Rucaparib Camsylate

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

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

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

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

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

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

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

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

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.

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

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.

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.