Makindo Medical Notes

Tinidazole is a nitroimidazole antimicrobial closely related to metronidazole, with similar activity but a longer plasma half-life (~12–14 h vs 6–8 h). This allows less frequent dosing and shorter courses for certain protozoal and anaerobic infections. Always 🔗 check the BNF entry here for current dose and cautions.

⚙️ Mode of Action

• Tinidazole is a prodrug activated under anaerobic or microaerophilic conditions.
• Its nitro group is reduced by bacterial/parasite nitroreductases, generating reactive intermediates that bind DNA and cause strand breaks and cell death.
• Selective toxicity occurs because human cells lack the anaerobic enzymes needed for activation.

🦠 Indications

• Anaerobic bacterial infections — similar spectrum to metronidazole (e.g. intra-abdominal, pelvic, dental, or postoperative sepsis).
• Protozoal infections:
  • Trichomonas vaginalis (trichomoniasis)
  • Giardia lamblia (giardiasis)
  • Entamoeba histolytica (amoebiasis)
• Helicobacter pylori eradication regimens — sometimes substituted for metronidazole in triple therapy.
• Alternative for metronidazole intolerance (same mechanism but slightly different tolerability profile).

💊 Typical Dosing (Adults)

• Anaerobic infections: 500 mg orally every 12 hours (course duration 5–10 days).
• Trichomoniasis: single 2 g oral dose (treat both partners).
• Giardiasis or amoebiasis: 2 g daily for 3 days.
• H. pylori eradication: 500 mg BD for 5–7 days (as per local antimicrobial guidelines).
• Renal/hepatic impairment: generally no dose adjustment, but monitor for accumulation in severe hepatic disease.

⚖️ Pharmacokinetics

• Bioavailability: ≈100% orally; food delays absorption slightly but reduces GI upset.
• Half-life: 12–14 hours → once or twice daily dosing.
• Metabolism: hepatic via oxidation and conjugation.
• Excretion: urine (major) and faeces; colours urine dark brownish-red (benign effect).

🤝 Interactions

• Warfarin: inhibits hepatic metabolism → ↑ INR → enhanced anticoagulant effect (monitor closely, especially on starting or stopping tinidazole).
• Alcohol: causes a disulfiram-like reaction — facial flushing, nausea, vomiting, tachycardia, hypotension; avoid alcohol during treatment and for 72 h afterwards.
• CYP3A4 inducers (e.g. rifampicin, phenytoin, carbamazepine) may ↓ levels; inhibitors (e.g. cimetidine) may ↑ levels.

⚠️ Cautions

• Liver impairment: metabolised hepatically — use with caution and monitor if prolonged therapy.
• CNS disorders: rare neurotoxicity (encephalopathy, seizures, peripheral neuropathy) with prolonged or high-dose use.
• Pregnancy: avoid in the first trimester unless essential (limited safety data; similar caution as metronidazole).
• Breastfeeding: avoid or withhold feeding for 3 days after therapy due to drug excretion in milk.

⛔ Contraindications

• Known hypersensitivity to nitroimidazoles (metronidazole, tinidazole, secnidazole).
• History of disulfiram-alcohol reaction or concurrent disulfiram therapy.

🥴 Side Effects

• Gastrointestinal: nausea, vomiting, metallic taste, epigastric discomfort.
• Neurological: headache, dizziness, fatigue; very rarely peripheral neuropathy or seizures (usually reversible).
• Allergic: rash, urticaria, pruritus (rare).
• Disulfiram reaction: with concurrent or recent alcohol ingestion.
• Dark urine (benign, due to metabolites).

🧠 Clinical Pearls (UK Practice)

• Tinidazole’s longer half-life allows single-dose therapy for protozoal infections and simpler regimens than metronidazole.
• Always advise complete abstinence from alcohol during therapy and for 72 hours afterwards.
• For polymicrobial intra-abdominal infections, combine with a β-lactam or aminoglycoside for Gram-negative and aerobic cover.
• Can be used in dental abscesses or pelvic infections when metronidazole not tolerated.
• Review for potential drug–warfarin interaction — check INR within 3 days of starting and after stopping therapy.

📚 References

• BNF: Tinidazole
• PHE (UKHSA) Antimicrobial Prescribing Guidelines, 2024.
• NICE NG15: Antimicrobial stewardship.
• Stockley’s Drug Interactions, 12th ed.