rucaparib

High Alert

Maintenance treatment of recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who have experienced a complete or partial response to platinum-based chemotherapy.
Deleterious BRCA mutation-associated metastatic, castration-resistant prostate cancer in patients who have been treated with androgen-receptor directed therapy and a taxane-based chemotherapy regimen.

Action ⬆ ⬇

Acts as a poly (ADP-ribose) polymerase (PARP) inhibitor, thereby disrupting DNA transcription, cell cycle regulation and DNA repair.

Therapeutic effects:

Decreased growth and spread of epithelial ovarian, fallopian tube, primary peritoneal, or prostate cancer.

Pharmacokinetics ⬆ ⬇

Absorption: 30–45% absorbed following oral administration; bioavailability increased but delayed with high-fat meal.

Distribution: Extensively distributed to tissues.

Metabolism/Excretion: Extensively metabolized primarily by the CYP2D6 isoenzyme and to a lesser extent by the CYP1A2 and CYP3A4 isoenzymes; information regarding mode of elimination unknown.

Half-Life: 17–19 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	2 hr	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Severe hepatic impairment;
Severe renal impairment or dialysis;
Rep: Women of reproductive potential and men with female partners of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

Derm: photosensitivity, rash, palmar-plantar erythrodysaesthesia syndrome, pruritus

Endo: hypercholesterolemia

GI: ↓appetite, ↑liver function tests, abdominal pain, constipation, diarrhea, nausea, vomiting

GU: ↑serum creatinine

Hemat: anemia, lymphocytopenia, neutropenia, thrombocytopenia, MYELODYSPLASTIC SYNDROME/ACUTE MYELOID LEUKEMIA

Neuro: dizziness, dysgeusia, fatigue

Resp: dyspnea

Misc: fever

Interactions ⬆ ⬇

Drug-drug:

May ↑ levels and toxicity of CYP1A2 substrates, CYP2C9 substrates, CYP2C19 substrates, and CYP3A substrates; if concurrent administration unavoidable, consider ↓ dose of CYP1A2, CYP2C9, CYP2C19, or CYP3A substrate; if concurrent administration with warfarin unavoidable, monitor INR more frequently.

Route/Dosage ⬆ ⬇

PO (Adults ): 600 mg twice daily until disease progression or unacceptable toxicity.

Availability ⬆ ⬇

Tablets: 200 mg; 250 mg; 300 mg

Assessment ⬆ ⬇

Monitor for signs and symptoms of myelodysplastic syndrome/acute myeloid leukemia during therapy. May require discontinuation of therapy.

Lab Test Considerations:

Select patients for maintenance treatment of recurrent ovarian cancer or for maintenance treatment of recurrent ovarian cancer based on the presence of a deleterious BRCA mutation (germline and/or somatic). For patient selection for BRCA-mutated ovarian cancer, 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.Verify negative pregnancy test prior to starting therapy.Monitor CBC prior to and monthly during therapy. Do not start rucaparib until hematologic toxicity from previous chemotherapy has recovered to ≤Grade 1. For prolonged hematologic toxicities, interrupt rucaparib and monitor CBC weekly until recovery. If levels have not recovered to ≤Grade 1 after 4 wk, refer patient to hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. If myelodysplastic syndrome/acute myeloid leukemia is confirmed, discontinue rucaparib.
- May cause anemia, thrombocytopenia, lymphocytopenia, and neutropenia.
- May cause ↑ serum creatinine, ALT, AST, and cholesterol.

Implementation ⬆ ⬇

Patients receiving rucaparib for metastatic, castration-resistant prostate cancer should also receive a gonadotropin-releasing hormone analog concurrently or should have had bilateral orchiectomy.
Recommended Dose Modifications for Adverse Reactions: Starting dose: 600 mg twice daily. 1st dose reduction: 500 mg twice daily. 2nd dose reduction: 400 mg twice daily. 3rd dose reduction: 300 mg twice daily.
PO: Administer 2 tablets twice daily approximately 12 hr apart, without regard to food.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take rucaparib as directed. If a dose is missed, omit and take next dose at scheduled time. Do not replace vomited doses.
Advise patient to notify health care professional if signs and symptoms of myelodysplastic syndrome/acute myeloid leukemia (weakness, feeling tired, fever, weight loss, frequent infections, bruising, bleeding easily, breathlessness, blood in urine or stool) occur.
Advise patient to wear protective clothing and sunscreen to prevent photosensitivity reactions.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception during and for 6 mo following last dose of rucaparib and to avoid breastfeeding during and for 2 wk after last dose. Advise males with female partners of reproductive potential to use effective contraception during and for 3 mo after last dose. Advise males to avoid donating sperm during therapy and for 3 mo after last dose.

Evaluation/Desired Outcomes ⬆ ⬇

Decrease in growth and spread of ovarian, fallopian tube, primary peritoneal, or prostate cancer.

US Brand Names ⬆ ⬇

Code ⬆

NDC Code

69660- Clovis Oncology, Inc.
- 69660-201- Rubraca
  - 69660-201-91- 60 TABLET, FILM COATED in 1 BOTTLE (69660-201-91)

69660- Clovis Oncology, Inc.
- 69660-202- Rubraca
  - 69660-202-91- 60 TABLET, FILM COATED in 1 BOTTLE (69660-202-91)

69660- Clovis Oncology, Inc.
- 69660-203- Rubraca
  - 69660-203-91- 60 TABLET, FILM COATED in 1 BOTTLE (69660-203-91)

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