Ibrance Drug Interactions

Palbociclib is primarily metabolised by CYP3A and sulphotransferase (SULT) enzyme SULT2A1. In vivo, palbociclib is a weak, time-dependent inhibitor of CYP3A.
Effects of other medicinal products on the pharmacokinetics of palbociclib: Effect of CYP3A inhibitors: Coadministration of multiple 200 mg doses of itraconazole with a single 125 mg palbociclib dose increased palbociclib total exposure (AUC_inf) and the peak concentration (C_max) by approximately 87% and 34%, respectively, relative to a single 125 mg palbociclib dose given alone.
The concomitant use of strong CYP3A inhibitors including, but not limited to: clarithromycin, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, saquinavir, telaprevir, telithromycin, voriconazole, and grapefruit or grapefruit juice, should be avoided (see Dosage & Administration and Precautions).
No dose adjustments are needed for mild and moderate CYP3A inhibitors.
Effect of CYP3A inducers: Coadministration of multiple 600 mg doses of rifampin with a single 125 mg palbociclib dose decreased palbociclib AUC_inf and C_max by 85% and 70%, respectively, relative to a single 125 mg palbociclib dose given alone.
The concomitant use of strong CYP3A inducers including, but not limited to: carbamazepine, enzalutamide, phenytoin, rifampin, and St. John's Wort should be avoided (see Contraindications and Precautions).
Coadministration of multiple 400 mg daily doses of modafinil, a moderate CYP3A inducer, with a single 125 mg IBRANCE dose decreased palbociclib AUC_inf and C_max by 32% and 11%, respectively, relative to a single 125 mg IBRANCE dose given alone. No dose adjustments are required for moderate CYP3A inducers (see Precautions).
Effect of acid reducing agents: Under fed conditions (intake of a moderate-fat meal), coadministration of multiple doses of the proton pump inhibitor (PPI) rabeprazole with a single dose of 125 mg IBRANCE decreased palbociclib C_max by 41%, but had limited impact on AUC_inf (13% decrease) compared with a single dose of 125 mg IBRANCE administered alone.
Under fasting conditions, the coadministration of multiple doses of the PPI rabeprazole with a single dose of 125 mg IBRANCE decreased palbociclib AUC_inf and C_max by 62% and 80%, respectively. Therefore, IBRANCE should be taken with food, preferably a meal (see Dosage & Administration and Pharmacology: Pharmacokinetics under Actions).
Given the reduced effect on gastric pH of H2-receptor antagonists and local antacids compared to PPIs, no clinically relevant effect of H2-receptor antagonists or local antacids on palbociclib exposure is expected when palbociclib is taken with food.
Effects of palbociclib on the pharmacokinetics of other medicinal products: Palbociclib is a weak, time-dependent inhibitor of CYP3A following daily 125 mg dosing at steady state. Coadministration of multiple doses of palbociclib with midazolam increased the midazolam AUC_inf and C_max values by 61% and 37%, respectively, as compared with administration of midazolam alone.
The dose of sensitive CYP3A substrates with a narrow therapeutic index (e.g., alfentanil, cyclosporine, dihydroergotamine, ergotamine, everolimus, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus) may need to be reduced when coadministered with IBRANCE as IBRANCE may increase their exposure.
Drug-drug interaction between palbociclib and letrozole: Data from the drug-drug interaction (DDI) evaluation portion of a clinical study in patients with breast cancer showed that there was no drug interaction between palbociclib and letrozole when the 2 medicinal products were coadministered.
Effect of tamoxifen on palbociclib exposure: Data from a DDI study in healthy male subjects indicated that palbociclib exposures were comparable when a single dose of palbociclib was coadministered with multiple doses of tamoxifen and when palbociclib was given alone.
Drug-drug interaction between palbociclib and fulvestrant: Data from a clinical study in patients with breast cancer showed that there was no clinically relevant drug interaction between palbociclib and fulvestrant when the two medicinal products were coadministered.
Drug-drug interaction between palbociclib and oral contraceptives: DDI studies of palbociclib with oral contraceptives have not been conducted (see Use in Pregnancy & Lactation).
In vitro studies with transporters: Based on in vitro data, palbociclib is predicted to inhibit intestinal P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) mediated transport. Therefore, administration of palbociclib with medicinal products that are substrates of P-gp (e.g., digoxin, dabigatran, colchicine) or BCRP (e.g., pravastatin, rosuvastatin, sulfasalazine) may increase their therapeutic effect and adverse reactions.
Based on in vitro data, palbociclib may inhibit the uptake transporter organic cationic transporter OCT1 and then may increase the exposure of medical product substrates of this transporter (e.g., metformin).