Rubraca

Medical Editor: John P. Cunha, DO, FACOEP Last updated on RxList: 10/13/2021
Rubraca Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

What Is Rubraca?

Rubraca (rucaparib tablets) is a poly (ADP-ribose) polymerase (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. Patients are selected for therapy based on an FDA-approved companion diagnostic for Rubraca.

What Are Side Effects of Rubraca?

Common side effects of Rubraca include:

Dosage for Rubraca

The recommended dose of Rubraca is 600 mg orally twice daily with or without food.

What Drugs, Substances, or Supplements Interact with Rubraca?

Rubraca may interact with other drugs. Tell your doctor all medications and supplements you use.

Rubraca During Pregnancy and Breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant before using Rubracal it may harm a fetus. Pregnancy testing is recommended for females of reproductive potential before starting Rubraca. It is unknown if Rubraca passes into breast milk. Because of the potential for serious adverse reactions in nursing infants, breastfeeding is not recommended while taking Rubraca.

Additional Information

Our Rubraca (rucaparib tablets) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

SLIDESHOW

Signs of Cancer in Women: Symptoms You Can't Ignore See Slideshow
Rubraca Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

  • easy bruising, unusual bleeding (nose, mouth, vagina, or rectum), purple or red pinpoint spots under your skin;
  • blood in your urine;
  • low white blood cell counts--fever, mouth sores, skin sores, sore throat, cough, trouble breathing; or
  • low red blood cells (anemia)--pale skin, unusual tiredness, feeling light-headed or short of breath, cold hands and feet.

Your cancer treatments may be delayed or permanently discontinued if you have certain side effects.

Common side effects may include:

  • low blood cell counts;
  • shortness of breath;
  • cold symptoms such as stuffy nose, sneezing, sore throat;
  • stomach pain, bloating, loss of appetite;
  • nausea, vomiting, diarrhea, constipation;
  • mouth sores, changes in your sense of taste;
  • feeling weak or tired;
  • rash; or
  • abnormal liver function tests.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Rubraca (Rucaparib )

QUESTION

Where does ovarian cancer occur? See Answer
Rubraca Professional Information

SIDE EFFECTS

The following serious adverse reactions are discussed elsewhere in the labeling:

  • Myelodysplastic Syndrome/Acute Myeloid Leukemia [see WARNINGS AND PRECAUTIONS].

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.

The pooled safety population in the WARNINGS AND PRECAUTIONS section reflect exposure to Rubraca at 600 mg BID in 1146 patients in Study10 (CO-338-010), ARIEL2, ARIEL3, and TRITON2.

Maintenance Treatment Of Recurrent Ovarian Cancer

The safety of Rubraca for the maintenance treatment of patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer was investigated in ARIEL3, a randomized (2:1), double-blind, placebo-controlled study in which 561 patients received either Rubraca 600 mg BID (n=372) or placebo (n=189) until disease progression or unacceptable toxicity. The median duration of study treatment was 8.3 months (range: < 1 month to 35 months) for patients who received Rubraca and 5.5 months for patients who received placebo.

Dose interruptions due to an adverse reaction of any grade occurred in 65% of patients receiving Rubraca and 10% of those receiving placebo; dose reductions due to an adverse reaction occurred in 55% of Rubraca patients and 4% of placebo patients. The most frequent adverse reactions leading to dose interruption or dose reduction of Rubraca were thrombocytopenia (18%), anemia (17%), nausea (15%), and fatigue/asthenia (13%). Discontinuation due to adverse reactions occurred in 15% of Rubraca patients and 2% of placebo patients. Specific adverse reactions that most frequently led to discontinuation in patients treated with Rubraca were anemia (3%), thrombocytopenia (3%) and nausea (3%). Table 2 describes the adverse reactions occurring in ≥20% of patients; while Table 3 describes the laboratory abnormalities occurring in ≥25% of patients occurring in ARIEL3.

