Purpose.The case of a kidney transplant recipient who experienced a probable drug interaction between sirolimus and ranolazine\r\nis reported. Summary. The narrow therapeutic window of immunosuppressive therapy in transplant recipients requires close\r\nmonitoring for potential drug-drug interactions. The patient, a 57-year-old Caucasian male kidney transplant recipient, was\r\nstable for years on sirolimus as his primary immunosuppressive agent and had a history of chronic angina, for which he was\r\nprescribed ranolazine. Upon addition and dose escalation of ranolazine, whole blood sirolimus levels more than tripled, rising\r\nto immeasurably high concentrations. After holding sirolimus on multiple occasions and reducing dosage more than 50%, blood\r\nlevels returned to therapeutic range, while continuing ranolazine. Conclusion. Since ranolazine is a documented P-GP and CYP3A\r\ninhibitor, and sirolimus a known substrate for both pathways, it is proposed that ranolazine inhibition of P-GP and CYP3A4\r\ncontributed to the significant elevation in sirolimus exposure. No alternative causes for the rise in sirolimus exposure were found,\r\nand assessment with the Drug Interaction Probability Scale finds this interaction to be probable. Clinicians should be aware of the\r\npotential for this interaction to cause elevated sirolimus exposure and subsequent increase in clinical effect or toxicity, in this case\r\noverimmunosuppression.
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