Talazoparib

Indications

Talazoparib is used for: Breast Cancer

Adult Dose

Breast Cancer Indicated for adults with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) HER2-negative locally advanced or metastatic breast cancer 1 mg PO qDay with or without food Continue until disease progression or unacceptable toxicity occurs Hepatic impairment Mild (total bilirubin ?1x ULN and any AST > ULN OR total bilirubin >1-1.5x ULN and any AST): No dosage adjustment Moderate-to-severe (total bilirubin >1.5x ULN AND any AST): Not studied

Child Dose

<18 years: Safety and efficacy not established

Renal Dose

Renal impairment Mild (CrCl 60-89 mL/min): No dosage adjustment Moderate (CrCl 30-59 mL/min): Reduce dose to 0.75 mg qDay Severe (CrCl <30 mL/min) or patients requiring hemodialysis: Not studied

Administration

Administer orally with or without food

Contra Indications

Precautions

Myelosuppression (eg, anemia, leukopenia/neutropenia, and/or thrombocytopenia) reported; monitor CBC count for cytopenia at baseline and monthly thereafter; do not start until patients have adequately recovered from hematological toxicity caused by previous therapy

Pregnancy-Lactation

Pregnancy Based on findings from animal studies and its mechanism of action, embryo-fetal harm may occur when administered to a pregnant woman No data available on use in pregnant women to inform a drug-associated risk Recommend a pregnancy test for females of reproductive potential prior to initiating treatment Animal data In an animal reproduction study, administration of talazoparib to pregnant rats during organogenesis caused fetal malformations and structural skeletal variations and embryo-fetal death at maternal exposures that were 0.24 times the AUC in patients receiving the recommended dose of 1 mg qDay Contraception Females: Advise females of reproductive potential to use effective contraception during treatment and for ?7 months following the last dose Males: Based on genotoxicity and animal reproduction studies, advise males with female partners of reproductive potential and pregnant partners to use effective contraception during treatment and for ?4 months following the last dose Infertility Based on animal studies, impaired fertility in males of reproductive potential may occur Lactation There are no data on the presence of talazoparib in human milk, the drug effects on milk production, or on the breastfed child Because of the potential for serious adverse reactions in a breastfed child, advise lactating women not to breastfeed during treatment and for ?1 month after the final dose

Interactions

In clinical studies, coadministration with P-gp inhibitors (ie, amiodarone, carvedilol, clarithromycin, itraconazole, verapamil) resulted in an ~45% increase in talazoparib exposure and an increase in the rate of talazoparib dose reduction When coadministering with P-gp inhibitors not listed above, monitor for potential increased adverse reactions

Adverse Effects

Side effects of Talazoparib : >10% Decreased hemoglobin (90%) Decreased leukocytes (84%) Decreased lymphocytes (76%) Decreased neutrophils (68%) Fatigue (62%) Decreased platelets (55%) Increased glucose (54%) Anemia (53%) Nausea (49%) Increased AST (37%) Increased alkaline phosphatase (36%) Neutropenia (35%) Increased ALT (33%) Headache (33%) Decreased calcium (28%) Thrombocytopenia (27%) Vomiting (25%) Alopecia (25%) Diarrhea (22%) Decreased appetite (21%) Abdominal pain (19%) Dizziness (17%) Leukopenia (17%) Grade 3 Decreased hemoglobin (39%) Anemia (38%) Neutropenia (18%) Decreased neutrophils (17%) Decreased lymphocytes (17%) Decreased leukocytes (14%) Thrombocytopenia (11%) Decreased platelets (11%) 1-10% Dysgeusia (10%) Dyspepsia (10%) Stomatitis (8%) Lymphopenia (7%) Grade 3 Decreased platelets (4%) Decreased neutrophils (3%) Fatigue (3%) Increased glucose (2%) Increased alkaline phosphate (2%) Vomiting (2%) Headache (2%) Increased AST/ALT (1-2%) Decreased calcium (1%) Grade 4 Thrombocytopenia (4%) Neutropenia (3%) Anemia (1%)

Mechanism of Action

Poly ADP ribose polymerase (PARP) inhibitor; PARP enzymes are involved in normal cellular homeostasis, such as DNA transcription, cell cycle regulation, and DNA repair