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Rucaparib

Medically reviewed on September 10, 2018

Pronunciation

(roo KAP a rib)

Index Terms

  • AG014699
  • CO-338
  • PF-01367338
  • PF-01367338 BW
  • Rucaparib Camsylate

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

Brand Names: U.S.

  • Rubraca

Pharmacologic Category

  • Antineoplastic Agent, PARP Inhibitor

Pharmacology

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.

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%

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.

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: Renal Impairment

CrCl ≥30 mL/minute: No dosage adjustment is necessary

CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Hemodialysis: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Dosing: Hepatic Impairment

Mild impairment (total bilirubin ≤ ULN and AST > ULN or total bilirubin 1 to 1.5 times ULN and any AST): No dosage adjustment is necessary.

Moderate to severe impairment (total bilirubin > 1.5 times ULN): There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

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. Avoid combination

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

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Monitor therapy

Cilostazol: CYP2C19 Inhibitors may increase the serum concentration of Cilostazol. Management: Consider reducing the cilostazol dose to 50 mg twice daily in patients who are also receiving inhibitors of CYP2C19. Consider therapy modification

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

CYP1A2 Substrates (High risk with Inhibitors): CYP1A2 Inhibitors (Moderate) may decrease the metabolism of CYP1A2 Substrates (High risk with Inhibitors). Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Avoid combination

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

Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Monitor therapy

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

NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. 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: Use any such combination with caution and close monitoring for pirfenidone toxicity. Avoid the use of pirfenidone with moderate CYP1A2 inhibitors whenever CYP2C9, 2C19, 2C6, or 2E1 is also inhibited (either by the CYP1A2 inhibitor or by a third drug). Consider therapy modification

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Rasagiline: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Rasagiline. 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

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 Considerations

Based on animal reproduction studies and its mechanism of action, rucaparib may be expected to cause adverse events to the fetus. Females of reproductive potential should use effective contraception during therapy and for 6 months after the last dose. Pregnancy testing is recommended prior to therapy initiation in females of reproductive potential.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience nausea, vomiting, constipation, diarrhea, abdominal pain, abdominal edema, mouth irritation, mouth sores, change in taste, lack of appetite, headache, rhinitis, pharyngitis, common cold symptoms, insomnia, or dizziness. Have patient report immediately to prescriber signs of infection, signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; hematuria; 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, or shortness of breath (HCAHPS).

• Educate patient about signs of a significant reaction (eg, 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. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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