Increased tacrolimus blood concentration by Beni-Madonna - a new hybrid citrus cultivar categorized as 'Tangor', in a liver transplant patient: likely furanocoumarin-mediated inhibition of CYP3A4 or P-glycoprotein.

ADVERSE EVENT: A drug interaction leading to greater exposure to tacrolimus.

DRUG IMPLICATED: Tacrolimus and Beni-Madonna (a new cultivar citrus categorized as 'Tangor').

THE PATIENT: A 9-month-old girl with biliary atresia (body weight, 7.5 kg) taking tacrolimus after liver transplantation.

EVIDENCE THAT LINKS THE DRUG TO THE EVENT: The time course was consistent with the appearance of the interaction, which was confirmed by an increase in the blood concentration of tacrolimus. Dihydroxybergamottin was detected in peel of Beni-Madonna and in peel and fruit pulp of grapefruit.

MANAGEMENT: Avoiding Beni-Madonna intake.

MECHANISM: Inhibition of activity of CYP3A4, P-glycoprotein, or both, by Beni-Madonna.

IMPLICATION FOR THERAPY: Clinicians should be aware of this potential interaction, and patients taking drugs such as tacrolimus (the kinetics of which are affected by grapefruit juice) should avoid Beni-Madonna intake.

HYPOTHESIS TO BE TESTED: Further study is required to determine if other Citrus species categorized as Tangor contain furanocoumarins.