TALZENNA 9 Drug Interactions

talazoparib

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9.2 Overview

Talazoparib is a substrate for drug transporters P-gp and BCRP and mainly eliminated by renal clearance as unchanged compound.

9.4 Drug-Drug Interactions

Agents that may affect talazoparib plasma concentrations

Effect of P-gp inhibitors  
Data from a drug-drug interaction study in patients with advanced solid tumors indicated that coadministration of multiple daily doses of a P-gp inhibitor, itraconazole 100 mg twice daily, with a single 0.5 mg talazoparib dose increased talazoparib total exposure (AUCinf) and peak concentration (Cmax) by approximately 56% and 40%, respectively, relative to a single 0.5 mg talazoparib dose administered alone. Population pharmacokinetic (PK) analysis has shown that concomitant use of strong P-gp inhibitors with TALZENNA increased talazoparib exposure by 44.7%, relative to TALZENNA given alone. Concomitant use of strong P-gp inhibitors should be avoided. If patients must be coadministered a strong P-gp inhibitor, those that result in ≥2-fold increase in the exposure of an in vivo probe P-gp substrate (including but not limited to amiodarone, carvedilol, clarithromycin, cobicistat, darunavir, dronedarone, erythromycin, indinavir, itraconazole, ketoconazole, lapatinib, lopinavir, propafenone, quinidine, ranolazine, ritonavir, saquinavir, telaprevir, tipranavir, valspodar, and verapamil), the TALZENNA dose should be reduced (see Section 4.2 Recommended Dose and Dosage Adjustment).

Population PK analysis has shown that coadministration with relatively weak P-gp inhibitors (including azithromycin, atorvastatin, diltiazem, felodipine, fluvoxamine, and quercetin) in clinical studies had no significant effect on talazoparib exposure.

Effect of P-gp inducers 
Data from a drug-drug interaction study in patients with advanced solid tumors indicated that coadministration of single 1 mg talazoparib dose with multiple daily doses of a P-gp inducer, rifampin 600 mg, with rifampin co-administered 30 minutes before talazoparib on the day of talazoparib dosing, increased talazoparib Cmax by 37% whereas AUCinf was not affected relative to a single 1 mg talazoparib dose administered alone. This is probably the net effect of both P-gp induction and inhibition by rifampin under the tested conditions in the drug-drug interaction study. No talazoparib dose adjustments are required when coadministered with rifampin. However, the effect of other P-gp inducers on talazoparib exposure has not been studied. Other P-gp inducers (including but not limited to carbamazepine, phenytoin, and St. John’s wort) may decrease talazoparib exposure.

Effect of BCRP inhibitors  
The effect of BCRP inhibitors on PK of talazoparib has not been studied. Concomitant use of strong BCRP inhibitors (including but not limited to curcumin, cyclosporine, and elacridar [GF120918]) should be avoided (see Section 4.2 Recommended Dose and Dosage Adjustment).

Effect of acid-reducing agents 
Population PK analysis indicates that coadministration of acid-reducing agents including proton pump inhibitors (PPI), histamine receptor 2 antagonists (H2RA), or other acid-reducing agents had no significant impact on the absorption of talazoparib.

The drugs listed in this table are based on either drug interaction case reports or studies, or potential interactions due to the expected magnitude and seriousness of the interaction (i.e., those identified as contraindicated).

Table 7 - Established or Potential Drug-Drug Interactions
Common nameSource of EvidenceEffectClinical comment
Agents that may affect talazoparib plasma concentrations
Strong P-gp inhibitor (including but not limited to amiodarone, carvedilol, clarithromycin, cobicistat, darunavir, dronedarone, erythromycin, indinavir, itraconazole, ketoconazole, lapatinib, lopinavir, propafenone, quinidine, ranolazine, ritonavir, saquinavir, telaprevir, tipranavir, valspodar, and verapamil)CT/T

