Rucaparib
RUBRACA
What it isAn oral PARP inhibitor that traps PARP at sites of DNA damage, causing synthetic lethality in homologous-recombination-deficient (e.g., BRCA-mutated) tumors.
Why this oneIt is used for maintenance of BRCA-mutated recurrent ovarian cancer and for BRCA-mutated metastatic castration-resistant prostate cancer.
What limits itMyelodysplastic syndrome/AML (a PARP-inhibitor class concern) and myelosuppression occur and require monthly CBC monitoring, though these are labeled warnings rather than a boxed warning.
FDA label
Read the full label on DailyMed ↗
| FDA dosing | Population | Start | Target | Max |
|---|---|---|---|---|
| Maintenance treatment, BRCA-mutated recurrent ovarian cancer | Adults | 600 mg BID | 600 mg BID until progression or unacceptable toxicity | 1,200 mg/day |
| BRCA-mutated metastatic castration-resistant prostate cancer (after AR-directed therapy) | Adults | 600 mg BID (with GnRH analog or prior bilateral orchiectomy) | 600 mg BID until progression or unacceptable toxicity | 1,200 mg/day |
Renal No adjustment for mild-moderate (CLcr 30-89 mL/min); not studied if CLcr <30 or on dialysis
Hepatic No adjustment for mild-moderate (bilirubin ≤3x ULN); not studied in severe impairment
Instructions
- With or without food
- Select patients by deleterious BRCA mutation (germline and/or somatic)
- Dose reductions for adverse reactions: 600 → 500 → 400 → 300 mg BID
- Do not start until recovered (≤grade 1) from hematologic toxicity of prior chemotherapy; monitor CBC at baseline and monthly; for hematologic toxicity >4 wks, interrupt/reduce and check counts weekly; discontinue if MDS/AML confirmed
Cautions
- MDS/AML (1.6%, some fatal) — monitor CBC baseline and monthly; discontinue if confirmed
- Embryo-fetal toxicity — female contraception during and 6 mo after; male contraception (and no sperm donation) during and 3 mo after last dose
Adverse reactions
- Nausea
- Fatigue/asthenia
- Anemia
- ALT/AST increased
- Vomiting
- Diarrhea
- Decreased appetite
- Thrombocytopenia
- Dysgeusia
- Neutropenia
- Increased creatinine
- Photosensitivity reaction
- mCRPC additionally: musculoskeletal pain, constipation, edema, rash, peripheral neuropathy
Pregnancy Can cause fetal harm (embryo-fetal death in rats at 0.04x human AUC); pregnancy testing recommended before start; no human data
Lactation Do not breastfeed during treatment and for 2 weeks after last dose
NO BOXED WARNINGS
Principal riskNo FDA boxed warning; MDS/AML is a labeled Warning/Precaution, not a boxed warning.
Classes and tags
Clinical profile
Mechanism of action: Rucaparib ballicule
