Drug Interaction Report

MONITOR: Coadministration of carboplatin with other nephrotoxic agents may increase the risk of renal impairment due to additive effects on the kidney. Moreover, renal impairment secondary to the use of these agents may reduce the clearance of carboplatin, which is primarily eliminated by renal excretion. This may increase the risk of other adverse effects including severe myelosuppression which is concentration-dependent. Approximately 25% of patients receiving carboplatin exhibit decreases in creatinine clearance, whereas rises in serum creatinine and blood urea nitrogen occur less frequently. Some data suggests hypomagnesemia is the primary indicator of carboplatin-induced nephrotoxicity. Patients receiving multiple courses or single doses exceeding 800 mg/m2 of carboplatin, or those with a history of cisplatin-induced nephrotoxicity, may be at increased risk of renal toxicity.

MANAGEMENT: Renal function and serum magnesium levels should be monitored if carboplatin is used concomitantly with other nephrotoxic agents. The potential for increased toxicity of carboplatin such as peripheral sensory neuropathies and myelosuppression should be considered.

ADJUST DOSING INTERVAL: Food significantly enhances the oral bioavailability of alectinib and its major active metabolite, M4. According to the manufacturer, a high-fat, high-calorie meal increased the combined systemic exposure (AUC) of alectinib and M4 by 3.1-fold following oral administration of a single 600 mg dose of alectinib.

MANAGEMENT: To ensure maximal oral absorption, alectinib should be administered with food.