rucaparib (Rx)

Brand and Other Names:Rubraca
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 200mg
  • 250mg
  • 300mg

Ovarian Cancer

Recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer

  • Indicated for maintenance treatment of recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in adults who are in a complete or partial response to platinum-based chemotherapy
  • 600 mg PO BID
  • Continue until disease progression or unacceptable toxicity

Advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer

  • Indicated for treatment of adults with a deleterious BRCA mutation (germline and/or somatic)-associated epithelial ovarian, fallopian tube, or primary peritoneal cancer who have been treated with ≥2 chemotherapies
  • 600 mg PO BID
  • Continue until disease progression or unacceptable toxicity

Prostate Cancer

Indicated for treatment of adults with a deleterious BRCA mutation (germline and/or somatic)-associated metastatic castration-resistant prostate cancer (mCRPC) previously treated with androgen receptor-directed therapy and a taxane-based chemotherapy

600 mg PO BID

Continue until disease progression or unacceptable toxicity

Should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy

Dosage Modifications

Consider treatment interruption or dosage reduction in the event of adverse reactions

Recommended dose reductions

  • First dose reduction: 500 mg BID (two 250-mg tablets)
  • Second dose reduction: 400 mg BID (two 200-mg tablets)
  • Third dose reduction: 300 mg qDay (one 300-mg tablet)

Hepatic impairment

  • Mild (total bilirubin ≤ULN and AST >ULN, or total bilirubin between 1-1.5x ULN and any AST): No dose adjustment required
  • Moderate-to-severe (total bilirubin >1.5x ULN): Lack of data; no recommendation available

Renal impairment

  • Mild-to-moderate (CrCl 30-89): No dose adjustment required
  • Severe (CrCl <30 mL/min) or patients on dialysis: Lack of data; no recommendation available

Dosing Considerations

Patient selection

  • BRCA-mutated advanced ovarian cancer or mCRPC: Select patients based on presence of a deleterious BRCA mutation (germline and/or somatic)
  • mCRPC: If plasma specimen result is negative, consider performing further genomic testing using tumor specimens as clinically indicated; a negative plasma specimen does not indicate that a tumor is negative for BRCA mutation
  • Information on the FDA-approved test is available at: http://www.fda.gov/CompanionDiagnostics

Safety and efficacy not established

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Interactions

Interaction Checker

and rucaparib

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            >10% (All Grades)

            Recurrent ovarian cancer

            • Increased creatinine (98%)
            • Decreased hemoglobin (88%)
            • Increased cholesterol (84%)
            • Nausea (76%)
            • Fatigue/asthenia (73%)
            • Increased ALT (73%)
            • Increased AST (61%)
            • Abdominal pain/distention (46%)
            • Decreased platelets (44%)
            • Decreased leukocytes (44%)
            • Rash (43%)
            • Dysgeusia (40%)
            • Anemia (39%)
            • AST/ALT elevation (38%)
            • Decreased neutrophils (38%)
            • Constipation (37%)
            • Vomiting (37%)
            • Increased alkaline phosphatase (37%)
            • Diarrhea (32%)
            • Thrombocytopenia (29%)
            • Decreased lymphocytes (29%)
            • Nasopharyngitis/upper respiratory tract infection (29%)
            • Stomatitis (28%)
            • Decreased appetite (23%)
            • Neutropenia (20%)
            • Dizziness (19%)
            • Dyspepsia (19%)
            • Headache (18%)
            • Dyspnea (17%)
            • Insomnia (15%)
            • Pyrexia (13%)
            • Peripheral edema (11%)
            • Depression (11%)

            BRCA-mutated advanced ovarian cancer

            • Increased creatinine (98%)
            • Increased ALT (74%)
            • Increased AST (73%)
            • Nausea (77%)
            • Asthenia/fatigue (77%)
            • Decreased hemoglobin (67%)
            • Vomiting (46%)
            • Decreased lymphocytes (45%)
            • Anemia (44%)
            • Constipation (40%)
            • Increased cholesterol (40%)
            • Decreased platelets (39%)
            • Dysgeusia (39%)
            • Decreased appetite (39%)
            • Decreased ANC (35%)
            • Diarrhea (34%)
            • Abdominal Pain (32%)
            • Thrombocytopenia (21%)
            • Dyspnea (21%)
            • Dizziness (17%)
            • Neutropenia (15%)
            • Rash (13%)
            • Pyrexia (11%)

            mCRPC

            • Increased ALT (69%)
            • Decreased leukocytes (69%)
            • Decreased phosphate (68%)
            • Asthenia/fatigue (62%)
            • Decreased ANC (62%)
            • Decreased hemoglobin (59%)
            • Nausea (52%)
            • Increased alkaline phosphatase (44%)
            • Increased creatinine (43%)
            • Anemia (43%)
            • Decreased lymphocytes (42%)
            • Increased triglycerides (42%)
            • Decreased platelets (40%)
            • Decreased sodium (38%)
            • ALT/AST increased (33%)
            • Decreased appetite (28%)
            • Constipation (27%)
            • Rash (27%)
            • Thrombocytopenia (25%)
            • Vomiting (22%)
            • Diarrhea (20%)
            • <20%
              • Dyspnea
              • Dizziness
              • Bleeding
              • Urinary tract infection
              • Dysgeusia
              • Dyspepsia
              • Hypersensitivity (including flushing, asthma, choking sensation, periorbital swelling, swelling face, and wheezing)
              • Pneumonia
              • Sepsis
              • Ischemic cardiovascular events
              • Renal failure
              • Venous thromboembolism

