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.

MONITOR: Coadministration with celecoxib may increase the plasma concentrations of drugs that are substrates of the CYP450 2D6 isoenzyme. The mechanism is decreased clearance due to inhibition of CYP450 2D6 activity by celecoxib.

MANAGEMENT: Caution is advised if celecoxib must be used concurrently with medications that undergo metabolism by CYP450 2D6, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever celecoxib is added to or withdrawn from therapy.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.