Talazoparib

• Class: PARP inhibitor (Poly (ADP-ribose) polymerase inhibitor)
• Mechanism of Action:
  
  Inhibits PARP-1 and PARP-2 enzymes, blocking repair of single-strand DNA breaks. Talazoparib also traps PARP-DNA complexes more effectively than other PARP inhibitors, leading to increased DNA damage and cancer cell death, particularly in tumors with defective homologous recombination repair (e.g., BRCA-mutated cancers).

Indications

• Treatment of germline BRCA-mutated, HER2-negative locally advanced or metastatic breast cancer.

Dosage

• Standard dose: 1 mg orally once daily.
• Dose adjustments required for renal impairment and for toxicity management.

Pharmacokinetics

• Absorption: Oral, peak plasma concentration ~1–2 hours post-dose.
• Metabolism: Minimal hepatic metabolism (CYP enzymes play minor role).
• Elimination: Mainly renal (~70% unchanged).
• Half-life: ~90 hours.

Key Toxicities and Monitoring

• Common adverse effects:
  • Hematologic: anemia, neutropenia, thrombocytopenia
  • Fatigue
  • Nausea
  • Headache
• Serious risks:
  • Myelodysplastic syndrome/acute myeloid leukemia (rare)
• Monitoring:
  • CBC regularly for hematologic toxicity.
  • Renal function at baseline and during treatment.

Drug Interactions

• Minimal CYP-mediated interactions.
• Avoid concomitant use of strong P-glycoprotein (P-gp) inhibitors (e.g., verapamil, amiodarone) or adjust dose accordingly, as talazoparib is a P-gp substrate.