Rucaparib (Rubraca) inhibits PARP enzymes (poly ADP-ribose polymerase) that play an essential role in cell replication. It is used in the treatment of advanced or recurrent ovarian cancer.

Rucaparib Uses:

• Advanced Ovarian cancer:

  • It is used in the treatment of deleterious germline and/or somatic BRCA mutations associated ovarian cancer (epithelial, fallopian tube, or primary peritoneal) in patients who have been treated with two or more chemotherapy regimens before.
  • Note: The mutations should be detected by approved labs

• Maintenance treatment of recurrent ovarian cancer:

  • It is used in the maintenance treatment of recurrent ovarian cancer (epithelial, fallopian tube, or primary peritoneal) in patients who have a complete or partial response to platinum-based chemotherapy.

Rucaparib (Rubraca) Dose in Adults

Note:

• It should be administered only to patients with deleterious germline and/or somatic BRCA mutation, as detected by an approved test.
• Premedication with an antiemetic drug may be advised to prevent nausea and vomiting associated with the drug.

Rucaparib (Rubraca) Dose in the treatment of advanced ovarian cancer:

• Oral: 600 mg twice daily until disease either disease progression or unacceptable toxicity.

Rucaparib (Rubraca) Dose in the maintenance treatment of recurrent ovarian cancer:

• Oral: 600 mg twice daily until either disease progression or unacceptable toxicity.

• Missed doses:

  • In case a dose is missed, the next dose should be administered at the scheduled time. if the dose is followed by vomiting, it should not be repeated.

Use in Children:

Not indicated.

Pregnancy Risk Category: D

• Pregnancy may be a time when the drug can cause harm to the fetus.
• Before treatment is initiated, it is important to perform a pregnancy test on any females with reproductive potential. 
• Effective contraception should be used for the duration of therapy and at least six months thereafter to prevent any potential pregnancy.

Use while breastfeeding

• It is unknown if the drug will be excreted into breastmilk.
• Because of possible adverse effects on the infant's health, the manufacturer suggests that you stop breastfeeding during treatment and for at least two weeks thereafter.

Dose in Kidney Disease:

• CrCl ≥30 mL/minute at baseline:
  • No dosage adjustment is necessary
• CrCl <30 mL/minute:
  • There are no dosage adjustments provided in the manufacturer’s labeling (it has not been studied).
• Hemodialysis:
  • There are no dosage adjustments provided in the manufacturer’s labeling (it has not been studied).

Dose in Liver disease:

• 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 (it has not been studied).

Common Side Effects of Rucaparib (Rubraca):

• Cardiovascular:

  • Peripheral Edema

• Central Nervous System:

  • Fatigue
  • Dizziness Headache
  • Insomnia
  • Depression

• Dermatologic:

  • Skin Rash

• Endocrine & Metabolic:

  • Increased Serum Cholesterol

• Gastrointestinal:

  • Nausea
  • Abdominal Distention
  • Abdominal Pain
  • Dysgeusia
  • Constipation
  • Vomiting
  • Diarrhea
  • Stomatitis
  • Decreased Appetite
  • Dyspepsia

• Hematologic & Oncologic:

  • Decreased White Blood Cell Count
  • Anemia
  • Decreased Absolute Lymphocyte Count
  • Thrombocytopenia
  • Neutropenia

• Hepatic:

  • Increased Serum ALT
  • Increased Serum AST
  • Increased Serum Alkaline Phosphatase

• Neuromuscular & Skeletal:

  • Weakness

• Renal:

  • Increased Serum Creatinine

• Respiratory:

  • Nasopharyngitis
  • Upper Respiratory Tract Infection
  • Dyspnea

• Miscellaneous:

  • Fever

Contraindication to Rucaparib (Rubraca):

The manufacturer's labeling does not list any contraindications.

Warnings and precautions

• Suppression of bone marrow
  • Cytopenias are a risk for patients (Anemia and neutropenia as well as lymphocytopenia and thrombocytopenia).
  • The treatment should be stopped until the blood counts improve.
  • Patients with prolonged hematologic toxicities (exceeding 4 week) should have their treatment stopped or reduced. Until recovery, blood counts must be monitored regularly.
• Toxicity to the gastrointestinal tract:
  • The moderate risk of vomiting is associated with treatment. Patients may need antiemetics to prevent nausea or vomiting.
• Secondary malignancy
  • Rarely, secondary hematological malignancies like MDS or acute myeloid leukemia have been reported in patients receiving rucaparib therapy. These conditions could prove fatal.
  • Sometimes, secondary malignancies can develop within the first 28 days after treatment. Secondary malignancies can develop in as little as one month, up to as long at 28 months.
  • Patients who had developed secondary malignancies reported that they had received chemotherapy with DNA-damaging drugs and platinum-based chemotherapy. These patients displayed classic features of secondary malignancies.
  • Monitoring blood counts is crucial at baseline, and again periodically or as indicated by a physician. 
  • The patient should stop receiving treatment if they experience blood-related side effects. This should continue for at least four weeks until their hematologic toxicities improve to baseline. 
  • The blood counts should also be checked frequently during this period.
  • If the patient's hematologic toxicity persists for more than 4 weeks, or if there is suspicion of MDS or AML, a thorough hematologic evaluation including bone marrow biopsy or cytogenetics may help. If MDS or AML are suspected, treatment should be stopped immediately.

Rucaparib: Drug Interaction

Monitoring parameters:

• BRCA mutation testing is recommended to treat advanced ovarian carcinoma (not for maintenance therapy).
• Complete blood count prior to treatment, and every month thereafter, unless otherwise indicated clinically.
• CBC should always be checked weekly after prolonged hematologic toxicity.
• Before treatment is initiated in females with reproductive potential, a pregnancy test should be done
• Monitor for symptoms and signs of MDS/AML.
• Monitoring drug adherence.

How to administer Rucaparib?

• It is generally taken twice daily, with or without meals. 
• It can cause mild vomiting. Premedication with antiemetic medications may be necessary to prevent nausea and vomiting.
• It is not recommended to repeat a dose if it is thrown out.

Mechanism of action of Rucaparib:

• Rucaparib is an ADP-ribose polymerase enzyme inhibitor (PARP enzyme inhibit), which includes PARP1, PARP2, PARP3, and PARP3.
• PARP enzymes play an important role in DNA transcription, cell cycle regulation and DNA repair. PARP-DNA complexes can be formed when PARP enzymes have been inhibited.
• This results in DNA damage, apoptosis and death of cancer cells. In tumor cells lacking BRCA1/2 or other DNA repair genes, increased cytotoxicity and antitumor activity were seen.

Absorption:

• The drug's C-max is increased 20% and AUC by 38% respectively. T-max is delayed 2.5 hours after eating a high-fat food (in comparison to fasting).

Protein binding:

• 70%

Metabolism:

• It is metabolized primarily in the liver via CYP2D6;
• minor pathways include CYP1A2 and CYP3A4

Bioavailability:

• 36% (range: 30% to 45%)

Half-life elimination:

• Terminal half-life elimination after a single oral dose of 600 mg dose is 17 to 19 hours.

Time to peak:

• 1.9 hours

International Brand names of Rucaparib:

• Rubraca

Rucaparib Brand Names in Pakistan:

No Brands Available in Pakistan.