Talazoparib

Talazoparib is an inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes, including PARP1 and PARP2, which play a role in DNA repair. In vitro studies with cancer cell lines that harbored defects in DNA repair genes, including BRCA1 and BRCA2, have shown that Talazoparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complexes resulting in DNA damage, decreased cell proliferation, and apoptosis. Talazoparib anti-tumor activity was observed in patient-derived xenograft breast cancer models bearing mutated BRCA1 or mutated BRCA2 or wild type BRCA1 and BRCA2.

gBRCAm HER2-negative Locally Advanced or Metastatic Breast Cancer: For the treatment of advanced breast cancer with Talazoparib, patients should be selected based on the presence of germline BRCA mutations.

HRR Gene-mutated Metastatic Castration-Resistant Prostate Cancer: For the treatment of HRR gene-mutated mCRPC with Talazoparib, patients should be selected based on the presence of HRR gene mutations (ATM, ATR, BRCA1, BRCA2, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, or RAD51C).

Recommended Dosage for gBRCAm HER2-negative Locally Advanced or Metastatic Breast Cancer: The recommended dosage of Talazoparib is 1 mg taken orally once daily until disease progression or unacceptable toxicity. For adverse reactions, dosing interruption or dose reduction should be considered.

Recommended Dosage for HRR Gene-mutated mCRPC: The recommended dosage of Talazoparib is 0.5 mg taken orally once daily in combination with Enzalutamide until disease progression or unacceptable toxicity. Talazoparib should be taken with or without food. Talazoparib capsules should be swallowed whole. It should not be opened or dissolved. If a patient vomits or misses a dose of Talazoparib, they should be instructed to take the next prescribed dose at the usual time.

Breast Cancer: Coadministration of Talazoparib should be avoided with the following P-gp inhibitors: itraconazole, amiodarone, carvedilol, clarithromycin, itraconazole, and verapamil. If coadministration of Talazoparib with these P-gp inhibitors cannot be avoided, the dose of Talazoparib should be reduced. When the P-gp inhibitor is discontinued, the dose of Talazoparib should be increased. Coadministration of Talazoparib with these P-gp inhibitors increased Talazoparib concentrations, which may increase the risk of adverse reactions. Increased adverse reactions should be monitored and the dosage should be modified as recommended for adverse reactions when Talazoparib is coadministered with other P-gp inhibitors.

HRR Gene-mutated mCRPC: The effect of coadministration of P-gp inhibitors on Talazoparib exposure when Talazoparib is taken in combination with Enzalutamide has not been studied. Increased adverse reactions should be monitored and the dosage should be modified as recommended for adverse reactions when Talazoparib is coadministered with a P-gp inhibitor.

Effect of BCRP Inhibitors: Increased adverse reactions should be monitored and the dosage should be modified as recommended for adverse reactions when Talazoparib is coadministered with a BCRP inhibitor. Coadministration of Talazoparib with BCRP inhibitors may increase Talazoparib exposure, which may increase the risk of adverse reactions.

Most common adverse reactions (>20%) as a single agent, including laboratory abnormalities, are: Hemoglobin decreased, neutrophils decreased, lymphocytes decreased, platelets decreased, fatigue, glucose increased, aspartate aminotransferase increased, alkaline phosphatase increased, alanine aminotransferase increased, calcium decreased, nausea, headache, vomiting, alopecia, diarrhea, and decreased appetite.

Pregnancy: Based on findings from animal studies and its mechanism of action, Talazoparib can cause embryo-fetal harm when administered to a pregnant woman. There are no available data on Talazoparib use in pregnant women to inform a drug-associated risk. Pregnant women and females of reproductive potential should be advised of the potential risk to a fetus.

Lactation: There are no data on the presence of Talazoparib in human milk, the effects of the drug on milk production, or the effects of the drug on the breastfed child.

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 Talazoparib. If MDS/AML is confirmed, discontinue Talazoparib.

Myelosuppression: Myelosuppression consisting of anemia, neutropenia, and/or thrombocytopenia, have been reported in patients treated with Talazoparib. If hematological toxicities do not resolve within 28 days, discontinue Talazoparib and refer the patient to a hematologist for further investigations including bone marrow analysis and blood sample for cytogenetics.

Embryo-Fetal Toxicity: Based on its mechanism of action and findings from animal data, Talazoparib can cause fetal harm when administered to a pregnant woman.

Infertility: Based on animal studies, Talazoparib may impair fertility in males of reproductive potential.

Pediatric Use: The safety and effectiveness of Talazoparib have not been established in pediatric patients.

Geriatric Use: In clinical trials of Talazoparib enrolling 494 patients with advanced solid tumors who received Talazoparib 1 mg daily as a single agent, 85 (17%) patients were >65 years of age, and this included 19 (4%) patients who were >75 years old. There were 5 patients >85 years old. In the TALAPRO-2 trial, of 197 patients who received Talazoparib, 77% were >65 years of age, while 30% were >75 years of age. No overall differences in safety or effectiveness of Talazoparib were observed between these patients and younger patients.

Hepatic Impairment: No dosage modification is recommended for patients with hepatic impairment.

Renal Impairment: The recommended dosage of Talazoparib should be reduced in patients with moderate (CrCl 30-59 mL/min) and severe (CrCl15-29 mL/min) renal impairment. No dose adjustment is recommended for patients with mild renal impairment (CrCl 60-89 mL/min). Talazoparib has not been studied in patients requiring hemodialysis.

Cytotoxic Chemotherapy

Store below 30°C, in a cool and dry place. Keep away from light and keep out of the reach of children.