IBRANCE Drug Interactions

palbociclib

(

Overview

Palbociclib is a substrate and weak inhibitor of CYP3A. It is also a moderate substrate of P-glycoprotein (P-gp) in vitro. Drug interactions were observed when IBRANCE (palbociclib) was coadministered with a strong CYP3A inhibitor and a strong CYP3A inducer. The aqueous solubility of palbociclib is pH-dependent. Drug interaction was observed when IBRANCE capsules were coadministered with proton pump inhibitors (PPIs) under fasted conditions but was limited when IBRANCE capsules were coadministered with PPIs under fed conditions. Food intake with administration of IBRANCE capsules reduced the variability of palbociclib exposure. Coadministration of IBRANCE tablets with PPIs under fasted conditions had no effect on palbociclib absorption. 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.

Drug-Drug Interactions

Agents that may increase palbociclib plasma concentrations

CYP3A Inhibitors: Data from a study in 12 healthy subjects indicate that coadministration of multiple 200 mg daily doses of itraconazole with a single 125 mg IBRANCE dose increased palbociclib total exposure (area under the curve, AUCinf) and the peak exposure (Cmax) by approximately 87% and 34%, respectively, relative to a single 125-mg IBRANCE dose given alone. The concomitant use of strong CYP3A inhibitors including, but are not limited to: clarithromycin, indinavir, itraconazole, ketoconazole, lopinavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole, and grapefruit or grapefruit juice, should be avoided.

Agents that may decrease palbociclib plasma concentrations

CYP3A Inducers: Data from a study in 14 healthy subjects indicated that coadministration of multiple 600 mg doses of rifampin, a strong CYP3A inducer, with a single 125 mg IBRANCE dose decreased palbociclib AUCinf and Cmax by 85% and 70%, respectively, relative to a single 125 mg IBRANCE 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.

Data from a drug interaction study in healthy subjects (N=14) indicated 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 IBRANCE dose given alone.  If concomitant use of IBRANCE with moderate CYP3A inducers (e.g., bosentan, efavirenz, etravirine, modafinil, and nafcillin) cannot be avoided, no dosing adjustments are required for IBRANCE.

Gastric pH Elevating Medications:

Capsules: Data from a study in healthy subjects indicated that coadministration of a single 125 mg IBRANCE capsule with multiple doses of the PPI rabeprazole under fed conditions decreased palbociclib Cmax by 41%, but had limited impact on AUCinf (13% decrease) compared with a single 125 mg IBRANCE capsule administered alone. Given the reduced effect on gastric pH of H2 receptor antagonists and local antacids compared to PPIs, the effect of these classes of acid reducing agents on palbociclib exposure under fed conditions is expected to be minimal.

Data from another study in healthy subjects indicated that coadministration of a single 125 mg IBRANCE capsule 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 125 mg IBRANCE capsule administered alone. 

IBRANCE capsules should be taken with food.

Tablets: Data from a study in healthy subjects indicated that coadministration of a single 125 mg IBRANCE tablet with multiple doses of the PPI rabeprazole under fasted conditions had no effect on the rate and extent of absorption of palbociclib when compared to a single 125 mg IBRANCE tablet administered alone. The effect of coadministration of a single 125 mg IBRANCE tablet with multiple doses of the PPI rabeprazole under fed conditions have not been evaluated in clinical studies.

Given the reduced effect on gastric pH of H2 receptor antagonists and local antacids compared to PPIs, the effect of these classes of acid reducing agents on palbociclib exposure is expected to be minimal.

Drugs That May Have Their Plasma Concentrations Altered by Palbociclib

CYP3A Substrates: Palbociclib is a weak time-dependent inhibitor of CYP3A following daily 125 mg dosing at steady state in humans. In a study in 26 healthy subjects, coadministration of midazolam with multiple doses of IBRANCE increased the midazolam AUCinf and the Cmax values by 61% and 37%, respectively, as 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 their exposure.

Luteinizing Hormone Releasing Hormone (LHRH) Agonists 
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. Drug-drug interaction studies between palbociclib and other LHRH agonists have not been performed.

In vitro studies with transporters 
In vitro evaluations indicated that palbociclib has a low potential to inhibit the activities of drug transporters P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), organic anion transporter (OAT)1, OAT3, organic cation transporter (OCT)1, OCT2, organic anion transporting polypeptide (OATP)1B1, and OATP1B3 at clinically relevant concentrations.

In vitro studies demonstrate that palbociclib is not a substrate of OATP1B1 or OATP1B3.

