Drug Interactions between aprocitentan and paclitaxel

Consumer information for this interaction is not currently available.

MONITOR: Coadministration with inhibitors of CYP450 2C8 and/or 3A4 may increase the plasma concentrations of paclitaxel, which has been found in vitro to be a substrate of these isoenzymes. Formal clinical drug interaction studies have not been conducted. However, in a case report involving a 77-year-old woman with HER2-positive invasive ductal breast cancer on long-term amiodarone therapy, 4 cycles of paclitaxel (80 mg/m2 weekly) and trastuzumab led to development of increasing abdominal discomfort and skin lesions and a diagnosis of paclitaxel-induced skin toxicity. Switching to reduced dose docetaxel (100 mg or 75 mg/m2 weekly) led to the development of severe skin and mucosal toxicity, requiring hospitalization 8 days after the first docetaxel dose was administered. Analysis of two blood samples taken 9 and 10 days after docetaxel administration showed an approximately fivefold increase in its AUC as well as the presence of paclitaxel in unquantifiable levels, 20 and 21 days after it was last administered. The authors of this case study propose that, in addition to CYP450 3A4 inhibition, CYP450 2C8 and P-glycoprotein inhibition due to amiodarone may also contribute to the interaction.

MANAGEMENT: Clinicians should consider the potential for interaction with drugs that inhibit CYP450 2C8 and/or 3A4 and monitor for evidence of dose-related toxicities of paclitaxel during coadministration, including diarrhea, mucositis, myelosuppression, and peripheral neuropathy.