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Rubraca

Generic Name: Rucaparib Camsylate
Class: Antineoplastic Agents
Molecular Formula: C19H18FN3O
CAS Number: 283173-50-2

Introduction

Rucaparib camsylate, a poly (ADP-ribose) polymerase (PARP) inhibitor, is an antineoplastic agent.

Uses for Rubraca

Rucaparib camsylate has the following uses:

Rucaparib camsylate is a PARP inhibitor indicated as monotherapy for the treatment of patients with deleterious BRCA mutation (germline and/or somatic) associated advanced ovarian cancer who have been treated with two or more chemotherapies. Select patients for therapy based on an FDA-approved companion diagnostic for rucaparib camsylate.1

This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.1

Rubraca Dosage and Administration

General

Rucaparib camsylate is available in the following dosage form(s) and strength(s):

Tablets: 200 mg and 300 mg1

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

  • Recommended dose is 600 mg orally twice daily with or without food.1

  • Continue treatment until disease progression or unacceptable toxicity.1

  • For adverse reactions, consider interruption of treatment or dose reduction.1

Cautions for Rubraca

Contraindications

None.1

Warnings/Precautions

Myelodysplastic Syndrome/Acute Myeloid Leukemia

Myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) was reported in 2 of 377 (0.5%) patients with ovarian cancer treated with rucaparib camsylate. The duration of rucaparib camsylate treatment prior to the diagnosis of MDS/AML was 57 days and 539 days. Both patients received prior treatment with platinum and other DNA damaging agents.1

In addition, AML was reported in 2 (<1%) patients with ovarian cancer enrolled in a blinded, randomized trial evaluating rucaparib camsylate versus placebo. One case of AML was fatal. The duration of treatment prior to the diagnosis of AML was 107 days and 427 days. Both patients had received prior treatment with platinum and other DNA damaging agents.1

Monitor complete blood count testing at baseline and monthly thereafter. Do not start rucaparib camsylate until patients have recovered from hematological toxicity caused by previous chemotherapy (≤grade 1). For prolonged hematological toxicities, interrupt rucaparib camsylate and monitor blood counts weekly until recovery. If the levels have not recovered to grade 1 or less after 4 weeks, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. If MDS/AML is confirmed, discontinue rucaparib camsylate.1

Embryo-fetal Toxicity

Rucaparib camsylate can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings from animal studies. In an animal reproduction study, administration of rucaparib to pregnant rats during organogenesis resulted in embryo-fetal death at maternal exposure that were 0.04 times the AUC in patients receiving the recommended dose of 600 mg twice daily. Apprise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for 6 months following the last dose of rucaparib camsylate.1

Specific Populations

Pregnancy

Based on findings from animal studies and its mechanism of action, rucaparib camsylate 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 exposure that were 0.04 times the AUC0-24h in patients receiving the recommended dose of 600 mg twice daily. Apprise pregnant women of the potential risk to a fetus.1

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.1

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 AUC0-24h).1

Lactation

There is no information regarding the presence of rucaparib in human milk, or on its effects on milk production or the breast-fed infant. Because of the potential for serious adverse reactions in breast-fed infants from rucaparib camsylate, advise lactating women not to breastfeed during treatment with rucaparib camsylate and for 2 weeks after the final dose.1

Females and Males of Reproductive Potential

Pregnancy testing is recommended for females of reproductive potential prior to initiating rucaparib camsylate.1

Rucaparib camsylate can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment and for 6 months following the final dose of rucaparib camsylate. 1

Pediatric Use

The safety and effectiveness of rucaparib camsylate in pediatric patients have not been established.1

Geriatric Use

One hundred and sixty (42%) of the 377 ovarian cancer patients in clinical trials of rucaparib camsylate were 65 years of age or older. No overall differences in safety were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out. The effectiveness of rucaparib camsylate in patients with BRCA-mutant ovarian cancer who were 65 years of age or older could not be assessed due to the small number of patients (N=38).1

Hepatic Impairment

No starting dose adjustment is recommended for patients with mild hepatic impairment (total bilirubin less than or equal to upper limit of normal [ULN] and AST greater than ULN, or total bilirubin between 1.0 to 1.5 times ULN and any AST). No recommendation of starting dose adjustment is available for patients with moderate to severe hepatic impairment (total bilirubin greater than 1.5 times ULN) due to a lack of data.1

Renal Impairment

No starting dose adjustment 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). There is no recommended starting dose for patients with CLcr less than 30 mL/min or patients on dialysis due to a lack of data.1

Common Adverse Effects

  • Most common adverse reactions (≥20%) were nausea, fatigue (including asthenia), vomiting, anemia, abdominal pain, dysgeusia, constipation, decreased appetite, diarrhea, thrombocytopenia, and dyspnea.1

  • Most common laboratory abnormalities (≥35%) were increase in creatinine, increase in ALT, increase in AST, decrease in hemoglobin, decrease in lymphocytes, increase in cholesterol, decrease in platelets, and decrease in absolute neutrophil count.1

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Please see product labeling for drug interaction information.

Actions

Mechanism of Action

Rucaparib is an inhibitor of 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.1

Advice to Patients

Advise the patient to read the FDA-approved patient labeling (Patient Information).1

MDS/AML

Advise patients to contact their healthcare provider if they experience weakness, feeling tired, fever, weight loss, frequent infections, bruising, bleeding easily, breathlessness, blood in urine or stool, and/or laboratory findings of low blood cell counts, or a need for blood transfusions. These may be signs of hematological toxicity or a more serious uncommon bone marrow problem called 'myelodysplastic syndrome' (MDS) or 'acute myeloid leukemia' (AML) which have been reported in patients treated with rucaparib camsylate.1

Embryo-Fetal Toxicity

Advise females to inform their healthcare provider if they are pregnant or become pregnant. Inform female patients of the risk to a fetus and potential loss of the pregnancy.1 Advise females of reproductive potential to use effective contraception during treatment and for 6 months after receiving the last dose of rucaparib camsylate.1

Photosensitivity

Advise patients to use appropriate sun protection due to the increased susceptibility to sunburn while taking rucaparib camsylate.1

Lactation

Advise females not to breastfeed during treatment and for 2 weeks after the last dose of rucaparib camsylate.1

Dosing Instructions

Instruct patients to take rucaparib camsylate orally twice daily with or without food. Doses should be taken approximately 12 hours apart. Advise patients that if a dose of rucaparib camsylate is missed or if the patient vomits after taking a dose of rucaparib camsylate, patients should not take an extra dose, but take the next dose at the regular time.1

Additional Information

AHFS First Release. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Rucaparib Camsylate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablet, Film Coated

200 mg

Rubraca

Clovis Oncology Inc.

300 mg

Rubraca

Clovis Oncology Inc.

AHFS Drug Information. © Copyright 2017, Selected Revisions January 6, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

References

1. Clovis Oncology, Inc. Rubraca (rucaparib) ORAL prescribing information. 2016 Dec.

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