What is the dosing and frequency of metronidazole (Metro)?

Metronidazole Dosing and Frequency

For trichomoniasis, the recommended regimen is metronidazole 2 g orally in a single dose, with an alternative regimen of metronidazole 500 mg twice daily for 7 days. 1

Standard Dosing Regimens by Indication

Trichomoniasis

• First-line treatment: Metronidazole 2 g orally in a single dose 1
• Alternative regimen: Metronidazole 500 mg twice daily for 7 days 1
• FDA has approved Flagyl 375 mg twice daily for 7 days for trichomoniasis based on pharmacokinetic equivalency with metronidazole 250 mg three times daily for 7 days 1

Bacterial Vaginosis (BV)

• Metronidazole 500 mg twice daily for 7 days 1
• Alternative: Metronidazole 2 g orally in a single dose 1

Intraabdominal Infections

• 500 mg every 8 hours (typically for 7-10 days) 2
• Duration may be limited to 4-7 days if adequate source control is achieved 2

Pharmacokinetic Considerations

• Metronidazole has excellent bioavailability (>90%) when administered orally 3
• The elimination half-life is approximately 8 hours in healthy adults 4, 3
• Less than 20% of metronidazole is bound to plasma proteins 4, 3
• The drug is extensively metabolized in the liver with 5 oxidative metabolites 4, 5
• Approximately 60-80% of the dose is excreted in urine, with 6-15% in feces 4
• Only about 20% of the drug is excreted unchanged in urine 4, 3

Special Populations

Pregnancy

• Metronidazole is contraindicated in the first trimester of pregnancy 1
• After the first trimester, 2 g of metronidazole in a single dose can be used 1
• For pregnant women with symptomatic BV, metronidazole 250 mg orally three times daily for 7 days is recommended 1

Renal Dysfunction

• No dosage adjustment is necessary in patients with renal dysfunction 3
• While renal dysfunction reduces elimination of metronidazole metabolites, no toxicity has been documented 3

Hepatic Dysfunction

• Plasma clearance of metronidazole is decreased in patients with decreased liver function 4
• Dosage reduction is recommended in liver disease 3

Treatment Failures and Resistant Infections

• If treatment failure occurs with either standard regimen for trichomoniasis, the patient should be re-treated with metronidazole 500 mg twice daily for 7 days 1
• For repeated treatment failures, a single 2 g dose of metronidazole once daily for 3-5 days is recommended 1
• Resistance to metronidazole is rare but has been documented 5, 3

Common Pitfalls and Caveats

• Metronidazole gel is approved for BV but is not recommended for trichomoniasis as it does not achieve therapeutic levels in the urethra or perivaginal glands 1
• Prolonged or repeated courses of metronidazole should be avoided due to the risk of cumulative and potentially irreversible neurotoxicity 2
• Patients should be instructed to avoid alcohol while taking metronidazole due to potential disulfiram-like reaction 5
• Drug interactions have been reported with alcohol, warfarin, and phenytoin 5
• Clinical studies have demonstrated that twice-daily dosing can be as effective as three-times-daily dosing in certain clinical scenarios, supporting the pharmacokinetic data 6

By following these evidence-based dosing recommendations, clinicians can optimize treatment outcomes while minimizing the risk of adverse effects and antimicrobial resistance.