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Grapefruit Tacrolimus CYP3A4 — ESENeph MCQ

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EasyTransplantationGrapefruit Tacrolimus CYP3A4ESENeph

A kidney transplant recipient on Tacrolimus develops grapefruit-related toxicity after drinking grapefruit juice daily for 2 weeks. His Tacrolimus trough rises from 6 to 15 ng/mL. What is the mechanism?

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Correct answer: D — Grapefruit juice inhibits intestinal CYP3A4 and P-glycoprotein, dramatically increasing Tacrolimus bioavailability (normally only 20-25%) and leading to supratherapeutic levels and nephrotoxicity

Grapefruit (and Seville orange) juice contains furanocoumarins that irreversibly inhibit intestinal CYP3A4, the enzyme responsible for first-pass metabolism of many drugs including Tacrolimus. This dramatically increases oral bioavailability (Tacrolimus normally has 20-25% bioavailability – can double or triple with grapefruit). The inhibition lasts 24-72 hours after a single exposure (irreversible enzyme inactivation requires new enzyme synthesis). Transplant recipients must be counselled to avoid grapefruit entirely. Similar interactions occur with Ciclosporin, Sirolimus, and many statins.

Reference: BNF 2024 – Tacrolimus Interactions; Bailey et al 2013 – Grapefruit Drug Interactions