidazole is reduced under anaerobic or hypoxic conditions. This produces highly reactive nitro radical anions, which damage DNA and lead to cell death.

Antibiotic spectrum of metronidazole:

Metronidazole is sensitive against almost all obligate anaerobic bacteria, as well as protozoa such as trichomonads, lamblia, and amoebae.

Urological Indications for Metronidazole:

• For combined antibiotic therapy in infections with possible involvement of anaerobic bacteria, such as intra-abdominal infections or Fournier gangrene.
• Perioperative antibiotic prophylaxis in combination with a cephalosporin for procedures with opening of the bowel
• Bacterial vaginosis
• Infections with trichomonads, amoebas, or lamblia
• Pseudomembranous enterocolitis caused by Clostridium difficile

Pharmacokinetics of Metronidazole:

Good bioavailability after oral administration. Half-life 7–8 hours. Various metabolites are formed in the human body, which are mainly excreted via the kidneys.

Side effects of Metronidazole:

Serious side effects are rare with the dosage listed below and treatment duration for up to one week. With longer treatment, the risk of side effects increases significantly, and there is evidence of an increased mutagenic risk from animal experiments.

Gastrointestinal tract:

Common: taste disorders, nausea, vomiting, diarrhea. Rare: pancreatitis.

Liver:

Common: Increased transaminases. Rare: jaundice, in isolated cases, toxic liver failure.

CNS:

Common: Dizziness, headaches. Rare: ataxia, seizures, delirium, peripheral neuropathies.

Other organ systems:

Dark urine due to metabolites, rash, itching, reversible neutropenia, very rare agranulocytosis.

Contraindications of Metronidazole:

Intolerance to metronidazole, first trimester of pregnancy.

Drug Interactions with Metronidazole:

Metronidazole may elevate blood levels of warfarin, cyclosporine, and lithium. Metronidazole causes severe alcohol intolerance. Psychotic reactions may occur when combined with disulfiram.

Dosage of Metronidazole:

Intravenous dosage: 0.5 g i.v. 1-0-1 or 1-1-1-1. Oral dosage: 0.4 g 1-1-1 or 0.5 g 1-0-1. A dose reduction is necessary in patients with severe liver or kidney insufficiency.

Treatment of Trichomoniasis:

Metronidazole 1500–2000 mg p.o. as a single dose for men. For women, treatment should be administered over seven days: 500 mg 1-0-1 p.o.

References

H. R. Brodt, A. Hörauf, M. Kresken, W. Solbach, and T. Welte, Infektionstherapie: Antibiotika, Virostatika, Antimykotika, Antiparasitäre Wirkstoffe. Thieme, 2023.

E. Zanella and F. Rulli, “A multicenter randomized trial of prophylaxis with intravenous cefepime + metronidazole or ceftriaxone + metronidazole in colorectal surgery. The 230 Study Group,” J Chemother, vol. 12, no. 1, pp. 63–71, 2000.

  Deutsche Version: Metronidazol

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