Talazoparib is a substrate for drug transporters P-gp and BCRP and mainly eliminated by renal clearance as unchanged compound.
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).
| Common name | Source of Evidence | Effect | Clinical 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/T | Data 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]) | T | The 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 agents | CT | Population PK analysis indicates that coadministration of acid-reducing agents had no significant impact on the absorption of talazoparib | Coadministration of acid- reducing agents had no significant impact on the absorption of talazoparib. |
| |||
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).
Interactions with herbal products have not been established.
Interactions with laboratory tests have not been established.
)Talazoparib is a substrate for drug transporters P-gp and BCRP and mainly eliminated by renal clearance as unchanged compound.
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).
| Common name | Source of Evidence | Effect | Clinical 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/T | Data 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]) | T | The 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 agents | CT | Population PK analysis indicates that coadministration of acid-reducing agents had no significant impact on the absorption of talazoparib | Coadministration of acid- reducing agents had no significant impact on the absorption of talazoparib. |
| |||
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).
Interactions with herbal products have not been established.
Interactions with laboratory tests have not been established.
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