Niraparib

•  Class: PARP inhibitor (Poly (ADP-ribose) polymerase inhibitor)

• Mechanism of Action: Inhibits PARP-1 and PARP-2 enzymes, preventing repair of single-strand DNA breaks. In tumors with homologous recombination deficiency (e.g., BRCA mutations), this leads to accumulation of DNA damage and cancer cell death (synthetic lethality).

Indications

• Maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy.
• Also approved for maintenance therapy regardless of biomarker status (BRCA mutation or homologous recombination deficiency).
• Approved for maintenance treatment in HRR (homologous recombination repair)-deficient metastatic castration-resistant prostate cancer (mCRPC) after response to prior therapy.

Dosage

• Starting dose:
  • Typically 300 mg orally once daily, taken continuously.
  • Dose can be adjusted based on body weight (<77 kg) or platelet count (<150,000/mm³) to reduce risk of hematologic toxicity.

Pharmacokinetics

• Absorption: Oral; peak concentration ~3 hours.
• Metabolism: Primarily by carboxylesterases, minor by CYP enzymes.
• Half-life: ~36 hours.
• Elimination: Mainly fecal and urinary.

Key Toxicities and Monitoring

• Common adverse effects:
  • Hematologic toxicity: thrombocytopenia, anemia, neutropenia
  • Fatigue, Nausea, Hypertension, Insomnia
• Serious risks:
  • Myelodysplastic syndrome/acute myeloid leukemia (rare)
  • Hypertension and cardiovascular events
• Monitoring:
  • CBC regularly to monitor blood counts.
  • Blood pressure monitoring.
  • Liver and renal function tests as indicated.

Drug Interactions: No significant CYP3A4 interactions, but caution with other myelosuppressive agents.