Drug-Food Interactions 
Grapefruit, grapefruit juice, and products containing grapefruit extract may increase palbociclib plasma concentrations and should be avoided.

Capsules: The effect of food on palbociclib exposure following administration of IBRANCE capsules was evaluated in healthy subjects. Compared to IBRANCE capsules given under overnight fasted conditions, the AUCinf and Cmax of palbociclib increased by 21% and 38% when given with high-fat food, by 12% and 27% when given with low-fat food, and by 13% and 24% when moderate-fat food was given 1 hour before and 2 hours after IBRANCE capsule dosing. In addition, food intake significantly reduced the inter-subject and intra-subject variability of palbociclib exposure. Based on these results, IBRANCE capsules should be taken with food.

Tablets: The effect of food on palbociclib exposure following administration of IBRANCE tablets was evaluated in healthy subjects. Compared to IBRANCE tablets given under overnight fasted conditions, the AUCinf and Cmax of palbociclib increased by 22% and 26%, respectively, when IBRANCE tablets were given with a high-fat, high-calorie meal, and by 9% and 10%, respectively, when IBRANCE tablets were given with a moderate-fat, standard-calorie meal. Food intake had no significant impact on the variability of palbociclib exposure following administration with IBRANCE tablets. Based on these results, IBRANCE tablets may be taken with or without food.

Drug-Herb Interactions 
Interactions with herbal products have not been established. St. John’s wort (Hypericum perforatum) is an inducer of CYP3A4/5 that may decrease palbociclib plasma concentrations and should be avoided.

Drug-Laboratory Interactions 
Interactions between IBRANCE and laboratory tests have not been studied.

Drug-Lifestyle Interactions 
Interactions between IBRANCE and lifestyle have not been studied.

)

Find IBRANCE medical information:

Find IBRANCE medical information:

Our scientific content is evidence-based, scientifically balanced and non-promotional. It undergoes rigorous internal medical review and is updated regularly to reflect new information.

IBRANCE Quick Finder

Product Monograph
Download Product Monograph

Health Professional Information

Drug Interactions

Overview

Palbociclib is a substrate and weak inhibitor of CYP3A. It is also a moderate substrate of P-glycoprotein (P-gp) in vitro. Drug interactions were observed when IBRANCE (palbociclib) was coadministered with a strong CYP3A inhibitor and a strong CYP3A inducer. The aqueous solubility of palbociclib is pH-dependent. Drug interaction was observed when IBRANCE capsules were coadministered with proton pump inhibitors (PPIs) under fasted conditions but was limited when IBRANCE capsules were coadministered with PPIs under fed conditions. Food intake with administration of IBRANCE capsules reduced the variability of palbociclib exposure. Coadministration of IBRANCE tablets with PPIs under fasted conditions had no effect on palbociclib absorption. 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.

Drug-Drug Interactions

Agents that may increase palbociclib plasma concentrations

CYP3A Inhibitors: Data from a study in 12 healthy subjects indicate that coadministration of multiple 200 mg daily doses of itraconazole with a single 125 mg IBRANCE dose increased palbociclib total exposure (area under the curve, AUCinf) and the peak exposure (Cmax) by approximately 87% and 34%, respectively, relative to a single 125-mg IBRANCE dose given alone. The concomitant use of strong CYP3A inhibitors including, but are not limited to: clarithromycin, indinavir, itraconazole, ketoconazole, lopinavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole, and grapefruit or grapefruit juice, should be avoided.

Agents that may decrease palbociclib plasma concentrations

CYP3A Inducers: Data from a study in 14 healthy subjects indicated that coadministration of multiple 600 mg doses of rifampin, a strong CYP3A inducer, with a single 125 mg IBRANCE dose decreased palbociclib AUCinf and Cmax by 85% and 70%, respectively, relative to a single 125 mg IBRANCE 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.

Data from a drug interaction study in healthy subjects (N=14) indicated 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 IBRANCE dose given alone.  If concomitant use of IBRANCE with moderate CYP3A inducers (e.g., bosentan, efavirenz, etravirine, modafinil, and nafcillin) cannot be avoided, no dosing adjustments are required for IBRANCE.

Gastric pH Elevating Medications:

Capsules: Data from a study in healthy subjects indicated that coadministration of a single 125 mg IBRANCE capsule with multiple doses of the PPI rabeprazole under fed conditions decreased palbociclib Cmax by 41%, but had limited impact on AUCinf (13% decrease) compared with a single 125 mg IBRANCE capsule administered alone. Given the reduced effect on gastric pH of H2 receptor antagonists and local antacids compared to PPIs, the effect of these classes of acid reducing agents on palbociclib exposure under fed conditions is expected to be minimal.

