Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Rubraca: 200 mg [contains fd&c blue #1 aluminum lake, fd&c blue #2 aluminum lake]
Rubraca: 250 mg, 300 mg
Pharmacology
Mechanism of Action
Rucaparib is a poly (ADP-ribose) polymerase (PARP) enzyme inhibitor, including PARP1, PARP2, and PARP3. PARP enzymes are involved in DNA transcription, cell cycle regulation, and DNA repair. By inhibiting PARP, rucaparib may cause increased formation of PARP-DNA complexes, resulting in DNA damage, apoptosis, and cancer cell death. Increased cytotoxicity and anti-tumor activity due to rucaparib was observed in tumor cell lines deficient in BRCA1/2 and other DNA repair genes.
Pharmacokinetics/Pharmacodynamics
Absorption
Cmax is increased by 20%, AUC is increased by 38%, and Tmax is delayed by 2.5 hours following a high-fat meal (as compared to the fasting state)
Distribution
113 to 262 L (following a single IV dose of 12 to 40 mg)
Metabolism
Primarily hepatic via CYP2D6; minor pathways include CYP1A2 and CYP3A4
Time to Peak
1.9 hours
Half-Life Elimination
Terminal: 17 to 19 hours (following a single oral 600 mg dose)
Protein Binding
70%
Use in Specific Populations
Special Populations: Renal Function Impairment
Patients receiving rucaparib 600 mg twice daily with baseline CrCl 60 to 89 mL/minute and those with CrCl between 30 to 59 mL/minute had approximately 15% and 32% higher steady-state AUC, respectively, compared to patients with normal renal function (CrCl 90 mL/minute or above).
Use: Labeled Indications
Ovarian cancer, advanced: Treatment of deleterious germline and/or somatic BRCA mutation associated (as detected by an approved test) ovarian cancer (epithelial, fallopian tube, or primary peritoneal) in patients who have been treated with 2 or more prior lines of chemotherapy.
Ovarian cancer, recurrent (maintenance): Maintenance treatment of recurrent ovarian cancer (epithelial, fallopian tube, or primary peritoneal) in patients who are in complete or partial response to platinum-based chemotherapy.
Contraindications
There are no contraindications listed in the manufacturer's labeling.
Dosage and Administration
Dosing: Adult
Note: Administer only to patients with deleterious germline and/or somatic BRCA mutation, as detected by an approved test. Rucaparib is associated with a moderate emetic potential; antiemetics may be necessary to prevent nausea and vomiting.
Ovarian cancer, advanced: Oral: 600 mg twice daily until disease progression or unacceptable toxicity (Oza 2017; Swisher 2017).
Ovarian cancer, recurrent (maintenance): Oral: 600 mg twice daily until disease progression or unacceptable toxicity (Coleman 2017).
Missed doses: If a dose is missed, administer the next dose at its scheduled time. Do not repeat or replace a vomited dose.
Dosing: Geriatric
Refer to adult dosing.
Dosing: Adjustment for Toxicity
Consider therapy interruption or dose reduction if adverse events occur.
Recommended rucaparib dose reductions:
Starting dose: 600 mg twice daily
1st dose reduction: 500 mg twice daily
2nd dose reduction: 400 mg twice daily
3rd dose reduction: 300 mg twice daily
Secondary myelodysplastic syndrome/acute myeloid leukemia (MDS/AML): Discontinue
Administration
Rucaparib is associated with a moderate emetic potential; antiemetics may be necessary to prevent nausea and vomiting.
Administer orally twice daily (~12 hours apart) with or without food. Do not repeat a vomited dose.
Storage
Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
Drug Interactions
Agomelatine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Agomelatine. Monitor therapy
Alosetron: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Alosetron. Management: Avoid concomitant use of alosetron and moderate CYP1A2 inhibitors whenever possible. If combined use is necessary, monitor for increased alosetron effects/toxicities. Consider therapy modification
ARIPiprazole: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Monitor therapy
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
Bendamustine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Bendamustine. Management: Consider alternatives to moderate CYP1A2 inhibitors during therapy with bendamustine due to the potential for increased bendamustine plasma concentrations and increased bendamustine toxicity. Consider therapy modification
Bromazepam: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Bromazepam. Monitor therapy
Caffeine and Caffeine Containing Products: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Caffeine and Caffeine Containing Products. Monitor therapy
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Monitor therapy
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Avoid combination
ClomiPRAMINE: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of ClomiPRAMINE. Monitor therapy
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy
CloZAPine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of CloZAPine. Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Consider therapy modification
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination
Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. Monitor therapy
DULoxetine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of DULoxetine. Monitor therapy
Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Monitor therapy
Lemborexant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lemborexant. Management: The maximum recommended dosage of lemborexant is 5 mg, no more than once per night, when coadministered with weak CYP3A4 inhibitors. Consider therapy modification
Lomitapide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Consider therapy modification
Melatonin: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Melatonin. Monitor therapy
Mesalamine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy
NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Monitor therapy
OLANZapine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of OLANZapine. Monitor therapy
Pentoxifylline: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Pentoxifylline. Monitor therapy
Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Avoid combination
Pirfenidone: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Pirfenidone. Management: Avoid concomitant use of pirfenidone and moderate CYP1A2 inhibitors whenever possible. If combined, decrease the pirfenidone dose to 1,602 mg per day (534 mg three times daily) and monitor for increased pirfenidone toxicities. Consider therapy modification
Pomalidomide: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Pomalidomide. Monitor therapy