Data from a drug- drug interaction study indicated that coadministration of multiple doses of a strong P-gp inhibitor, itraconazole, with TALZENNA

increased talazoparib total exposure (AUCinf) and peak concentration (Cmax) by approximately 56%

and 40%, respectively, relative to TALZENNA given alone. Population pharmacokinetic (PK) analysis has shown that concomitant use of strong P-gp inhibitors with TALZENNA

increased talazoparib exposure by 44.7%, relative to TALZENNA given alone

If patients must be coadministered a strong P- gp inhibitor reduce the TALZENNA dose to 0.75 mg once daily
Strong P-gp inducers (including but not limited to carbamazepine, rifampin, and St. John’s wort)CT/TData from a drug- drug interaction study indicated that coadministration of multiple doses of a strong P-gp inducer, rifampin, increased talazoparib Cmax by 37% with no effect on talazoparib exposure.Coadministration of rifampin had no significant impact on talazoparib exposure. No talazoparib dose adjustments are required when coadministered with rifampin. However, the effect of other P-gp inducers on the PK of talazoparib has not been studied. Other P- gp inducers (including but not limited to carbamazepine, phenytoin, and St. John’s wort) may decrease talazoparib exposure.
Strong BCRP inhibitors (including but not limited to curcumin, cyclosporine, and elacridar [GF120918])TThe effect of BCRP inhibitors on PK of talazoparib has not been studied.Concomitant use of strong BCRP inhibitors should be avoided
Acid-reducing agents including proton pump inhibitors (PPI), histamine receptor 2 antagonists (H2RA), or other acid-reducing agentsCTPopulation PK analysis indicates that coadministration of acid-reducing agents had no significant impact on the absorption of talazoparibCoadministration of acid- reducing agents had no significant impact on the absorption of talazoparib.
 

Legend: CT = Clinical Trial; T = Theoretical

9.5 Drug-Food Interactions

Food intake decreased the rate but not the extent of talazoparib absorption. Based on these results, TALZENNA can be administered with or without food (see Section 10.3 Pharmacokinetics, Absorption, the effect of food).

9.6 Drug-Herb Interactions

Interactions with herbal products have not been established.

9.7 Drug-Laboratory Test Interactions

Interactions with laboratory tests have not been established.

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9 Drug Interactions

9.2 Overview

Talazoparib is a substrate for drug transporters P-gp and BCRP and mainly eliminated by renal clearance as unchanged compound.

9.4 Drug-Drug Interactions

Agents that may affect talazoparib plasma concentrations

Effect of P-gp inhibitors  
Data from a drug-drug interaction study in patients with advanced solid tumors indicated that coadministration of multiple daily doses of a P-gp inhibitor, itraconazole 100 mg twice daily, with a single 0.5 mg talazoparib dose increased talazoparib total exposure (AUCinf) and peak concentration (Cmax) by approximately 56% and 40%, respectively, relative to a single 0.5 mg talazoparib dose administered alone. Population pharmacokinetic (PK) analysis has shown that concomitant use of strong P-gp inhibitors with TALZENNA increased talazoparib exposure by 44.7%, relative to TALZENNA given alone. Concomitant use of strong P-gp inhibitors should be avoided. If patients must be coadministered a strong P-gp inhibitor, those that result in ≥2-fold increase in the exposure of an in vivo probe P-gp substrate (including but not limited to amiodarone, carvedilol, clarithromycin, cobicistat, darunavir, dronedarone, erythromycin, indinavir, itraconazole, ketoconazole, lapatinib, lopinavir, propafenone, quinidine, ranolazine, ritonavir, saquinavir, telaprevir, tipranavir, valspodar, and verapamil), the TALZENNA dose should be reduced (see Section 4.2 Recommended Dose and Dosage Adjustment).

Population PK analysis has shown that coadministration with relatively weak P-gp inhibitors (including azithromycin, atorvastatin, diltiazem, felodipine, fluvoxamine, and quercetin) in clinical studies had no significant effect on talazoparib exposure.

