Lucaparib brand contains Rucaparib is an orally available poly (ADP-ribose) polymerase (PARP) inhibitor used in the treatment of certain types of ovarian, prostate, and other cancers. It is designed to exploit deficiencies in DNA repair mechanisms, particularly in patients with BRCA1/BRCA2 mutations and other homologous recombination deficiencies (HRD). 

Mechanism of Action

Rucaparib works by inhibiting PARP enzymes (PARP-1, PARP-2, and PARP-3), which are involved in DNA repair through the base excision repair pathway. By blocking these enzymes, rucaparib prevents the repair of single-strand DNA breaks, leading to the accumulation of double-strand breaks.

• In patients with BRCA mutations or HRD, where DNA repair is already compromised, rucaparib induces synthetic lethality, resulting in cancer cell death.
• This mechanism is particularly effective in ovarian and prostate cancers that rely on PARP-mediated DNA repair pathways.

Rucaparib is a promising PARP inhibitor that has demonstrated effectiveness in ovarian and prostate cancers, particularly in patients with BRCA mutations. Its mechanism of action makes it a valuable option for patients with homologous recombination deficiency (HRD).

Indications and FDA Approvals

1. Ovarian Cancer

• Maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy.
• Treatment of BRCA-mutated ovarian cancer in patients who have received two or more lines of chemotherapy.

2. Prostate Cancer

• Rucaparib is approved for metastatic castration-resistant prostate cancer (mCRPC) in patients with BRCA1/2 mutations who have received prior androgen receptor-directed therapy and chemotherapy.

3. Other Potential Uses (Under Investigation)

• Clinical trials are evaluating its efficacy in breast cancer, pancreatic cancer, and other solid tumors with HRD or BRCA mutations.

However, due to potential side effects such as bone marrow suppression, liver toxicity, and secondary cancers, regular monitoring and dose modifications are crucial. With ongoing clinical trials exploring additional indications, rucaparib may expand its role in precision oncology. For patients with platinum-sensitive ovarian cancer or mCRPC, rucaparib provides a targeted, oral treatment option that helps delay disease progression and improve outcomes.

Dosage and Administration

• The recommended dose of Rucaparib is 600 mg taken orally twice or thrice daily, with or without food as prescribed by the Physician.
• Treatment should continue until disease progression or unacceptable toxicity occurs.
• Dose adjustments may be required based on side effects and patient tolerance.

Side Effects of Rucaparib

Common Side Effects

• Nausea and vomiting
• Fatigue
• Decreased appetite
• Abdominal pain
• Diarrhea or constipation
• Anemia
• Increased liver enzyme levels (ALT/AST)
• Dysgeusia (altered taste)

Serious Side Effects

• Myelodysplastic Syndrome (MDS) / Acute Myeloid Leukemia (AML): Rare but potentially life-threatening conditions that require close monitoring.
• Severe bone marrow suppression: Including thrombocytopenia (low platelets) and neutropenia (low neutrophils).
• Liver toxicity: Regular liver function tests are advised.
• Pneumonitis (lung inflammation): Rare but serious side effect requiring discontinuation of treatment.

Warnings and Precautions

1. Hematologic Toxicity

• Monitor complete blood counts (CBCs) monthly for signs of anemia, neutropenia, or thrombocytopenia.

2. Secondary Cancers (MDS/AML)

• Patients should be monitored for signs of unexplained bleeding, infection, or persistent fatigue.

3. Liver Function Monitoring

• Regular assessment of ALT, AST, and bilirubin levels is necessary due to the risk of hepatotoxicity.

4. Pregnancy and Fertility Risks

• Rucaparib can cause fetal harm; hence, pregnant women should not take this medication.
• Effective contraception is required during treatment and for 6 months after discontinuation.
• Male patients with female partners of reproductive potential should use contraception during and for 3 months post-treatment.

Drug Interactions

Rucaparib is metabolized mainly by CYP enzymes (CYP2C19, CYP3A4), so caution is needed when co-administering with drugs that:

• Increase CYP activity (reduce rucaparib effectiveness): Rifampin, St. John’s Wort.
• Inhibit CYP activity (increase toxicity risk): Ketoconazole, Clarithromycin.

Patients should inform their healthcare providers about all medications and supplements they are taking to avoid adverse interactions.

Pharmacokinetics

• Absorption: Rapidly absorbed after oral administration.
• Time to peak plasma levels: 1.5 to 3 hours post-dose.
• Metabolism: Primarily via CYP2C19 and CYP3A4 enzymes in the liver.
• Half-life: Approximately 17-19 hours, allowing twice-daily dosing.
• Excretion: Mostly in feces (55%) and urine (44%).