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy
Propranolol: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Propranolol. Monitor therapy
Ramelteon: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Ramelteon. Monitor therapy
Ramosetron: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Ramosetron. Monitor therapy
Rasagiline: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Rasagiline. Management: Limit rasagiline dose to 0.5 mg once daily in patients taking moderate CYP1A2 inhibitors. Consider therapy modification
ROPINIRole: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of ROPINIRole. Monitor therapy
Ropivacaine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Ropivacaine. Monitor therapy
Tasimelteon: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Tasimelteon. Monitor therapy
Theophylline Derivatives: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Theophylline Derivatives. Management: Consider avoidance of this combination. If coadministration is necessary, monitor for increased theophylline serum concentrations and toxicities when combined. Theophylline dose reductions will likely be required. Exceptions: Dyphylline. Consider therapy modification
TiZANidine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of TiZANidine. Management: If combined use cannot be avoided, initiate tizanidine in adults at 2 mg and increase in 2 to 4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Consider therapy modification
Triazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Triazolam. Management: Consider triazolam dose reduction in patients receiving concomitant weak CYP3A4 inhibitors. Consider therapy modification
Ubrogepant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ubrogepant. Management: In patients taking weak CYP3A4 inhibitors, the initial and second dose (if needed) of ubrogepant should be limited to 50 mg. Consider therapy modification
Warfarin: Rucaparib may increase the serum concentration of Warfarin. Monitor therapy
Adverse Reactions
>10%:
Cardiovascular: Peripheral edema (11%)
Central nervous system: Fatigue (≤73%), dizziness (19%) headache (18%), insomnia (15%), depression (11%)
Dermatologic: Skin rash (43%)
Endocrine & metabolic: Increased serum cholesterol (84%)
Gastrointestinal: Nausea (76%), abdominal distention (≤46%), abdominal pain (≤46%), dysgeusia (40%), constipation (37%), vomiting (37%), diarrhea (32%), stomatitis (28%), decreased appetite (23%), dyspepsia (19%)
Hematologic & oncologic: Decreased white blood cell count (44%; grades 3/4: 3%), anemia (39%, grades 3/4: 21%), decreased absolute lymphocyte count (29%, grades 3/4: 5%), thrombocytopenia (29%, grades 3/4: 5%), neutropenia (20%; grades 3/4: 8%)
Hepatic: Increased serum ALT (≤73%), increased serum AST (≤61%), increased serum alkaline phosphatase (37%)
Neuromuscular & skeletal: Weakness (≤73%)
Renal: Increased serum creatinine (98%)
Respiratory: Nasopharyngitis (≤29%), upper respiratory tract infection (≤29%), dyspnea (17%)
Miscellaneous: Fever (13%)
<1%, postmarketing, and/or case reports: Acute myelocytic leukemia, myelodysplastic syndrome
Warnings/Precautions
Concerns related to adverse effects:
- Bone marrow suppression: Anemia, neutropenia, lymphocytopenia, and thrombocytopenia were commonly observed in clinical trials. Monitor blood counts as clinically necessary. Do not initiate treatment until after hematologic recovery (to grade 1 or lower) from prior chemotherapy. Interrupt treatment or reduce the dose for prolonged hematologic toxicity (>4 weeks); monitor blood counts weekly until recovery.
- GI toxicity: Rucaparib is associated with a moderate emetic potential; antiemetics may be needed to prevent nausea and vomiting.
- Secondary malignancy: Myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) has been reported (rarely) in patients receiving rucaparib; may be potentially fatal. Some cases have occurred during or within 28 days following treatment. The duration of therapy prior to diagnosis of MDS/AML ranged from 1 month to ~28 months. The cases were typical of secondary MDS or cancer-therapy related AML and all patients had received prior chemotherapy with platinum agents and/or other DNA-damaging medications. Monitor blood counts (for cytopenia and for clinically significant changes) at baseline and then monthly thereafter. Interrupt treatment and/or reduce the dose for prolonged (>4 weeks) hematological toxicities; monitor blood counts weekly until recovery. If prolonged hematologic toxicity occurs and blood counts do not recover to ≤grade 1 after 4 weeks or if MDS/AML is suspected, further hematology evaluation (including bone marrow and cytogenetic analyses) is necessary. If MDS/AML is confirmed, discontinue therapy.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Other warnings/precautions:
- BRCA-mutation status: Select patients for the treatment of advanced ovarian cancer (not maintenance therapy) based on the presence of deleterious or suspected deleterious BRCA mutations. Information on approved tests for the detection of BRCA mutations may be found at http://www.fda.gov/companiondiagnostics.
Monitoring Parameters
BRCA mutation testing (for treatment of advanced ovarian cancer [not maintenance therapy]); complete blood count at baseline and monthly thereafter, or as clinically indicated (weekly until recovery for prolonged hematologic toxicity); pregnancy test (prior to treatment initiation in females of reproductive potential); monitor for signs/symptoms of MDS/AML. Monitor adherence.
Pregnancy
Pregnancy Considerations
Based on the mechanism of action and data from animal reproduction studies, in utero exposure to rucaparib may cause fetal harm.
Evaluate pregnancy status prior to use in females of reproductive potential. Females of reproductive potential should use effective contraception during therapy and for 6 months after the last rucaparib dose.
Patient Education
What is this drug used for?
- It is used to treat ovarian, fallopian tube, or peritoneal cancer.
Frequently reported side effects of this drug
- Nausea
- Vomiting
- Constipation
- Diarrhea
- Abdominal pain
- Abdominal swelling
- Mouth irritation
- Mouth sores
- Change in taste
- Lack of appetite
- Headache
- Stuffy nose
- Sore throat
- Common cold symptoms
- Trouble sleeping
- Dizziness
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Infection
- Bleeding like vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding
- Swelling of arms or legs
- Depression
- Severe loss of strength and energy
- Weight loss
- Shortness of breath
- Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
