Drug interactions of Palbociclib

Palbociclib is primarily metabolized by CYP3A and sulfotransferase (SULT) enzyme SULT2A1.  In vivo, palbociclib is a time-dependent inhibitor of CYP3A.

1 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 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 Palbociclib treatment. If coadministration of Palbociclib with a strong CYP3A  inhibitor cannot be avoided, reduce the dose of Palbociclib.

2 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).

3 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 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 Palbociclib may increase its exposure.

FDA，2022.12