Drug Interactions between secobarbital and temsirolimus

GENERALLY AVOID: Coadministration of temsirolimus with inducers of CYP450 3A4 may decrease the plasma concentrations of sirolimus, a major active metabolite of temsirolimus and known substrate of CYP450 3A4. According to the product labeling, administration of temsirolimus in combination with the potent CYP450 3A4 inducer rifampin, resulted in a 65% and 56% decrease in sirolimus peak plasma concentration (Cmax) and systemic exposure (AUC), respectively, compared to administration of temsirolimus alone. No significant effect on the pharmacokinetics of temsirolimus was reported. The extent to which other inducers of CYP450 3A4 interact with temsirolimus is unknown.

MANAGEMENT: In the setting of mantle cell lymphoma, concomitant use of temsirolimus with inducers of CYP450 3A4 should generally be avoided. When used for the treatment of renal cell carcinoma, some authorities advise a dose increase from the recommended 25 mg IV once weekly to 50 mg IV once weekly depending on patient tolerability. Based on pharmacokinetic studies, this dosage is predicted to adjust the sirolimus AUC to the range observed without inducers; however, clinical data are lacking. The dosage should be reduced to the normally recommended dose following discontinuation of the potent CYP450 3A4 inducer. Other authorities also advise that temsirolimus should not be used in combination with CYP450 3A4 inducers for longer than 5 to 7 days in these patients.