Rubraca

Indications and Usage ( 1.2 ) 12/2025 Warnings and Precautions ( 5.1 ) 12/2025

1 INDICATIONS AND USAGE RUBRACA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated: Ovarian cancer for the maintenance treatment of adult patients with a deleterious BRCA mutation (germline and/or somatic)-associated recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. ( 1.1 ) Prostate cancer for the treatment of adult patients with a deleterious BRCA mutation (germline and/or somatic)-associated metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor-directed therapy. Select patients for therapy based on an FDA-approved companion diagnostic for RUBRACA. ( 1.2 , 2.1 ) 1.1 Maintenance Treatment of BRCA -mutated Recurrent Ovarian Cancer RUBRACA is indicated for the maintenance treatment of adult patients with a deleterious BRCA mutation (germline and/or somatic)-associated recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. 1.2 BRCA -mutated Metastatic Castration-Resistant Prostate Cancer RUBRACA is indicated for the treatment of adult patients with a deleterious BRCA mutation (germline and/or somatic)-associated metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor-directed therapy. Select patients for therapy based on an FDA-approved companion diagnostic for RUBRACA [see Dosage and Administration ( 2.1 )].

1.1 Maintenance Treatment of BRCA -mutated Recurrent Ovarian Cancer RUBRACA is indicated for the maintenance treatment of adult patients with a deleterious BRCA mutation (germline and/or somatic)-associated recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.

1.2 BRCA -mutated Metastatic Castration-Resistant Prostate Cancer RUBRACA is indicated for the treatment of adult patients with a deleterious BRCA mutation (germline and/or somatic)-associated metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor-directed therapy. Select patients for therapy based on an FDA-approved companion diagnostic for RUBRACA [see Dosage and Administration ( 2.1 )].

2 DOSAGE AND ADMINISTRATION Recommended dose is 600 mg orally twice daily with or without food. ( 2.2 ) Continue treatment until disease progression or unacceptable toxicity. ( 2.2 ) For adverse reactions, consider interruption of treatment or dose reduction. ( 2.3 ) Patients receiving RUBRACA for mCRPC should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy. ( 2.2 ) 2.1 Patient Selection Maintenance Treatment of BRCA -mutated Recurrent Ovarian Cancer Select patients for the maintenance treatment of recurrent ovarian cancer with RUBRACA based on the presence of a deleterious BRCA mutation (germline and/or somatic) [see Clinical Studies ( 14.1 )]. An FDA-approved test for the detection of deleterious germline and/or somatic BRCA mutations is not currently available. Treatment of BRCA -mutated mCRPC after Androgen Receptor-directed Therapy Select patients for the treatment of mCRPC with RUBRACA based on the presence of a deleterious BRCA mutation (germline and/or somatic) in plasma specimens [see Clinical Studies ( 14.2 )]. A negative result from a plasma specimen does not mean that the patient’s tumor is negative for BRCA mutations. Should the plasma specimen have a negative result, consider performing further genomic testing using tumor specimens as clinically indicated. Information on the FDA-approved tests for the detection of a BRCA mutation in patients with ovarian cancer or with prostate cancer is available at: http://www.fda.gov/CompanionDiagnostics. 2.2 Recommended Dose The recommended dose of Rubraca is 600 mg (two 300 mg tablets) taken orally twice daily with or without food, for a total daily dose of 1,200 mg. ( 2.2 ) Continue treatment until disease progression or unacceptable toxicity. ( 2.2 ) For adverse reactions, consider interruption of treatment or dose reduction. ( 2.3 ) Patients receiving RUBRACA for mCRPC should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy. ( 2.2 ) 2.3 Dose Modifications for Adverse Reactions To manage adverse reactions, consider interruption of treatment or dose reduction. Recommended Rubraca dose modifications for adverse reactions are indicated in Table 1 . Table 1. Recommended Dose Modifications for Adverse Reactions Dose Reduction Dose Starting Dose 600 mg twice daily (two 300 mg tablets) First Dose Reduction 500 mg twice daily (two 250 mg tablets) Second Dose Reduction 400 mg twice daily (two 200 mg tablets) Third Dose Reduction 300 mg twice daily (one 300 mg tablet)

