RUBRACA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for RUBRACA (RUBRACA).
Rucaparib is a poly(ADP-ribose) polymerase (PARP) inhibitor, including PARP1, PARP2, and PARP3. It inhibits PARP enzymatic activity and traps PARP-DNA complexes, leading to DNA damage, apoptosis, and cell death in tumor cells with homologous recombination repair deficiencies (e.g., BRCA mutations).
| Metabolism | Primarily metabolized by CYP2D6 and CYP3A4; minor contributions from CYP1A2, CYP2C9, CYP2C19, and CYP2E1. |
| Excretion | Approximately 44% of the administered dose is excreted in feces (with 38% as unchanged drug) and 28% in urine (with 7% as unchanged drug). The remainder is recovered as metabolites in feces and urine, with biliary excretion being a minor route. |
| Half-life | The terminal elimination half-life (t1/2) is approximately 17 hours, supporting twice-daily dosing (600 mg twice daily) to maintain steady-state concentrations within the therapeutic window. |
| Protein binding | Approximately 37–40% bound to human plasma proteins, primarily albumin and alpha-1-acid glycoprotein, with minimal concentration dependence over the therapeutic range. |
| Volume of Distribution | The apparent volume of distribution (Vd/F) is approximately 155 L (2.2 L/kg for a 70 kg adult), indicating extensive distribution into tissues, including penetration into tumor tissue. |
| Bioavailability | Absolute oral bioavailability is approximately 50% (range 30–80%). Administration with a high-fat meal increases AUC by 56% and Cmax by 36%; therefore, rucaparib should be taken with or without food consistently. |
| Onset of Action | Following oral administration, peak plasma concentrations are achieved at a median Tmax of 2–4 hours, with inhibition of poly(ADP-ribose) polymerase (PARP) enzymatic activity observed within hours. Clinical antitumor effects typically require 4–8 weeks of continuous therapy for initial tumor shrinkage. |
| Duration of Action | The pharmacodynamic effect (inhibition of PARP activity in tumor cells) persists for approximately 24–48 hours after a single dose, but continuous daily dosing is required for sustained antitumor efficacy. Steady state is reached after 3–5 days of twice-daily dosing. |
600 mg orally twice daily, with or without food, total daily dose 1200 mg.
| Dosage form | TABLET |
| Renal impairment | CrCl 30-89 mL/min: no adjustment; CrCl 15-29 mL/min: reduce to 200 mg twice daily; CrCl <15 mL/min or on dialysis: not recommended. |
| Liver impairment | Child-Pugh A: 600 mg twice daily; Child-Pugh B: reduce to 200 mg twice daily; Child-Pugh C: not recommended. |
| Pediatric use | Safety and efficacy not established; no specific dosing guidelines available. |
| Geriatric use | No dose adjustment required based on age; monitor renal function closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for RUBRACA (RUBRACA).
| Breastfeeding | No data on rucaparib in human milk or its effects on the breastfed infant. Based on physicochemical properties and animal studies, rucaparib is likely to be excreted in breast milk. The M/P ratio is unknown. Breastfeeding is contraindicated during treatment and for at least 2 weeks after the last dose. |
| Teratogenic Risk | Based on animal studies, rucaparib is embryotoxic and teratogenic. In pregnant rats and rabbits, administration during organogenesis resulted in increased post-implantation loss, reduced fetal body weights, and malformations (including cardiovascular and skeletal defects) at exposures below the recommended human dose. Human pregnancy data are insufficient. The drug should be avoided during all trimesters due to potential harm. |
■ FDA Black Box Warning
Not applicable; rucaparib does not have a boxed warning.
| Serious Effects |
["None (no absolute contraindications listed in FDA labeling)"]
| Precautions | ["Myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) reported in patients receiving PARP inhibitors including rucaparib; monitor for hematologic toxicities","Embryo-fetal toxicity; advise females of reproductive potential of risk to fetus and use effective contraception","Hepatic adverse reactions (elevated liver enzymes); monitor liver function tests monthly during treatment","Hemorrhage (including fatal events) in patients receiving anticoagulation or antiplatelet therapy; caution in patients with bleeding risk"] |
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| Fetal Monitoring | Pregnancy testing is recommended before starting treatment. Women of childbearing potential should use effective contraception during treatment and for at least 6 months after the last dose. Monitor for fetal growth and development if inadvertent exposure occurs; ultrasound surveillance may be considered. |
| Fertility Effects | Based on animal studies, rucaparib may impair fertility. In female rats, ovarian atrophy and reduced corpora lutea were observed at clinically relevant doses. In male rats, testicular degeneration and decreased sperm motility were noted. The reversibility in humans is unknown; advise patients about potential impact on fertility. |