Table 2: Adverse Reactions in ARIEL3 Occurring in ≥ 20% of Patients

Adverse reactionsRubraca
N=372
Placebo
N=189
Gradesa 1-4 %Grades 3-4 %Gradesa 1-4 %Grades 3-4 %
Gastrointestinal Disorders
Nausea764360.5
Abdominal pain/distentionb463390.5
Constipation372241
Vomiting374151
Diarrhea320.5221
Stomatitisb281140.5
General Disorders and Administration Site Conditions
Fatigue/asthenia737463
Skin and Subcutaneous Tissue Disorders
Rashb431230
Nervous System Disorders
Dysgeusia40070
Investigations
AST/ALT elevation381140
Blood and Lymphatic System Disorders
Anemia392150.5
Thrombocytopenia29530
Neutropenia20851
Respiratory, Thoracic, and Mediastinal Disorders
Nasopharyngitis/Upper respiratory tract infectionb290.3181
Metabolism and Nutrition Disorders
Decreased appetite231140
a National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 4.03)
b Consists of grouped related terms that reflect the medical concept of the adverse reaction

Adverse reactions occurring < 20% of patients treated with Rubraca include headache (18%), dizziness (19%), dyspepsia (19%), insomnia (15%), dyspnea (17%), pyrexia (13%), peripheral edema (11%), and depression (11%).

Table 3: Laboratory Abnormalities in ARIEL3 Occurring in ≥ 25% of Patients

Laboratory ParameteraRubraca
N=372
Placebo
N=189
Grade 1-4 %Grade 3-4 %Grade 1-4 %Grade 3-4 %
Chemistry
Increase in creatinine980.3900
Increase in cholesterol844780
Increase in ALT73740
Increase in AST61140
Increase in Alkaline Phosphatase370.3100
Hematology
Decrease in hemoglobin8813561
Decrease in platelets44290
Decrease in leukocytes443290
Decrease in neutrophils386223
Decrease in lymphocytes295203
a Patients were allowed to enter clinical studies with laboratory values of CTCAE Grade 1.

Treatment Of BRCA-mutated Recurrent Ovarian Cancer After 2 Or More Chemotherapies

Rubraca 600 mg twice daily as monotherapy has also been studied in 377 patients with epithelial ovarian, fallopian tube or primary peritoneal cancer who have progressed after 2 or more prior chemotherapies in two open-label, single arm trials. In these patients, the median age was 62 years (range: 31 to 86), 100% had an 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). Table 4 describes the adverse reactions occurring in ≥20% of patients; while Table 5 describes the laboratory abnormalities occurring in ≥35% of patients occurring in ARIEL2.

Table 4: Adverse Reactions Reported in ≥ 20% of Patients with Ovarian Cancer After ≥ 2 Chemotherapies Treated with Rubraca in Study 10 and ARIEL2

Adverse ReactionAll Ovarian Cancer Patients
(N = 377)
Gradesa 1-4 (%)Grades 3-4 (%)
Gastrointestinal Disorders
Nausea775
Vomiting464
Constipation402
Diarrhea342
Abdominal Pain323
General Disorders
Asthenia/Fatigue7711
Blood and Lymphatic System Disorders
Anemia4425
Thrombocytopenia215
Nervous System Disorders
Dysgeusia390.3
Metabolism and Nutrition Disorders
Decreased appetite393
Respiratory, Thoracic, and Mediastinal Disorders
Dyspnea210.5
a National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 4.03)

The following adverse reactions have been identified in < 20% of the 377 patients treated with Rubraca 600 mg twice daily: dizziness (17%), neutropenia (15%), rash (includes rash, rash erythematous, rash maculopapular and dermatitis) (13%), pyrexia (11%), photosensitivity reaction (10%), pruritus (includes pruritus and pruritus generalized) (9%), hypersensitivity (includes flushing, wheezing, eyelid edema, drug hypersensitivity, face edema, swelling face) (4%), palmar-plantar erythrodysaesthesia syndrome (2%), and febrile neutropenia (1%).

Table 5: Laboratory Abnormalities Reported in ≥ 35% of Patients with Ovarian Cancer After ≥ 2 Chemotherapies Treated with Rubraca in Study 10 and ARIEL2

Laboratory ParameterAll Patients with Ovarian Cancer
(N = 377)
Grade 1-4 a (%)Grade 3-4 (%)
Clinical Chemistry
Increase in creatinine921
Increase in ALTb7413
Increase in ASTb735
Increase in cholesterol402
Hematologic
Decrease in hemoglobin6723
Decrease in lymphocytes457
Decrease in platelets396
Decrease in absolute neutrophil count3510
a At least one worsening shift in CTCAE grade and by maximum shift from baseline.
b Increase in ALT/AST led to treatment discontinuation in 0.3% of patients (1/377).

