Makindo Medical Notes

⚠️ Hepatotoxicity warning: Serious and sometimes fatal liver injury has occurred with oral ketoconazole, even at low doses. Because of this, it should only be considered in the treatment of certain life-threatening systemic mycoses when no safer alternatives are available or tolerated.

📖 About

Synthetic imidazole antifungal. Always check the BNF link here for up-to-date prescribing guidance.

⚙️ Mode of Action

• Inhibits fungal cytochrome P450 enzymes → blocks ergosterol synthesis (disrupts fungal cell membrane).
• Also inhibits human CYP450 steroidogenic enzymes → lowers cortisol and androgens (used off-label in Cushing’s disease – ~50% response rate).

💊 Indications & Dose (specialist use)

• Systemic mycoses (oral use only if no alternative): Blastomycosis, Coccidioidomycosis, Histoplasmosis, Chromomycosis, Paracoccidioidomycosis.
• Topical use: Superficial fungal infections (skin, dandruff, seborrhoeic dermatitis) – generally safe.

🔗 Interactions

• Potent inhibitor of CYP3A4 → major drug–drug interactions (↑ levels of many drugs).

⚠️ Cautions

• Concomitant use with drugs that prolong QT (e.g. dofetilide, quinidine, pimozide, cisapride).
• Monitor LFTs (ALT, AST, bilirubin, ALP), coagulation profile (PT/INR).

🚫 Contraindications

• Should not be used as first-line treatment for any fungal infection.
• History of hepatic disease or previous hepatotoxicity with azoles.

❗ Side Effects

• Hepatotoxicity: ~1 in 15,000 cases can be fatal.
• GI intolerance (nausea, vomiting, abdominal pain).
• QT prolongation → risk of torsades de pointes.

📚 References

• BNF – Ketoconazole
• MHRA Drug Safety Update: Ketoconazole hepatotoxicity risk