Data from another study in healthy subjects indicated that coadministration of a single 125 mg IBRANCE capsule 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 125 mg IBRANCE capsule administered alone. 

IBRANCE capsules should be taken with food.

Tablets: Data from a study in healthy subjects indicated that coadministration of a single 125 mg IBRANCE tablet with multiple doses of the PPI rabeprazole under fasted conditions had no effect on the rate and extent of absorption of palbociclib when compared to a single 125 mg IBRANCE tablet administered alone. The effect of coadministration of a single 125 mg IBRANCE tablet with multiple doses of the PPI rabeprazole under fed conditions have not been evaluated in clinical studies.

Given the reduced effect on gastric pH of H2 receptor antagonists and local antacids compared to PPIs, the effect of these classes of acid reducing agents on palbociclib exposure is expected to be minimal.

Drugs That May Have Their Plasma Concentrations Altered by Palbociclib

CYP3A Substrates: Palbociclib is a weak time-dependent inhibitor of CYP3A following daily 125 mg dosing at steady state in humans. In a study in 26 healthy subjects, coadministration of midazolam with multiple doses of IBRANCE increased the midazolam AUCinf and the Cmax values by 61% and 37%, respectively, as 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 their exposure.

Luteinizing Hormone Releasing Hormone (LHRH) Agonists 
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. Drug-drug interaction studies between palbociclib and other LHRH agonists have not been performed.

In vitro studies with transporters 
In vitro evaluations indicated that palbociclib has a low potential to inhibit the activities of drug transporters P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), organic anion transporter (OAT)1, OAT3, organic cation transporter (OCT)1, OCT2, organic anion transporting polypeptide (OATP)1B1, and OATP1B3 at clinically relevant concentrations.

In vitro studies demonstrate that palbociclib is not a substrate of OATP1B1 or OATP1B3.

Drug-Food Interactions 
Grapefruit, grapefruit juice, and products containing grapefruit extract may increase palbociclib plasma concentrations and should be avoided.

Capsules: The effect of food on palbociclib exposure following administration of IBRANCE capsules was evaluated in healthy subjects. Compared to IBRANCE capsules given under overnight fasted conditions, the AUCinf and Cmax of palbociclib increased by 21% and 38% when given with high-fat food, by 12% and 27% when given with low-fat food, and by 13% and 24% when moderate-fat food was given 1 hour before and 2 hours after IBRANCE capsule dosing. In addition, food intake significantly reduced the inter-subject and intra-subject variability of palbociclib exposure. Based on these results, IBRANCE capsules should be taken with food.

Tablets: The effect of food on palbociclib exposure following administration of IBRANCE tablets was evaluated in healthy subjects. Compared to IBRANCE tablets given under overnight fasted conditions, the AUCinf and Cmax of palbociclib increased by 22% and 26%, respectively, when IBRANCE tablets were given with a high-fat, high-calorie meal, and by 9% and 10%, respectively, when IBRANCE tablets were given with a moderate-fat, standard-calorie meal. Food intake had no significant impact on the variability of palbociclib exposure following administration with IBRANCE tablets. Based on these results, IBRANCE tablets may be taken with or without food.

Drug-Herb Interactions 
Interactions with herbal products have not been established. St. John’s wort (Hypericum perforatum) is an inducer of CYP3A4/5 that may decrease palbociclib plasma concentrations and should be avoided.

Drug-Laboratory Interactions 
Interactions between IBRANCE and laboratory tests have not been studied.

Drug-Lifestyle Interactions 
Interactions between IBRANCE and lifestyle have not been studied.

Resources

Didn’t find what you were looking for? 

Contact us

Call 1-800-463-6001*

*Contact Medical Information. 9AM-5PM ET Monday to Friday; excluding holidays.

Medical Inquiry

Submit a medical question for Pfizer prescription products.

Report Adverse Event

Pfizer Safety

Contact Pfizer Safety to report an adverse event, side effect or concern about the quality of a Pfizer product: 1 866 723-7111.

To report an adverse event related to COMIRNATY, and you are not part of a clinical trial* for this product, click the link below to submit your information:

Pfizer Safety Reporting Site

*If you are involved in a clinical trial for this product, adverse events should be reported to your coordinating study site.

Canada Vigilance Program 

You may also contact the Canada Vigilance Program directly to report adverse events or product quality concerns at 1-866-234-2345 or www.healthcanada.gc.ca/medeffect