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Pharmacology · single question

A patient taking simvastatin (a statin) is also prescribed fluconazole. Why is this combination concerning?

  1. Simvastatin reduces antifungal efficacy of fluconazole
  2. Fluconazole causes QT prolongation when combined with statins
  3. Both drugs cause hepatotoxicity through the same pathway
  4. Fluconazole increases simvastatin levels, risking rhabdomyolysis
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Correct answer: D. Fluconazole increases simvastatin levels, risking rhabdomyolysis

Fluconazole is a potent CYP3A4 inhibitor. Simvastatin is metabolized by CYP3A4. When fluconazole inhibits this enzyme, simvastatin plasma levels increase dramatically, raising the risk of rhabdomyolysis (severe muscle breakdown). This interaction is clinically significant and the combination should be avoided or simvastatin dose reduced. This also applies to other CYP3A4-metabolized statins like lovastatin and atorvastatin.
  • A. ❌ Simvastatin does not reduce antifungal efficacy.
  • B. ❌ QT prolongation is not the primary concern of this drug interaction.
  • C. ❌ While both have hepatic metabolism, the primary concern is the drug interaction causing muscle toxicity, not shared hepatotoxic pathways.
  • D. ✅ CORRECT – Fluconazole inhibits CYP3A4, the primary metabolic pathway for simvastatin, leading to dangerously elevated statin levels and risk of rhabdomyolysis.

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