Palbociclib is primarily metabolized by CYP3A and sulfotransferase (SULT) enzyme SULT2A1. In vivo, palbociclib is a time dependent inhibitor of CYP3A.
Agents that may Increase Palbociclib Plasma Concentrations: Effect of CYP3A Inhibitors: Co-administration of a strong CYP3A inhibitor (itraconazole) increased the plasma exposure of palbociclib in healthy subjects 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 IBRANCE treatment. If co-administration of IBRANCE with a strong CYP3A inhibitor cannot be avoided, reduce the dose of IBRANCE [see Dose Modification under Dosage & Administration and Pharmacology: Pharmacokinetics under Actions].
Agents that may Decrease Palbociclib Plasma Concentrations: Effect of CYP3A Inducers: Co-administration 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) [see Pharmacology: Pharmacokinetics under Actions].
Drugs that may have Their Plasma Concentrations Altered by Palbociclib: Co-administration of midazolam with multiple doses of IBRANCE increased the midazolam plasma exposure by 61%, in healthy subjects, 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, IBRANCE may increase its exposure [see Pharmacology: Pharmacokinetics under Actions].