Treatment Of BRCA-mutated mCRPC After Androgen Receptor-directed Therapy And Chemotherapy

The safety of Rubraca 600 mg twice daily was evaluated in a single arm trial (TRITON2) [see Clinical Studies]. TRITON2 enrolled 209 patients with HRD-positive mCRPC, including 115 with BRCA-mutated mCRPC. Among the patients with BRCA-mutated mCRPC, the median duration of Rubraca treatment was 6.5 months (range 0.5 to 26.7).

There were 2 (1.7%) patients with adverse reactions leading to death, one each attributed to acute respiratory distress syndrome and pneumonia.

Dose interruptions due to an adverse reaction occurred in 57% of patients receiving Rubraca. Adverse reactions requiring dose interruption in >3% of patients included anemia, thrombocytopenia, asthenia/fatigue, nausea, vomiting, neutropenia, ALT/AST increased, creatinine increased, decreased appetite, acute kidney injury, and hypophosphatemia.

Dose reductions due to an adverse reaction occurred in 41% of patients receiving Rubraca. Adverse reactions requiring dose reduction in >3% of patients were anemia (14%), asthenia/fatigue (10%), thrombocytopenia (7%), nausea (6%), decreased appetite (4%), and rash (3%).

Discontinuation due to adverse reactions occurred in 8% of patients receiving Rubraca. None of the adverse reactions leading to discontinuation of Rubraca (ECG QT prolonged, acute respiratory distress syndrome, anemia, balance disorder, cardiac failure, decreased appetite/fatigue/weight decreased, leukopenia/neutropenia, ALT/AST increased, and pneumonia) occurred in more than one patient (<1%).

Tables 6 and 7 summarize the adverse reactions and laboratory abnormalities, respectively, in patients with BRCA-mutated mCRPC in TRITON2.

Table 6: Adverse Reactions Reported in ≥ 20% of Patients with BRCA-mutated mCRPC in TRITON2

Adverse ReactionRubraca
N = 115
Gradesa 1-4 (%)Grades 3-4 (%)
General disorders and administration site conditions
Asthenia/F atigue629
Gastrointestinal disorders
Nausea523
Constipation271
Vomiting221
Diarrhea200
Blood and lymphatic system disorders
Anemia4325
Thrombocytopeniab2510
Metabolism and nutrition disorders
Decreased appetite282
Skin and subcutaneous tissue disorders
Rashc272
Investigations
ALT/AST increased335
a National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 4.03)
b Includes platelet count decreased
cIncludes blister, blood blister, dermatitis, dermatitis contact, eczema, genital rash, palmar-plantar erythrodysaesthesia syndrome, photosensitivity reaction, psoriasis, rash, rash maculo-papular, rash pruritic, skin exfoliation, skin lesion, urticaria

Other clinically relevant adverse reactions that occurred in less than 20% of patients included dyspnea, dizziness, bleeding, urinary tract infection, dysgeusia, dyspepsia, hypersensitivity (including flushing, asthma, choking sensation, periorbital swelling, swelling face, and wheezing), pneumonia, sepsis, ischemic cardiovascular events, renal failure, and venous thromboembolism.

Table 7: Laboratory Abnormalities in ≥ 35% (Grades 1-4) and ≥ 2% (Grades 3-4) Worsening from Baseline in Patients with BRCA-mutated mCRPC in TRITON2

Laboratory ParameterRubraca
N = 115a
Grade 1-4b(%)Grade 3-4 (%)
Clinical Chemistry
Increase in ALTc695
Decrease in phosphate6815
Increase in alkaline phosphatase442
Increase in creatinine432
Increase in triglycerides425
Decrease in sodium383
Hematologic
Decrease in leukocytes695
Decrease in absolute neutrophil count6210
Decrease in hemoglobin5925
Decrease in lymphocytes4217
Decrease in platelets4010
a Denominator for each laboratory parameter is based on the number of patients with a baseline and post-treatment laboratory value available for 111 to 115 patients.
b NCI CTCAE version 5.0; decrease in phosphate is graded using NCI CTACE Version 4.03
c Grade 3-4 ALT or AST elevation led to drug interruption in 4 patients, of which 1 had dose reduction upon rechallenge

Read the entire FDA prescribing information for Rubraca (Rucaparib )

© Rubraca Patient Information is supplied by Cerner Multum, Inc. and Rubraca Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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