- Class: PARP inhibitor (Poly (ADP-ribose) polymerase inhibitor)
- Mechanism of Action:
Inhibits PARP enzymes (mainly PARP-1, PARP-2, and PARP-3), blocking single-strand DNA break repair. This causes accumulation of DNA damage and cancer cell death, especially in tumors with homologous recombination deficiency (HRD) such as BRCA-mutated cancers.
Indications
- Treatment of:
- Adult patients with advanced ovarian, fallopian tube, or primary peritoneal cancer who have been treated with two or more prior lines of chemotherapy and whose cancer is associated with a deleterious BRCA mutation (germline and/or somatic).
- Maintenance therapy:
- For patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy, regardless of BRCA mutation status.
Dosage
- Treatment dose: 600 mg orally twice daily continuously.
- Dose adjustments may be required for toxicity (e.g., hematologic adverse effects, liver impairment).
- Absorption: Oral, peak concentration ~1.9 hours.
- Metabolism: Mainly metabolized by CYP2D6, CYP1A2, and CYP3A4.
- Half-life: ~17 hours.
- Elimination: Mainly via urine and feces.
Key Toxicities and Monitoring
- Common adverse effects:
- Nausea, vomiting
- Fatigue
- Anemia, thrombocytopenia, neutropenia
- Elevated liver enzymes (ALT/AST)
- Dysgeusia (taste changes)
- Serious concerns:
- Myelodysplastic syndrome/acute myeloid leukemia (rare)
- Elevated liver enzymes (usually transient but monitor)
- Monitoring:
- CBC regularly to monitor blood counts.
- Liver function tests at baseline and periodically.
- Renal function.
Drug Interactions
- Avoid strong CYP3A inhibitors or inducers; adjust dose if co-administered.
- Caution with other myelosuppressive agents.