Ibrance

Ibrance Drug Interactions

palbociclib

Manufacturer:

Pfizer
The information highlighted (if any) are the most recent updates for this brand.
Full Prescribing Info
Drug Interactions
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: Data from a drug-drug interaction (DDI) study in healthy subjects indicate that coadministration of multiple 200 mg doses of itraconazole with a single 125 mg dose of IBRANCE increased palbociclib total exposure area under the plasma concentration-time curve from time zero to infinity (AUCinf) and the maximum observed plasma concentration (Cmax) by approximately 87% and 34%, respectively, relative to a single 125 mg dose of IBRANCE given alone. The concomitant use of strong CYP3A inhibitors including, but not limited to: amprenavir, atazanavir, boceprevir, clarithromycin, conivaptan, delavirdine, diltiazem, erythromycin, fosamprenavir, indinavir, itraconazole, ketoconazole, lopinavir, mibefradil, miconazole, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole, and grapefruit or grapefruit juice, should be avoided.
Agents that may decrease palbociclib plasma concentrations: Effect of CYP3A inducers: Data from a DDI study in healthy subjects indicate that coadministration of multiple 600 mg doses of rifampin, a strong CYP3A inducer, with a single 125 mg dose of IBRANCE decreased palbociclib AUCinf and Cmax by 85% and 70%, respectively, relative to a single 125 mg dose of IBRANCE given alone. Data from a DDI study in healthy subjects indicate that coadministration of multiple 400 mg daily doses of modafinil, a moderate CYP3A inducer, with a single 125 mg IBRANCE dose decreased palbociclib AUCinf and Cmax by 32% and 11%, respectively, relative to a single 125 mg dose of IBRANCE given alone.
The concomitant use of strong CYP3A inducers including, but not limited to: carbamazepine, enzalutamide, felbamate, nevirapine, phenobarbital, phenytoin, primidone, rifabutin, rifampin, rifapentine, and St. John's wort, should be avoided.
Coadministration of a moderate CYP3A inducer (modafinil) decreased the plasma exposure of palbociclib in healthy subjects by 32%. Moderate CYP3A inducers (e.g., bosentan, efavirenz, etravirine, modafinil, and nafcillin) can be used concurrently with IBRANCE when unavoidable. No dosing adjustments are required.
Effect of acid reducing agents: Data from a DDI study in healthy subjects indicated that coadministration of a single 125 mg dose of IBRANCE with multiple doses of the proton pump inhibitor (PPI) rabeprazole under fed conditions decreased palbociclib Cmax by 41%, but had limited impact on AUCinf (13% decrease) compared with a single 125 mg dose of IBRANCE administered alone.
Given the reduced effect on gastric pH of H2-receptor antagonists and local antacids compared to PPIs, under fed conditions there is no clinically relevant effect of PPIs, H2-receptor antagonists, or local antacids on palbociclib exposure.
Data from another DDI study in healthy subjects indicated that coadministration of a single dose of IBRANCE with multiple doses of the PPI rabeprazole under fasted conditions decreased palbociclib AUCinf and Cmax by 62% and 80%, respectively, when compared with a single dose of IBRANCE administered alone.
Therefore, IBRANCE should be taken with food (see Dosage & Administration).
Effects of IBRANCE on other drugs: Palbociclib is a weak time-dependent inhibitor of CYP3A following daily 125 mg dosing at steady state in humans. In a DDI study in healthy subjects, coadministration of midazolam with multiple doses of palbociclib increased the midazolam AUCinf and Cmax values by 61% and 37%, respectively, as compared with administration of midazolam alone.
Coadministration 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.
In vitro, palbociclib is not an inhibitor of CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, and 2D6, and is not an inducer of CYP1A2, 2B6, 2C8, and 3A4 at clinically relevant concentrations.
Letrozole: Data from a clinical study in patients with breast cancer showed that there was no drug interaction between palbociclib and letrozole when the 2 drugs were coadministered.
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 2 drugs were coadministered.
Goserelin: Data from a clinical study in patients with breast cancer showed that there was no clinically relevant drug interaction between palbociclib and goserelin when the 2 drugs were coadministered.
Tamoxifen: 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 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 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 OCTI and then may increase the exposure of medical product substrates of this transporter (e.g., metformin).
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