Palbociclib is primarily metabolized by CYP3A and Sulfotransferase (SULT) enzyme SULT2A1. Palbociclib is a
time-dependent inhibitor of CYP3A.
Agents That May Increase Palbociclib Plasma Concentrations: Effect of CYP3A-Inhibitors: Coadministration of a strong CYP3A inhibitor (Itraconazole) increased the plasma exposure of Palbociclib in patients by 87%. Avoid concomitant use of strong CYP3A inhibitors (e.g., Clarithromycin, Indinavir, Itraconazole, Ketoconazole, Lopinavir/Ritonavir, Nefazodone, Nelfinavir, Posaconazole, Ritonavir, Saquinavir, Telaprevir, Telithromycin, And Voriconazole). Avoid grapefruit or grapefruit juice during Palbociclib treatment. If coadministration of Palbociclib with a strong CYP3A inhibitor cannot be avoided, reduce the dose of Palbociclib.
Agents That May Decrease Palbociclib Plasma Concentrations: Effect of CYP3A Inducers: Coadministration of a strong CYP3A Inducer (Rifampin) decreased the plasma exposure of Palbociclib in healthy subjects by 85%. Avoid concomitant use of strong CYP3A inducers (E.G., Phenytoin, Rifampin, Carbamazepine, Enzalutamide, and St John’s Wort).
Drugs That May Have Their Plasma Concentrations Altered By Palbociclib: Coadministration of Midazolam with multiple doses of Palbociclib increased the Midazolam plasma exposure by 61%, in patients, compared to administration of Midazolam alone. The dose of the sensitive CYP3A substrate with a narrow therapeutic index (e.g., Alfentanil, Cyclosporine, Dihydroergotamine, Ergotamine, Everolimus, Fentanyl, Pimozide, Quinidine, Sirolimus, And Tacrolimus) may need to be reduced, as Palbociclib may increase its exposure.
Palbociclib can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively.
Neutropenia: Neutropenia was the most frequently reported adverse reaction. Monitor complete blood counts prior to starting Palbociclib therapy and at the beginning of each cycle, as well as on day 15 of the first 2 cycles, and as clinically indicated. Dose interruption, dose reduction, or delay in starting treatment cycles is recommended for patients who develop grade 3 or 4 neutropenia. Febrile neutropenia has been reported in 1.8% of patients exposed to Palbociclib. One death due to neutropenic sepsis was observed. Physicians should inform patients to promptly report any episodes of fever.
Embryo-Fetal Toxicity: Palbociclib can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with Palbociclib and for at least 3 weeks after the last dose.
There is no known antidote for Palbociclib. The treatment of overdose of Palbociclib should consist of general supportive measures.
Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.
