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:
- nausea,
- fatigue (including weakness),
- vomiting,
- anemia,
- abdominal pain,
- changes in taste,
- constipation,
- decreased appetite,
- diarrhea,
- low levels of platelets in the blood (thrombocytopenia),
- shortness of breath,
- dizziness,
- low levels of while blood cells (neutropenia),
- rash,
- fever,
- skin sensitivity to sunlight, and
- itching.
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 SlideshowGet 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 AnswerSIDE 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 reactions | Rubraca N=372 | Placebo N=189 | ||
| Gradesa 1-4 % | Grades 3-4 % | Gradesa 1-4 % | Grades 3-4 % | |
| Gastrointestinal Disorders | ||||
| Nausea | 76 | 4 | 36 | 0.5 |
| Abdominal pain/distentionb | 46 | 3 | 39 | 0.5 |
| Constipation | 37 | 2 | 24 | 1 |
| Vomiting | 37 | 4 | 15 | 1 |
| Diarrhea | 32 | 0.5 | 22 | 1 |
| Stomatitisb | 28 | 1 | 14 | 0.5 |
| General Disorders and Administration Site Conditions | ||||
| Fatigue/asthenia | 73 | 7 | 46 | 3 |
| Skin and Subcutaneous Tissue Disorders | ||||
| Rashb | 43 | 1 | 23 | 0 |
| Nervous System Disorders | ||||
| Dysgeusia | 40 | 0 | 7 | 0 |
| Investigations | ||||
| AST/ALT elevation | 38 | 11 | 4 | 0 |
| Blood and Lymphatic System Disorders | ||||
| Anemia | 39 | 21 | 5 | 0.5 |
| Thrombocytopenia | 29 | 5 | 3 | 0 |
| Neutropenia | 20 | 8 | 5 | 1 |
| Respiratory, Thoracic, and Mediastinal Disorders | ||||
| Nasopharyngitis/Upper respiratory tract infectionb | 29 | 0.3 | 18 | 1 |
| Metabolism and Nutrition Disorders | ||||
| Decreased appetite | 23 | 1 | 14 | 0 |
| 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 Parametera | Rubraca N=372 | Placebo N=189 | ||
| Grade 1-4 % | Grade 3-4 % | Grade 1-4 % | Grade 3-4 % | |
| Chemistry | ||||
| Increase in creatinine | 98 | 0.3 | 90 | 0 |
| Increase in cholesterol | 84 | 4 | 78 | 0 |
| Increase in ALT | 73 | 7 | 4 | 0 |
| Increase in AST | 61 | 1 | 4 | 0 |
| Increase in Alkaline Phosphatase | 37 | 0.3 | 10 | 0 |
| Hematology | ||||
| Decrease in hemoglobin | 88 | 13 | 56 | 1 |
| Decrease in platelets | 44 | 2 | 9 | 0 |
| Decrease in leukocytes | 44 | 3 | 29 | 0 |
| Decrease in neutrophils | 38 | 6 | 22 | 3 |
| Decrease in lymphocytes | 29 | 5 | 20 | 3 |
| 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 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 | ||
| Decreased appetite | 39 | 3 |
| Respiratory, Thoracic, and Mediastinal Disorders | ||
| Dyspnea | 21 | 0.5 |
| 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 Parameter | All Patients with Ovarian Cancer (N = 377) | |
| Grade 1-4 a (%) | Grade 3-4 (%) | |
| Clinical Chemistry | ||
| Increase in creatinine | 92 | 1 |
| Increase in ALTb | 74 | 13 |
| Increase in ASTb | 73 | 5 |
| Increase in cholesterol | 40 | 2 |
| Hematologic | ||
| Decrease in hemoglobin | 67 | 23 |
| Decrease in lymphocytes | 45 | 7 |
| Decrease in platelets | 39 | 6 |
| Decrease in absolute neutrophil count | 35 | 10 |
| 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 Reaction | Rubraca N = 115 | |
| Gradesa 1-4 (%) | Grades 3-4 (%) | |
| General disorders and administration site conditions | ||
| Asthenia/F atigue | 62 | 9 |
| Gastrointestinal disorders | ||
| Nausea | 52 | 3 |
| Constipation | 27 | 1 |
| Vomiting | 22 | 1 |
| Diarrhea | 20 | 0 |
| Blood and lymphatic system disorders | ||
| Anemia | 43 | 25 |
| Thrombocytopeniab | 25 | 10 |
| Metabolism and nutrition disorders | ||
| Decreased appetite | 28 | 2 |
| Skin and subcutaneous tissue disorders | ||
| Rashc | 27 | 2 |
| Investigations | ||
| ALT/AST increased | 33 | 5 |
| 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 Parameter | Rubraca N = 115a | |
| Grade 1-4b(%) | Grade 3-4 (%) | |
| Clinical Chemistry | ||
| Increase in ALTc | 69 | 5 |
| Decrease in phosphate | 68 | 15 |
| Increase in alkaline phosphatase | 44 | 2 |
| Increase in creatinine | 43 | 2 |
| Increase in triglycerides | 42 | 5 |
| Decrease in sodium | 38 | 3 |
| Hematologic | ||
| Decrease in leukocytes | 69 | 5 |
| Decrease in absolute neutrophil count | 62 | 10 |
| Decrease in hemoglobin | 59 | 25 |
| Decrease in lymphocytes | 42 | 17 |
| Decrease in platelets | 40 | 10 |
| 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.