2.1 Patient Selection Maintenance Treatment of BRCA -mutated Recurrent Ovarian Cancer Select patients for the maintenance treatment of recurrent ovarian cancer with RUBRACA based on the presence of a deleterious BRCA mutation (germline and/or somatic) [see Clinical Studies ( 14.1 )]. An FDA-approved test for the detection of deleterious germline and/or somatic BRCA mutations is not currently available. Treatment of BRCA -mutated mCRPC after Androgen Receptor-directed Therapy Select patients for the treatment of mCRPC with RUBRACA based on the presence of a deleterious BRCA mutation (germline and/or somatic) in plasma specimens [see Clinical Studies ( 14.2 )]. A negative result from a plasma specimen does not mean that the patient’s tumor is negative for BRCA mutations. Should the plasma specimen have a negative result, consider performing further genomic testing using tumor specimens as clinically indicated. Information on the FDA-approved tests for the detection of a BRCA mutation in patients with ovarian cancer or with prostate cancer is available at: http://www.fda.gov/CompanionDiagnostics.

2.2 Recommended Dose The recommended dose of Rubraca is 600 mg (two 300 mg tablets) taken orally twice daily with or without food, for a total daily dose of 1,200 mg. ( 2.2 ) Continue treatment until disease progression or unacceptable toxicity. ( 2.2 ) For adverse reactions, consider interruption o …

3 DOSAGE FORMS AND STRENGTHS Tablets (200 mg): blue, round, immediate-release, film-coated, debossed with “C2”. Tablets (250 mg): white, diamond, immediate-release, film-coated, debossed with “C25”. Tablets (300 mg): yellow, oval, immediate-release, film-coated, debossed with “C3”. Tablets: 200 mg, 250 mg, and 300 mg ( 3 )

4 CONTRAINDICATIONS None. None. ( 4 )

6 ADVERSE REACTIONS The following serious adverse reactions are discussed elsewhere in the labeling: Myelodysplastic Syndrome/Acute Myeloid Leukemia [see Warnings and Precautions ( 5.1 )]. Most common adverse reactions (≥10%) among patients with ovarian cancer were nausea, fatigue (including asthenia), anemia, ALT/AST increased, vomiting, diarrhea, decreased appetite, thrombocytopenia, dysgeusia, neutropenia, blood creatinine increased, dyspnea, dizziness, dyspepsia, photosensitivity reaction, and leukopenia. ( 6.1 ) Most common adverse reactions (≥10%) among patients with BRCA -mutated mCRPC were fatigue/asthenia, musculoskeletal pain, nausea, anemia, decreased appetite, increased ALT/AST, constipation, diarrhea, vomiting, thrombocytopenia, dyspnea, increased blood creatinine, edema, dizziness, weight decreased, abdominal pain, dysgeusia, rash, neuropathy peripheral, urinary tract infection, cough, headache, hemorrhage, neutropenia, and photosensitivity reaction. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact pharmaand agent at 1-800-506-8501 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The pooled safety population for patients with ovarian and prostate cancer in the WARNINGS AND PRECAUTIONS section reflect exposure to RUBRACA at 600 mg orally twice daily in 2141 patients treated on clinical trials including ARIEL3, TRITON2, and TRITON3. In ARIEL3 among the patients who received RUBRACA, 57% of patients were exposed for 6 months or longer and 33% were exposed for greater than one year. In TRITON3 among the patients with BRCA-mutated mCRPC who received RUBRACA, 66% were exposed for 6 months or longer and 34% were exposed for greater than one year. In the pooled safety population for patients with ovarian cancer, the most common adverse reactions in ≥ 10% of patients were nausea (68%), asthenia/fatigue (65%), anemia/hemoglobin decreased (45%), AST/ALT increased (39%), vomiting (36%), diarrhea (29%), decreased appetite (27%), thrombocytopenia/platelet count decreased (25%), dysgeusia (24%), neutropenia/neutrophil count decreased (21%), blood creatinine increased (17%), dyspnea (16%), dizziness (14%), dyspepsia (11%), photosensitivity reaction (10%), and leukopenia/white blood cell count decreased (10%). In the pooled safety population for patients with BRCA -mutated mCRPC (N=373) from TRITON2 and TRITON3, the most common adverse reactions in ≥ 10% of patients were fatigue/asthenia (61%), musculoskeletal pain (52%), nausea (52%), anemia/decreased hemoglobin (49%), decreased appetite (35%), increased ALT/AST (31%), constipation (30%), diarrhea (27%), vomiting (26%), thrombocytopenia/decreased platelet count (21%), dyspnea (20%), increased blood creatinine (19%), edema (19%), dizziness (19%), weight decreased (16%), abdominal pain (15%), dysgeusia (15%), rash (13%), neuropathy peripheral (13%), urinary tract infection (13%), cough (12%), headache (12%), hemorrhage (12%), neutropenia/decreased neutrophil count (12%), and photosensitivity reaction (10%). Maintenance Treatment of BRCA -mutated Recurrent Ovarian Cancer The safety of RUBRACA for the maintenance treatment of patients with BRCA -mutated recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer was investigated in ARIEL3, a randomized (2:1), double-blind, placebo-controlled study in which 195 patients with a deleterious BRC A mutation received either RUBRACA 600 mg orally twice daily (n=129) or placebo (n=66) until disease progression or unacceptable toxicity. The median duration of study treatment was 13.6 months (range: < 1 month to 39 months) for patients who received RUBRACA and 5.5 months for patients who received placebo. Dose interruptions due to …

