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Tacrolimus nephrotoxicity — ESENeph MCQ

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HardRenal TransplantationTacrolimus nephrotoxicityESENeph

Six weeks after kidney transplantation, a patient develops tremor, hypertension and rising creatinine 3 days after clarithromycin is started. Tacrolimus trough concentration is markedly elevated and ultrasound is normal. What is the best explanation?

Educational content. Not a substitute for clinical judgement or local policy.

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Correct answer: BClarithromycin inhibited CYP3A4 and increased tacrolimus exposure

The best answer is “Clarithromycin inhibited CYP3A4 and increased tacrolimus exposure”. The tacrolimus SmPC identifies clarithromycin as a strong CYP3A4 inhibitor that can raise levels within days. The combination should be avoided where possible; if unavoidable, transplant-specialist dose interruption or reduction and frequent trough, renal, neurologic and ECG monitoring are required. “Clarithromycin induced CYP3A4, causing subtherapeutic tacrolimus and immediate rejection” is less appropriate because clarithromycin is a strong inhibitor and raises tacrolimus exposure “Tacrolimus caused post-renal obstruction” is less appropriate because the normal ultrasound and high drug concentration with tremor do not support obstruction “Clarithromycin produced recurrent glomerulonephritis” is less appropriate because the temporal interaction, bland presentation and high trough concentration point to drug toxicity “Tacrolimus increased renal perfusion and generated benign hyperfiltration” is less appropriate because calcineurin-inhibitor excess constricts the renal microcirculation and can impair kidney function

Reference: Advagraf Summary of Product Characteristics: https://www.medicines.org.uk/emc/product/7526/smpc