Effect of P-gp inducers 
Data from a drug-drug interaction study in patients with advanced solid tumors indicated that coadministration of single 1 mg talazoparib dose with multiple daily doses of a P-gp inducer, rifampin 600 mg, with rifampin co-administered 30 minutes before talazoparib on the day of talazoparib dosing, increased talazoparib Cmax by 37% whereas AUCinf was not affected relative to a single 1 mg talazoparib dose administered alone. This is probably the net effect of both P-gp induction and inhibition by rifampin under the tested conditions in the drug-drug interaction study. No talazoparib dose adjustments are required when coadministered with rifampin. However, the effect of other P-gp inducers on talazoparib exposure has not been studied. Other P-gp inducers (including but not limited to carbamazepine, phenytoin, and St. John’s wort) may decrease talazoparib exposure.

Effect of BCRP inhibitors  
The effect of BCRP inhibitors on PK of talazoparib has not been studied. Concomitant use of strong BCRP inhibitors (including but not limited to curcumin, cyclosporine, and elacridar [GF120918]) should be avoided (see Section 4.2 Recommended Dose and Dosage Adjustment).

Effect of acid-reducing agents 
Population PK analysis indicates that coadministration of acid-reducing agents including proton pump inhibitors (PPI), histamine receptor 2 antagonists (H2RA), or other acid-reducing agents had no significant impact on the absorption of talazoparib.

The drugs listed in this table are based on either drug interaction case reports or studies, or potential interactions due to the expected magnitude and seriousness of the interaction (i.e., those identified as contraindicated).

Table 7 - Established or Potential Drug-Drug Interactions
Common nameSource of EvidenceEffectClinical comment
Agents that may affect talazoparib plasma concentrations
Strong P-gp inhibitor (including but not limited to amiodarone, carvedilol, clarithromycin, cobicistat, darunavir, dronedarone, erythromycin, indinavir, itraconazole, ketoconazole, lapatinib, lopinavir, propafenone, quinidine, ranolazine, ritonavir, saquinavir, telaprevir, tipranavir, valspodar, and verapamil)CT/T

Data from a drug- drug interaction study indicated that coadministration of multiple doses of a strong P-gp inhibitor, itraconazole, with TALZENNA

increased talazoparib total exposure (AUCinf) and peak concentration (Cmax) by approximately 56%

and 40%, respectively, relative to TALZENNA given alone. Population pharmacokinetic (PK) analysis has shown that concomitant use of strong P-gp inhibitors with TALZENNA

increased talazoparib exposure by 44.7%, relative to TALZENNA given alone

If patients must be coadministered a strong P- gp inhibitor reduce the TALZENNA dose to 0.75 mg once daily
Strong P-gp inducers (including but not limited to carbamazepine, rifampin, and St. John’s wort)CT/TData from a drug- drug interaction study indicated that coadministration of multiple doses of a strong P-gp inducer, rifampin, increased talazoparib Cmax by 37% with no effect on talazoparib exposure.Coadministration of rifampin had no significant impact on talazoparib exposure. No talazoparib dose adjustments are required when coadministered with rifampin. However, the effect of other P-gp inducers on the PK of talazoparib has not been studied. Other P- gp inducers (including but not limited to carbamazepine, phenytoin, and St. John’s wort) may decrease talazoparib exposure.
Strong BCRP inhibitors (including but not limited to curcumin, cyclosporine, and elacridar [GF120918])TThe effect of BCRP inhibitors on PK of talazoparib has not been studied.Concomitant use of strong BCRP inhibitors should be avoided
Acid-reducing agents including proton pump inhibitors (PPI), histamine receptor 2 antagonists (H2RA), or other acid-reducing agentsCTPopulation PK analysis indicates that coadministration of acid-reducing agents had no significant impact on the absorption of talazoparibCoadministration of acid- reducing agents had no significant impact on the absorption of talazoparib.
 

Legend: CT = Clinical Trial; T = Theoretical

9.5 Drug-Food Interactions

Food intake decreased the rate but not the extent of talazoparib absorption. Based on these results, TALZENNA can be administered with or without food (see Section 10.3 Pharmacokinetics, Absorption, the effect of food).

9.6 Drug-Herb Interactions

Interactions with herbal products have not been established.

9.7 Drug-Laboratory Test Interactions

Interactions with laboratory tests have not been established.

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