Systematic Management of a Critical CYP3A4 Interaction Between Cabozantinib and Carbamazepine: A Case Report of a Clinically Relevant Pharmacokinetic Interaction

This was the case of a 62‐year‐old patient treated with cabozantinib and nivolumab for metastatic clear cell renal cell carcinoma, in whom a clinically significant pharmacokinetic interaction with carbamazepine was observed. Carbamazepine, a potent inducer of CYP3A4, caused a major decrease in systemic exposure to cabozantinib, as confirmed by a residual plasma concentration well below the therapeutic target. An adaptation strategy based on identifying the interaction, gradually replacing carbamazepine with a noninducing anticonvulsant, temporarily adjusting the cabozantinib dosage, and close pharmacokinetic monitoring made it possible to restore effective concentrations without toxicity or neurological decompensation. This optimization was accompanied by a significant clinical improvement and radiological tumor control. This case has led to the ongoing need for a medication review before initiating this type of cancer treatment and the implementation of pharmacokinetic monitoring when an interaction was detected.