7 DRUG INTERACTIONS 7.1 Effect of Rubraca on Other Drugs Certain CYP1A2, CYP3A, CYP2C9, or CYP2C19 Substrates Concomitant administration of Rubraca with CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates can increase the systemic exposure of these substrates [see Clinical Pharmacology ( 12.3 )] , which may increase the frequency or severity of adverse reactions of these substrates. If concomitant administration is unavoidable between Rubraca and substrates of these enzymes where minimal concentration changes may lead to serious adverse reactions, decrease the substrate dosage in accordance with the approved prescribing information. If concomitant administration with warfarin (a CYP2C9 substrate) cannot be avoided, consider increasing the frequency of international normalized ratio (INR) monitoring.

7.1 Effect of Rubraca on Other Drugs Certain CYP1A2, CYP3A, CYP2C9, or CYP2C19 Substrates Concomitant administration of Rubraca with CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates can increase the systemic exposure of these substrates [see Clinical Pharmacology ( 12.3 )] , which may increase the frequency or severity of adverse reactions of these substrates. If concomitant administration is unavoidable between Rubraca and substrates of these enzymes where minimal concentration changes may lead to serious adverse reactions, decrease the substrate dosage in accordance with the approved prescribing information. If concomitant administration with warfarin (a CYP2C9 substrate) cannot be avoided, consider increasing the frequency of international normalized ratio (INR) monitoring.

Certain CYP1A2, CYP3A, CYP2C9, or CYP2C19 Substrates Concomitant administration of Rubraca with CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates can increase the systemic exposure of these substrates [see Clinical Pharmacology ( 12.3 )] , which may increase the frequency or severity of adverse reactions of these substrates. If concomitant administration is unavoidable between Rubraca and substrates of these enzymes where minimal concentration changes may lead to serious adverse reactions, decrease the substrate dosage in accordance with the approved prescribing information. If concomitant administration with warfarin (a CYP2C9 substrate) cannot be avoided, consider increasing the frequency of international normalized ratio (INR) monitoring.

