rucaparib (Rx)

Brand and Other Names:Rubraca
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 200mg
  • 250mg
  • 300mg

Ovarian Cancer

Indicated as monotherapy for patients with deleterious BRCA mutation (germline and/or somatic) associated with advanced ovarian cancer who have been treated with ≥2 chemotherapies

Also, indicated for the maintenance treatment of recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy

Initial dose: 600 mg (two 300 mg tablets) PO BID

Continue treatment until disease progression or unacceptable toxicity

See also Administration

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 ≤upper limit of normal [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

  • Select patients for treatment based on the presence of a deleterious BRCA mutation (germline and/or somatic)
  • Information on the FDA-approved test for the detection of a tumor BRCA mutation in patients with ovarian cancer is available at: http://www.fda.gov/CompanionDiagnostics

Safety and efficacy not established

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Adverse Effects

Adverse effects listed are for all grades (ie, 1-4) unless otherwise stated

>10%

Increased creatinine (98%)

Decreased hemoglobin (88%)

Increased cholesterol (84%)

Nausea (76-77%)

Asthenia/fatigue (73-77%)

Increased AST/ALT (38-73%)

Vomiting (46%)

Abdominal pain/distension (46%)

Decreased lymphocytes (45%)

Decreased platelets (44%)

Decreased leukocytes (44%)

Anemia (39-44%)

Rash (43%)

Constipation (37-40%)

Decreased appetite (23-39%)

Decreased neutrophils (38%)

Increased alkaline phosphatase (37%)

Dysgeusia (40%)

Decreased ANC (35%)

Diarrhea (32%)

Abdominal pain (32%)

Thrombocytopenia (21-29%)

Decreased lymphocytes (29%)

Nasopharyngitis/upper respiratory tract infection (29%)

Stomatitis (28%)

Anemia, grades 3-4 (21%)

Dyspnea (21%)

Neutropenia (20%)

Dizziness (17%)

Decreased hemoglobin, grades 3-4 (13%)

Increased AST/ALT, grades 3-4 (1-11%)

Pyrexia (11%)

1-10%

Photosensitivity (10%)

Decreased ANC, grades 3-4 (10%)

Pruritus (9%)

Decreased lymphocytes, grades 3-4 (7%)

Asthenia/fatigue, grades 3-4 (7%)

Decreased neutrophils, grades 3-4 (6%)

Decreased lymphocytes, grades 3-4 (6%)

Thrombocytopenia, grades 3-4 (5%)

Vomiting, grades 3-4 (4%)

Increased cholesterol, grades 3-4 (4%)

Nausea, grades 3-4 (4%)

Abdominal pain, grades 3-4 (3%)

Decreased appetite, grades 3-4 (3%)

Decreased leukocytes, grades 3-4 (3%)

Palmar-plantar erythrodysesthesia syndrome (2%)

Constipation, grades 3-4 (2%)

Diarrhea, grades 3-4 (2%)

Decreased platelets, grades 3-4 (2%)

Febrile neutropenia (1%)

<1%

Dyspnea, grades 3-4 (0.5%)

Dysgeusia, grades 3-4 (0.3%)

Increased creatinine, grades 3-4 (0.3%)

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Warnings

Contraindications

None

Cautions

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

Increases susceptibility to sunburn; advise patients to use appropriate sun protection

Based on its mechanism of action, can cause fetal harm (see Pregnancy)

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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

Advise women to use effective contraception during treatment and for 6 months following the final dose

Animal studies

  • Administration to pregnant rats during organogenesis resulted in embryo-fetal 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

Because of the potential for serious adverse reactions in breastfed infants, 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: Instruct patients to take the 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.

To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

Adding plans allows you to:

  • View the formulary and any restrictions for each plan.
  • Manage and view all your plans together – even plans in different states.
  • Compare formulary status to other drugs in the same class.
  • Access your plan list on any device – mobile or desktop.

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.