TALAZOPARIB Drug Interactions: What You Need to Know

INTERACTIONS

• P-gp Inhibitors : Reduce the dose when coadministered with certain P-gp inhibitors. Monitor for increased adverse reactions. ( 2.7 , 7.1 )
• BCRP Inhibitors : Monitor for potential increased adverse reactions. ( 7.1 )

7.1 Effect of Other Drugs on TALZENNA Effect of P-gp Inhibitors Breast Cancer Avoid coadministration of TALZENNA with the following P-gp inhibitors: itraconazole, amiodarone, carvedilol, clarithromycin, itraconazole, and verapamil. If coadministration of TALZENNA with these P-gp inhibitors cannot be avoided, reduce the dose of TALZENNA <span class="opacity-50 text-xs">[see Dosage and Administration (2.7) ]</span> . When the P-gp inhibitor is discontinued, increase the dose of TALZENNA <span class="opacity-50 text-xs">[see Dosage and Administration (2.7) ]</span> . Coadministration of TALZENNA with these P-gp inhibitors increased talazoparib concentrations <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3) ]</span> , which may increase the risk of adverse reactions. Monitor for increased adverse reactions and modify the dosage as recommended for adverse reactions when TALZENNA is coadministered with other P-gp inhibitors <span class="opacity-50 text-xs">[see Dosage and Administration (2.5) ]</span> .

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Gene-mutated mCRPC The effect of coadministration of P-gp inhibitors on talazoparib exposure when TALZENNA is taken with enzalutamide has not been studied. Monitor patients for increased adverse reactions and modify the dosage as recommended for adverse reactions when TALZENNA is coadministered with a P-gp inhibitor [see Dosage and Administration (2.5) ] . Effect of Breast Cancer Resistance Protein (BCRP)

Inhibitors

Monitor patients for increased adverse reactions and modify the dosage as recommended for adverse reactions when TALZENNA is coadministered with a BCRP inhibitor [see Dosage and Administration (2.5) ] . Coadministration of TALZENNA with BCRP inhibitors may increase talazoparib exposure [see Clinical Pharmacology (12.3) ] , which may increase the risk of adverse reactions.

None. None. ( 4 )

AND PRECAUTIONS

• Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML) : MDS/AML occurred in patients exposed to TALZENNA, and some cases were fatal. Monitor patients for hematological toxicity and discontinue if MDS/AML is confirmed. ( 5.1 )
• Myelosuppression : TALZENNA may affect hematopoiesis and can cause anemia, neutropenia, and/or thrombocytopenia. ( 5.2 )
• Embryo-Fetal Toxicity : TALZENNA can cause fetal harm. Advise of the potential risk to the fetus and to use effective contraception. ( 5.3 , 8.1 , 8.3 )

5.1 Myelodysplastic Syndrome/Acute Myeloid Leukemia Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML), including cases with a fatal outcome, has been reported in patients who received TALZENNA. Overall, MDS/AML has been reported in 0.4% (3 out of 788) of solid tumor patients treated with TALZENNA as a single agent in clinical studies. In TALAPRO-2, MDS/AML occurred in 2 out of 511 (0.4%) patients treated with TALZENNA and enzalutamide and in 0 out of 517 (0%) patients treated with placebo and enzalutamide <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> . The durations of TALZENNA treatment in these 5 patients prior to developing MDS/AML were 0.3, 1, 2, 3, and 5 years. Most of these patients had received previous chemotherapy with platinum agents and/or other DNA damaging agents including radiotherapy. Do not start TALZENNA until patients have adequately recovered from hematological toxicity caused by previous chemotherapy. Monitor blood counts monthly during treatment with TALZENNA. For prolonged hematological toxicities, interrupt TALZENNA and monitor blood counts weekly until recovery. If counts do not recover within 4 weeks, refer the patient to a hematologist for further investigations including bone marrow analysis and blood sample for cytogenetics. If MDS/AML is confirmed, discontinue TALZENNA.

5.2 Myelosuppression Myelosuppression consisting of anemia, neutropenia, and/or thrombocytopenia, have been reported in patients treated with TALZENNA <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> . Grade ≥3 anemia, neutropenia, and thrombocytopenia were reported, respectively, in 39%, 21%, and 15% of patients receiving TALZENNA as a single agent. Discontinuation due to anemia, neutropenia, and thrombocytopenia occurred, respectively, in 0.7%, 0.3%, and 0.3% of patients. In TALAPRO-2, Grade ≥3 anemia, neutropenia, and thrombocytopenia were reported, respectively, in 48%, 19%, and 9% of patients receiving TALZENNA and enzalutamide. Forty-two percent of patients (216/511) required a red blood cell transfusion, including 25% (127/511) who required more than one transfusion. Discontinuation due to anemia, neutropenia, and thrombocytopenia occurred, respectively, in 8%, 3%, and 0.4% of patients. Withhold TALZENNA until patients have adequately recovered from hematological toxicity caused by previous therapy. Monitor blood counts monthly during treatment with TALZENNA. If hematological toxicities do not resolve within 28 days, discontinue TALZENNA and refer the patient to a hematologist for further investigations including bone marrow analysis and blood sample for cytogenetics <span class="opacity-50 text-xs">[see Dosage and Administration (2.5) ]</span> .

5.3 Embryo-Fetal Toxicity Based on its mechanism of action and findings from animal data, TALZENNA can cause fetal harm when administered to a pregnant woman. In an animal reproduction study, administration of talazoparib to pregnant rats during the period of organogenesis caused fetal malformations and structural skeletal variations, and embryo-fetal death at exposures that were 0.24 times the area under the concentration-time curve (AUC) in patients receiving the recommended human dose of 1 mg daily. Apprise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for 7 months following the last dose of TALZENNA <span class="opacity-50 text-xs">[see Use in Specific Populations (8.1 , 8.3) , Clinical Pharmacology (12.1) ]</span> . Based on findings from genetic toxicity and animal reproduction studies, advise male patients with female partners of reproductive potential or who are pregnant to use effective contraception during treatment and for 4 months following the last dose of TALZENNA <span class="opacity-50 text-xs">[see Use in Specific Populations (8.1 , 8.3) , Nonclinical Toxicology (13.1) ]</span> .