s, interrupt Rubraca 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 Rubraca.
5.2 Embryo-Fetal Toxicity
Rubraca 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 AUC0-24h 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 Rubraca [see Use in Specific Populations (8.1, 8.3) and Clinical Pharmacology (12.1)].
6 ADVERSE REACTIONS
The following serious adverse reactions are discussed elsewhere in the labeling:
Myelodysplastic Syndrome/Acute Myeloid Leukemia [see Warnings and Precautions (5.1)].
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Rubraca 600 mg twice daily as monotherapy, has been studied in 377 patients with ovarian cancer treated in two open-label, single arm trials. In these patients, the median age was 62 years (range 31 to 86), 100% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, 38% had BRCA-mutated ovarian cancer, 45% had received 3 or more prior lines of chemotherapy, and the median time since ovarian cancer diagnosis was 43 months (range 6 to 197).
Adverse reactions led to dose reduction or interruption in 62% of patients, most frequently from anemia (27%), and fatigue/asthenia (22%). Adverse reactions led to dose discontinuation in 10% of patients, most frequently from fatigue/asthenia (2%). The median duration of treatment was 5.5 months (range 0.1 to 28.0).
TABLE 2 and TABLE 3 summarize the common adverse reactions and abnormal laboratory findings, respectively, observed in patients treated with Rubraca.
Table 2. Adverse Reactions Reported in ≥ 20% of Patients with Ovarian Cancer Treated with Rubraca 600 mg Twice Daily
a National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 4.03)
Adverse Reaction All Ovarian Cancer Patients
(N = 377)
%
Gradesa 1-4 Grades 3-4
Gastrointestinal Disorders
Nausea 77 5
Vomiting 46 4
Constipation 40 2
Diarrhea 34 2
Abdominal Pain 32 3
General Disorders
Asthenia/Fatigue 77 11
Blood and Lymphatic System Disorders
Anemia 44 25
Thrombocytopenia 21 5
Nervous System Disorders
Dysgeusia 39 0.3
Metabolism and Nutrition Disorders |