8 USE IN SPECIFIC POPULATIONS Lactation: Advise women not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action, Rubraca can cause fetal harm when administered to pregnant women. There are no available data in pregnant women to inform the drug-associated risk. In an animal reproduction study, administration of rucaparib to pregnant rats during organogenesis resulted in embryo-fetal death at maternal exposures that were 0.04 times the AUC 0-24h in patients receiving the recommended dose of 600 mg twice daily [see Data] . Apprise pregnant women of the potential risk to a fetus. The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In a dose range-finding embryo-fetal development study, pregnant rats received oral doses of 50, 150, 500, or 1000 mg/kg/day of rucaparib during the period of organogenesis. Post-implantation loss (100% early resorptions) was observed in all animals at doses greater than or equal to 50 mg/kg/day (with maternal systemic exposures approximately 0.04 times the human exposure at the recommended dose based on AUC 0-24h ). 8.2 Lactation Risk Summary There is no information regarding the presence of rucaparib in human milk, or on its effects on milk production or the breast-fed child. Because of the potential for serious adverse reactions in breast-fed children from Rubraca, advise lactating women not to breastfeed during treatment with Rubraca and for 2 weeks following the last dose. 8.3 Females and Males of Reproductive Potential Rubraca can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations ( 8.1 )] . Pregnancy Testing Pregnancy testing is recommended for females of reproductive potential prior to initiating Rubraca. Contraception Females Advise females of reproductive potential to use effective contraception during treatment and for 6 months following the last dose of Rubraca [see Use in Specific Populations ( 8.1 )] . Males Based on findings in genetic toxicity and animal reproduction studies, advise male patients with female partners of reproductive potential or who are pregnant to use effective methods of contraception during treatment and for 3 months following last dose of Rubraca. Advise male patients not to donate sperm during therapy and for 3 months following the last dose of Rubraca [see Use in Specific Populations ( 8.1 ) and Nonclinical Toxicology ( 13.1 )]. 8.4 Pediatric Use The safety and effectiveness of Rubraca in pediatric patients have not been established. 8.5 Geriatric Use Of the 937 patients with ovarian cancer who received Rubraca in clinical trials including ARIEL3, 41% were age 65 or older and 10% were 75 years or older. No major differences in safety were observed between younger and older patients with ovarian cancer. Of the 209 patients with mCRPC who received Rubraca in TRITON2, 77% were age 65 or older and 33% were 75 years or older. No major differences in safety were observed between younger and older patients with mCRPC. 8.6 Renal Impairment No dosage modification is recommended for patients with mild to moderate renal impairment (creatinine clearance [CLcr] between 30 and 89 mL/min, as estimated by the Cockcroft-Gault method) [see Clinical Pharmacology ( 12.3 )]. Rubraca has not been studied in patients with CLcr ULN) [see Clinical Pharmacology ( 12.3 )] . Rubraca has not been studied in patients with severe hepatic impairment (total bilirubin > 3 x ULN and any AST).

12.1 Mechanism of Action Rucaparib is an inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes, including PARP-1, PARP-2, and PARP-3, which play a role in DNA repair. In vitro studies have shown that rucaparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complexes resulting in DNA damage, apoptosis, and cancer cell death. Increased rucaparib-induced cytotoxicity and anti-tumor activity was observed in tumor cell lines with deficiencies in BRCA1/2 and other DNA repair genes. Rucaparib has been shown to decrease tumor growth in mouse xenograft models of human cancer with or without deficiencies in BRCA .

11 DESCRIPTION Rucaparib is an inhibitor of the mammalian polyadenosine 5'-diphosphoribose polymerase (PARP) enzyme. The chemical name is 8-fluoro-2-{4-[(methylamino)methyl]phenyl}-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indol-6-one ((1S,4R)-7,7-dimethyl-2-oxobicyclo[2.2.1]hept-1-yl)methanesulfonic acid salt. The chemical formula of rucaparib camsylate is C 19 H 18 FN 3 O•C 10 H 16 O 4 S and the relative molecular mass is 555.67 Daltons. The chemical structure of rucaparib camsylate is shown below: Rucaparib camsylate is a white to pale yellow powder; formulated into a tablet for oral use. Rucaparib shows pH-independent low solubility of approximately 1 mg/mL across the physiological pH range. Rubraca (rucaparib) tablets contain rucaparib camsylate as the active ingredient. Each 200 mg tablet contains 344 mg rucaparib camsylate equivalent to 200 mg rucaparib free base. Each 250 mg tablet contains 430 mg rucaparib camsylate equivalent to 250 mg rucaparib free base. Each 300 mg tablet contains 516 mg rucaparib camsylate equivalent to 300 mg rucaparib free base. The inactive ingredients in Rubraca tablets include: microcrystalline cellulose, sodium starch glycolate, colloidal silicon dioxide, and magnesium stearate. The cosmetic blue film coating for 200 mg tablets, cosmetic white film coating for 250 mg tablets, and cosmetic yellow film coating for 300 mg tablets is Opadry II containing polyvinyl alcohol, titanium dioxide, polyethylene glycol/macrogol, and talc. The coating is colorized as blue using brilliant blue aluminum lake and indigo carmine aluminum lake, or yellow using yellow iron oxide. 1

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied Rubraca is available as 200 mg, 250 mg, and 300 mg tablets. 200 mg Tablets: Blue, round, and debossed with “C2” on one side Supplied in bottles of 60 tablets (NDC:82154-0783-1) 250 mg Tablets: White, diamond, and debossed with “C25” on one side Supplied in bottles of 60 tablets (NDC:82154-0784-1) 300 mg Tablets: Yellow, oval, and debossed with “C3” on one side Supplied in bottles of 60 tablets (NDC:82154-0785-1) Storage Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [ see USP Controlled Room Temperature ].