Rucaparib

RUBRACA

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Pronunciation: roo-KAP-a-rib (roo-BRAH-ka)

Rucaparib ballicule: receptor binding, kinetics and half-life diagram — Mechanism of action: Rucaparib ballicule

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.

Rucaparib molecular structure (skeletal formula) — Molecular structure: Rucaparib

FDA label

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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

Available strengths

tab 200, 250, 300 mg

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

Cost

Rucaparib (RUBRACA)

Strength		#/mo	CostPlus
200 mg	tab	60 BID	not offered
250 mg	tab	60 BID	not offered
300 mg	tab	60 BID	not offered

NADAC is a voluntary CMS survey of what retail community pharmacies pay for the drugs they stock. Rucaparib is dispensed outside retail pharmacies, so it rarely appears on surveyed invoices.

NO BOXED WARNINGS

Principal riskNo FDA boxed warning; MDS/AML is a labeled Warning/Precaution, not a boxed warning.

Classes and tags

Clinical profile

Therapeutic safety burden3 / 4

Overdose danger2 / 4

Weight-gain liability0 / 4

Sedation liability0 / 4

QT / Torsades2 / 4

Direct muscarinic antagonism0 / 4

Embryofetal risk2 / 4

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