Ibrelyn Drug Interactions

Palbociclib is primarily metabolised by CYP3A and sulfotransferase (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 (Cmax) 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.
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 Cmax.
The concomitant use of strong CYP3A inducers including, but not limited to: carbamazepine, enzalutamide, phenytoin, rifampin, and St. John's Wort should be avoided.
Coadministration of multiple 400 mg daily doses of modafinil, a moderate CYP3A inducer, with a single 125 mg Palbociclib Capsule dose decreased palbociclib AUC_inf and Cmax. No dose adjustments are required for moderate CYP3A inducers.
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 Palbociclib Capsule decreased palbociclib Cmax, but had limited impact on AUC_inf (decrease) compared with a single dose of 125 mg Palbociclib Capsule administered alone.
Under fasting conditions, the coadministration of multiple doses of the proton pump inhibitor (PPI) rabeprazole with a single dose of 125 mg Palbociclib Capsule decreased palbociclib AUC_inf and Cmax. Therefore, Palbociclib Capsule should be taken with food, preferably a meal.
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 Cmax values.
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 Palbociclib Capsule as Palbociclib Capsule may increase their exposure.
Drug-drug Interaction between Palbociclib and Letrozole: Data shows that there was no drug interaction between palbociclib and letrozole when the 2 medicinal products were coadministered.
Effect of Tamoxifen on Palbociclib Exposure: Data indicates 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 shows 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: There is no data available for use of palbociclib with oral contraceptives.
Data with Transporters: Based on 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 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).