            >10% (Grade 3 or 4)

            Recurrent ovarian cancer

            • Anemia (21%)
            • Decreased hemoglobin (13%)
            • AST/ALT elevation (11%)

            BRCA-mutated advanced ovarian cancer

            • Anemia (25%)
            • Decreased hemoglobin (23%)
            • Asthenia/fatigue (11%)

            mCRPC

            • Anemia (25%)

            1-10% (Grade 3 or 4)

            Recurrent ovarian cancer

            • Neutropenia (8%)
            • Fatigue/asthenia (7%)
            • Increased ALT (7%)
            • Decreased neutrophils (6%)
            • Decreased lymphocytes (5%)
            • Thrombocytopenia (5%)
            • Nausea (4%)
            • Vomiting (4%)
            • Increased cholesterol (4%)
            • Abdominal pain/distention (3%)
            • Decreased leukocytes (3%)
            • Decreased platelets (2%)
            • Constipation (2%)
            • Stomatitis (1%)
            • Rash (1%)
            • Decreased appetite (1%)
            • Increased AST (1%)

            BRCA-mutated advanced ovarian cancer

            • Photosensitivity reaction (10%)
            • Decreased ANC (10%)
            • Pruritus (9%)
            • Decreased lymphocytes (7%)
            • Decreased platelets (6%)
            • Thrombocytopenia (5%)
            • Nausea (5%)
            • Vomiting (4%)
            • Hypersensitivity (4%)
            • Decreased appetite (3%)
            • Abdominal pain (3%)
            • Constipation (2%)
            • Diarrhea (2%)
            • Palmoplantar erythrodysesthesia syndrome (2%)
            • Febrile neutropenia (1%)

            mCRPC

            • Thrombocytopenia (10%)
            • Asthenia/Fatigue (9%)
            • ALT/AST increased (5%)
            • Nausea (3%)
            • Rash (2%)
            • Decreased appetite (2%)
            • Constipation (1%)
            • Vomiting (1%)

            <1% (Grade 3 or 4)

            Recurrent ovarian cancer

            • Diarrhea (0.5%)
            • Nasopharyngitis/upper respiratory tract infection (0.3%)

            BRCA-mutated advanced ovarian cancer

            • Dyspnea (0.5%)
            • Dysgeusia (0.3%)
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            Warnings

            Contraindications

            None

            Cautions

            Rare reports of myelodysplastic syndrome/acute myeloid leukemia; evaluate CBC at baseline and monthly thereafter; do not initiate until patients recover from hematological toxicities caused by previous chemotherapy (ie, grade ≤1)

            Not recommended in patients with neutrophil counts <1000 cells/mm3; consider alternative therapy when treating patients with neutropenia and acute bacterial skin and skin structure infections

            Increases susceptibility to sunburn; advise to use appropriate sun protection

            Based on its mechanism of action, can cause fetal harm

            Drug interaction overview

            • Rucaparib inhibits CYP1A2, CYP3A, CYP2C9, and CYP2C19
            • Adjust dosage of CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates, if clinically indicated
            • If coadministration with warfarin (a CYP2C9 substrate) cannot be avoided, consider increasing frequency of INR monitoring
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            Pregnancy

            Pregnancy

            Based on findings from animal studies and its mechanism of action, can cause fetal harm when administered to pregnant women

            There are no available data in pregnant women to inform the drug-associated risk

            Pregnancy testing recommended for females of reproductive potential before initiating

            Contraception

            • Females of reproductive potential: Use effective contraception during treatment and for 6 months following the final dose
            • Males with female partners of reproductive potential: Use effective contraception during treatment and for 3 months following the final dose
            • Sperm donation: Do not donate sperm during treatment and for 3 months following the final dose

            Animal studies

            • Administration to pregnant rats during organogenesis resulted in embryofetal death at maternal exposure that were 0.04 times the AUC in patients receiving 600 mg BID

            Lactation

            Unknown if distributed in human breast milk

            Advise women not to breastfeed during treatment and for 2 weeks after the final dose

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            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 cell death

            Increased rucaparib-induced cytotoxicity 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

            Absorption

            Absolute bioavailability: 36% (range: 30-45%)

            Peak plasma time: 1.9 hr

            Steady-state peak plasma concentration: 1940 ng/mL

            AUC: 16,900 hr⋅ng/mL

            After high-fat meal (compared with fasting): Peak plasma concentration increased by 20%; AUC increased by 38%; peak plasma time delayed by 2.5 hr

            Distribution

            Vd: 113-262 L

            Protein bound: 70%

            Metabolism

            Metabolized (in vitro) primarily by CYP2D6 and to a lesser extent by CYP1A2 and CYP3A4

            Elimination

            Half-life: 17-19 hr

            Clearance: 15.30-79.2 L/hr

            Pharmacogenomics

            Steady-state concentrations following 600 mg BID did not differ significantly across CYP2D6 or CYP1A2 genotype subgroups

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            Administration

            Oral Administration

            May administer with or without food

            Missed/vomited dose: Skip missed dose and take next dose at its scheduled time (ie, do not take an extra dose); vomited doses should not be replaced

            Storage

            Store at controlled room temperature 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F)

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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.