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Rucaparib

Pronunciation

(roo KAP a rib)

Index Terms

  • AG014699
  • CO-338
  • PF-01367338
  • PF-01367338 BW
  • Rubraca
  • 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: 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 cell death. Increased cytotoxicity 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 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 (monotherapy) of deleterious germline and/or somatic BRCA mutation associated (as detected by an approved test) advanced ovarian cancer in patients who have been treated with 2 or more prior lines of 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.

Ovarian cancer, advanced: Oral: 600 mg twice daily until disease progression or unacceptable toxicity.

Missed doses: If a dose is missed, administer the next dose at its scheduled time. Do not repeat 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

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

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. 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

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

Adverse Reactions

>10%:

Central nervous system: Fatigue (≤77%), dizziness (17%)

Dermatologic: Skin rash (13%)

Endocrine & metabolic: Increased serum cholesterol (40%)

Gastrointestinal: Nausea (77%), vomiting (46%), constipation (40%), decreased appetite (39%), dysgeusia (39%), diarrhea (34%), abdominal pain (32%)

Hematologic & oncologic: Decreased hemoglobin (67%, grades 3 to 4: 23%), decreased absolute lymphocyte count (45%, grades 3 to 4: 7%), anemia (44%, grades 3 to 4: 25%), thrombocytopenia (21%, grades 3 to 4: 5%), neutropenia (15%)

Hepatic: Increased serum ALT (74%), increased serum AST (73%)

Neuromuscular & skeletal: Weakness (≤77%)

Renal: Increased serum creatinine (92%)

Respiratory: Dyspnea (21%)

Miscellaneous: Fever (11%)

1% to 10%:

Dermatologic: Skin photosensitivity (10%), pruritus (9%), palmar-plantar erythrodysesthesia (2%)

Hematologic & oncologic: Febrile neutropenia (1%)

<1% (Limited to important or life-threatening): 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. Prolonged hematologic toxicity may require therapy interruption. ·

• Gastrointestinal toxicity: Nausea and vomiting may commonly occur.

• Secondary malignancy: Myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) and AML have been reported (rarely) in a clinical trial of patients with ovarian cancer receiving rucaparib monotherapy. The duration of therapy prior to development of MDS/AML and AML ranged from 57 days to ~1.5 years and 107 days to 427 days, respectively; all patients had received prior chemotherapy with platinum agents and/or other DNA-damaging medications. Monitor blood counts at baseline and then monthly and as clinically indicated. If prolonged hematologic toxicity occurs and blood counts do not recover to ≤ grade 1 after 4 weeks, further evaluation (including bone marrow and cytogenetic analyses) is necessary. If MDS/AML is confirmed, discontinue therapy.

Monitoring Parameters

Complete blood count at baseline and monthly thereafter, or as clinically indicated (weekly until recovery for prolonged hematologic toxicity); monitor for signs/symptoms of MDS/AML

Pregnancy Considerations

Based on animal reproduction studies and its mechanism of action, rucaparib may be expected to cause adverse events to the fetus. Women 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.

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, change in taste, lack of appetite, 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), 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.

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