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. The durations of TALZENNA treatment in these three patients prior to developing MDS/AML were 0.3, 2, and 5 years, respectively. 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.

Myelosuppression consisting of anemia, neutropenia, and/or thrombocytopenia have been reported in patients treated with TALZENNA. 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.

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.

TALZENNA can cause fetal harm when administered to pregnant women. Advise women of reproductive potential to use effective contraception during treatment and for 7 months following the last dose of TALZENNA. Verify pregnancy status in females of reproductive potential prior to initiating TALZENNA treatment. Advise male patients with female partners of reproductive potential or who are pregnant to use effective contraception during treatment with TALZENNA and for 4 months after receiving the last dose. Based on animal studies, TALZENNA may impair fertility in males of reproductive potential. Advise women not to breastfeed while taking TALZENNA and for 1 month after receiving the last dose because of the potential for serious adverse reactions in a breastfed child.

Serious adverse reactions of TALZENNA occurred in 32% of patients. Serious adverse reactions reported in >2% of patients included anemia (6%) and pyrexia (2%). Fatal adverse reactions occurred in 1% of patients, including cerebral hemorrhage, liver disorder, veno-occlusive liver disease, and worsening neurological symptoms (1 patient each).

The most common (≥20%) adverse reactions of any grade for TALZENNA vs chemotherapy, including laboratory abnormalities, were hemoglobin decreased (90% vs 77%), neutrophils decreased (68% vs 70%), lymphocytes decreased (76% vs 53%), platelets decreased (55% vs 29%), fatigue (62% vs 50%), glucose increased (54% vs 51%), aspartate aminotransferase increased (37% vs 48%), alkaline phosphatase increased (36% vs 34%), alanine aminotransferase increased (33% vs 37%), calcium decreased (28% vs 16%), nausea (49% vs 47%), headache (33% vs 22%), vomiting (25% vs 23%), alopecia (25% vs 28%), diarrhea (22% vs 26%), and decreased appetite (21% vs 22%).

Clinically relevant adverse reactions in <20% of patients who received TALZENNA included abdominal pain (19%), dizziness (17%), dysgeusia (10%), dyspepsia (10%), stomatitis (8%), and febrile neutropenia (0.3%).

Effect of P-gp Inhibitors: 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. When the P‑gp inhibitor is discontinued, increase the dose of TALZENNA. Coadministration of TALZENNA with these P‑gp inhibitors increased talazoparib concentrations, 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.

Effect of 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. Coadministration of TALZENNA with BCRP inhibitors may increase talazoparib exposure, which may increase the risk of adverse reactions.

Reduce the recommended dosage of TALZENNA in patients with moderate (CLcr 30 – 59 mL/min) and severe (CLcr 15 – 29 mL/min) renal impairment. Monitor patients with severe renal impairment for increased adverse reactions and modify the dosage as recommended for adverse reactions. No dose adjustment is recommended for patients with mild renal impairment (CLcr 60 – 89 mL/min). TALZENNA has not been studied in patients requiring hemodialysis.

TALZENNA is indicated as a single agent for the treatment of adult patients with deleterious or suspected deleterious germline breast cancer susceptibility gene (BRCA)-mutated (gBRCAm) human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer. Select patients for therapy based on an FDA-approved companion diagnostic for TALZENNA.