Drug Interactions between doxorubicin and sorafenib

MONITOR: Coadministration with sorafenib may increase the plasma concentrations of doxorubicin. The mechanism of interaction has not been described, but may involve inhibition of P-glycoprotein efflux transporter by sorafenib. In a phase I study, concomitant use of doxorubicin (60 mg/m2 every 21 days) with sorafenib (400 mg twice daily, administered with a 3-day break in dosing around administration of doxorubicin) increased the mean peak plasma concentration (Cmax) of doxorubicin by 103% and systemic exposure (AUC) by 47%, but had no apparent impact on clinical toxicity such as myelosuppression or cardiotoxicity. No significant pharmacokinetic changes were observed in patients given lower dosages of sorafenib (100 mg or 200 mg twice daily), and sorafenib pharmacokinetics were not significantly altered by doxorubicin in the study. By contrast, a 21% increase in the AUC of doxorubicin has been cited in the sorafenib labeling.

MANAGEMENT: Caution may be advisable when doxorubicin is used with sorafenib. Patients should be monitored closely for potential toxicities of doxorubicin such as mucositis, myelosuppression and cardiotoxicity, and the dosage adjusted accordingly.