Interactions between abraxane(paclitaxel protein-bound) and Saquinavir mesylate (saquinavir)
saquinavir and paclitaxel protein-bound (Major Drug-Drug)
MONITOR CLOSELY: Coadministration with certain antiretroviral agents such as protease inhibitors and delavirdine may increase the plasma concentrations and pharmacologic effects of taxanes like paclitaxel and docetaxel. The proposed mechanism is inhibition of taxane metabolism via CYP450 3A4. There have been case reports of life-threatening toxicity and death in patients treated with paclitaxel 100 mg/m2 (a dosage previously found to be safe and effective for AIDS-related Kaposi's sarcoma) who were also receiving highly active antiretroviral therapy (HAART) that included ritonavir, ritonavir/lopinavir, indinavir, saquinavir, and/or delavirdine, all of which are known inhibitors of the CYP450 3A4 isoenzyme. Symptoms of toxicity included myalgias, arthralgias, mucositis, febrile neutropenia, leukopenia, thrombocytopenia, infection, alopecia, and ECG abnormalities. A dosage reduction to 60 mg/m2 and concomitant administration with granulocyte colony-stimulating factor (G-CSF) were subsequently required in the patients who recovered.
MANAGEMENT: Caution is advised if taxane therapy is required in patients receiving HAART consisting of protease inhibitors and/or delavirdine. A lower initial dosage of the taxane may be appropriate. Patients should be closely monitored for the development of dose-related taxane toxicity such as myelosuppression, stomatitis, arthralgia, myalgia, visual disturbances and peripheral neuropathy, and the taxane dosage adjusted as necessary.
