Severe rise in tacrolimus levels following blood orange and grapefruit juice intake in a kidney transplant recipient: a case report.

backgroundTacrolimus is a cornerstone immunosuppressant in kidney transplantation with a narrow therapeutic index and high interindividual pharmacokinetic variability, largely determined by CYP3A4, CYP3A5, and P-glycoprotein activity. Grapefruit juice is a known intestinal CYP3A4 inhibitor capable of increasing tacrolimus exposure, whereas blood orange juice has not been documented to exert such effects. CASE PRESENTATION: A 33-year-old male kidney transplant recipient of Somali origin had persistently low tacrolimus trough levels, averaging about 4.5 µg/L, despite increased dosing. On postoperative day 5 (POD 5), the patient consumed approximately one liter of blood orange juice followed later the same evening by a clinically supervised 250 mL dose of grapefruit juice intended to enhance tacrolimus exposure. The following morning, his tacrolimus concentration had risen sharply sixfold to 30 µg/L, far above the increase typically associated with grapefruit juice alone. Kidney biopsy at that time showed eosinophilic infiltration, consistent with a drug-related inflammatory reaction. Tacrolimus therapy was temporarily stopped, then gradually reintroduced. His condition stabilized, and he was discharged on POD 12.

conclusionsThe pronounced increase in tacrolimus exposure following sequential ingestion of blood orange and grapefruit juice suggests a potential synergistic interaction affecting tacrolimus disposition via CYP3A4, CYP3A5 and/or P-glycoprotein pathways. While causality remains unconfirmed, this case emphasizes the value of thorough dietary history in transplant care and supports further research on blood orange juice as a possible modulator of tacrolimus pharmacokinetics.