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Tacrolimus Drug Interaction — RACP Adult Medicine MCQ

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ModerateClinical PharmacologyTacrolimus Drug InteractionRACP Adult Medicine

A 52-year-old man with a transplanted kidney on tacrolimus, mycophenolate, and prednisolone develops persistent diarrhoea and rising tacrolimus levels. His mycophenolate dose has not changed. What is the most likely cause of the rising tacrolimus levels?

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Correct answer: D — Co-administration of a new azole antifungal

While diarrhoea itself can variably affect tacrolimus levels, the scenario of persistently rising levels should prompt investigation for drug interactions. Common culprits include azole antifungals (fluconazole, voriconazole, itraconazole) which are potent CYP3A4 inhibitors and dramatically increase tacrolimus levels. Macrolide antibiotics (erythromycin, clarithromycin), calcium channel blockers (diltiazem), and grapefruit are other CYP3A4 inhibitors. Tacrolimus has a very narrow therapeutic index – supratherapeutic levels cause nephrotoxicity, neurotoxicity, and hyperglycaemia.

Reference: AMH – 2025 – Tacrolimus Drug Interactions; eTG – 2025 – Nephrology