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?

Rubraca may cause serious side effects including:

hives,
difficulty breathing,
swelling of your face, lips, tongue, or throat,
easy bruising,
unusual bleeding (nose, mouth, vagina, or rectum),
purple or red pinpoint spots under your skin,
blood in your urine,
fever,
mouth sores,
skin sores,
sore throat,
cough,
pale skin,
unusual tiredness,
lightheadedness,
shortness of breath, and
cold hands and feet

Get medical help right away, if you have any of the symptoms listed above.

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.

Call your doctor at once if you have the following serious side effects:

blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
low levels of sodium in the body with severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady; or
severe nervous system reaction with very stiff (rigid) muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out.

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.

QUESTION

Where does ovarian cancer occur? See Answer

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.

SLIDESHOW

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

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 for patients with ovarian cancer in the WARNINGS AND PRECAUTIONS section reflect exposure to Rubraca at 600 mg orally twice daily in 1594 patients treated on clinical trials including ARIEL3. In this group, 57% of patients were exposed for 6 months or longer and 33% were exposed for greater than one year.

In the pooled safety population for patients with ovarian cancer, the most common adverse reactions in ≥ 10% of patients were nausea (68%), asthenia/fatigue (65%), anemia/hemoglobin decreased (45%), AST/ALT increased (39%), vomiting (36%), diarrhea (29%), decreased appetite (27%), thrombocytopenia/platelet count decreased (25%), dysgeusia (24%), neutropenia/neutrophil count decreased (21%), blood creatinine increased (17%), dyspnea (16%), dizziness (14%), dyspepsia(11%), photosensitivity reaction (10%), and leukopenia/white blood cell count decreased (10%).

Maintenance Treatment Of BRCA-Mutated Recurrent Ovarian Cancer

The safety of Rubraca for the maintenance treatment of patients with BRCA-mutated recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer was investigated in ARIEL3, a randomized (2:1), double-blind, placebo-controlled study in which 195 patients with a deleterious BRCA mutation received either Rubraca 600 mg orally twice daily (n=129) or placebo (n=66) until disease progression or unacceptable toxicity. The median duration of study treatment was 13.6 months (range: < 1 month to 39 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 67% of patients receiving Rubraca and 14% of those receiving placebo; dose reductions due to an adverse reaction occurred in 57% of Rubraca patients and 6% of placebo patients. The most frequent adverse reactions leading to dose interruption or dose reduction of Rubraca were thrombocytopenia (25%), anemia (19%), AST/ALT increased (16%), fatigue/asthenia (14%), and nausea (10%). Discontinuation due to adverse reactions occurred in 15% of Rubraca patients and 5% of placebo patients. Specific adverse reactions that most frequently led to discontinuation in patients treated with Rubraca were thrombocytopenia (4%), nausea (3%), and anemia (2%). 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 Reported in ≥ 20% of Patients with BRCA-mutated Ovarian Cancer in ARIEL3

Adverse reactions	Rubraca N=129		Placebo N=66
Adverse reactions	Grades 1-4^a %	Grades 3-4 %	Grades 1-4^a %	Grades 3-4 %
Gastrointestinal Disorders
Nausea	79	2	29	0
Abdominal pain/distention^b	48	3	49	2
Constipation	39	4	36	2
Vomiting	37	4	14	0
Diarrhea	34	2	18	0
Stomatitis^b	28	0.8	12	0
General Disorders and Administration Site Conditions
Fatigue/asthenia	74	9	52	5
Skin and Subcutaneous Tissue Disorders
Rash^b	45	0	23	0
Nervous System Disorders
Dysgeusia	33	0	6	0
Headache	22	0	15	2
Investigations
AST/ALT elevation	33	16	3	0
Blood and Lymphatic System Disorders
Anemia	41	26	6	0
Thrombocytopenia	35	6	3	0
Neutropenia	22	8	6	0
Respiratory, Thoracic, and Mediastinal Disorders
Nasopharyngitis/Upper respiratory tract infection^b	29	0	20	2
Metabolism and Nutrition Disorders
Decreased appetite	23	2	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 insomnia (19%), dyspnea (17%), dizziness (15%), pyrexia (15%), dyspepsia (12%), peripheral edema (12%), and depression (11%).

Table 3. Laboratory Abnormalities in ≥ 25% of Patients with BRCA-mutated Ovarian Cancer in ARIEL3

Laboratory Parameter^a	Rubraca N=129		Placebo N=66
Laboratory Parameter^a	Grades 1-4^b %	Grades 3-4 %	Grades 1-4^b %	Grades 3-4 %
Chemistry
Increase in creatinine	96	0	89	0
Increase in ALT	67	11	6	0
Increase in AST	59	1	6	0
Increase in cholesterol	39	3	20	0
Increase in Alkaline Phosphatase	39	0	3	0
Hematology
Decrease in hemoglobin	61	18	14	2
Decrease in platelets	47	2	8	0
Decrease in leukocytes	39	3	23	0
Decrease in neutrophils	38	6	18	2
Decrease in lymphocytes	33	7	14	2
^a Patients were allowed to enter clinical studies with laboratory values of CTCAE Grade 1. ^b NCI CTCAE version 4.03.

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 4 and 5 summarize the adverse reactions and laboratory abnormalities, respectively, in patients with BRCA--mutated mCRPC in TRITON2.

Table 4. Adverse Reactions Reported in ≥ 20% of Patients with BRCA-mutated mCRPC in TRITON2

Adverse Reaction	Rubraca N = 115
Adverse Reaction	Grades 1-4^a (%)	Grades 3-4 (%)
General disorders and administration site conditions
Asthenia/Fatigue	62	9
Gastrointestinal disorders
Nausea	52	3
Constipation	27	1
Vomiting	22	1
Diarrhea	20	0
Blood and lymphatic system disorders
Anemia	43	25
Thrombocytopenia^b	25	10
Metabolism and nutrition disorders
Decreased appetite	28	2
Skin and subcutaneous tissue disorders
Rash^c	27	2
Investigations
ALT/AST increased	33	5
^a NCI CTCAE version 4.03. ^b Includes platelet count decreased ^c Includes 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, urticariaf

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, venous thromboembolism, and stomatitis.

Table 5. 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 = 115^a
Laboratory Parameter	Grades 1-4^b (%)	Grades 3-4 (%)
Clinical Chemistry
Increase in ALT^c	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.

DRUG INTERACTIONS

Effect Of Rubraca On Other Drugs

Certain CYP1A2, CYP3A, CYP2C9, Or CYP2C19 Substrates

Concomitant administration of Rubraca with CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates can increase the systemic exposure of these substrates [see CLINICAL PHARMACOLOGY], which may increase the frequency or severity of adverse reactions of these substrates. If concomitant administration is unavoidable between Rubraca and substrates of these enzymes where minimal concentration changes may lead to serious adverse reactions, decrease the substrate dosage in accordance with the approved prescribing information.

If concomitant administration with warfarin (a CYP2C9 substrate) cannot be avoided, consider increasing the frequency of international normalized ratio (INR) monitoring.

Read the entire FDA prescribing information for Rubraca (Rucaparib )