BDPARIB Rucaparib Tablets 300mg

[Drug Name]

Generic Name: Rucaparib Tablets

Brand Name: Rubraca, BDPARIB

English Name: Rucaparib Tablets

Pinyin: Lúkǎpǎlì Piàn

Specification: 300 mg/tablet; 60 tablets/box

Manufacturer: BDR Pharmaceuticals Internationals Pvt Ltd.

[Composition]

Active Ingredient: Rucaparib

Chemical Name: 8-fluoro-2-{4-[(methylamino)methyl]phenyl}-1,3,4,5-tetrahydro-6H-pyrano[4,3,2-de]quinolin-5-one

Molecular Formula: C19H18FN3O

Molecular Weight: 323.36

[Indications]

Rucaparib is a poly (ADP-ribose) polymerase (PARP) inhibitor.

1. Ovarian Cancer:

First-line maintenance treatment: For adult patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer associated with homologous recombination deficiency (HRD) positivity who have achieved a complete response (CR) or partial response (PR) to platinum-based chemotherapy. 

HRD positivity is defined as: having a deleterious or suspected deleterious BRCA gene mutation, and/or a genomic instability score (GIS) meeting a preset threshold.

Second-line or later maintenance treatment: For adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who have achieved a complete response (CR) or partial response (PR) to platinum-based chemotherapy.

Monotherapy: For the treatment of adult patients with advanced ovarian cancer harboring a deleterious or suspected deleterious germline or somatic BRCA gene mutation who have previously received two or more lines of chemotherapy.

2. Prostate Cancer:

Treatment: For the treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC) harboring a deleterious or suspected deleterious BRCA gene mutation (germline and/or somatic) who have previously received androgen receptor-directed therapy and taxane-based chemotherapy. 【Dosage and Administration】

Recommended dosage: 600 mg (i.e., two 300 mg tablets) taken orally twice daily (once in the morning and once in the evening), for a total daily dose of 1200 mg.

Administration: May be taken with or without food. Tablets should be swallowed whole; do not chew, crush, or break them. If a dose is missed or vomiting occurs, do not take a replacement dose; take the next dose at the scheduled time.

Duration of treatment: For maintenance therapy, treatment should continue until disease progression, unacceptable toxicity, or completion of a maximum of 2 years of treatment (please follow specific medical advice). In the treatment setting, therapy should continue until disease progression or unacceptable toxicity occurs.

Dose adjustments: To manage adverse reactions, treatment interruption, dose reduction, or permanent discontinuation may be required. 

First dose reduction: 500 mg (one 250 mg tablet + one tablet—combination depends on available strengths; typically two 250 mg tablets), twice daily. 

Second dose reduction: 400 mg (one 200 mg tablet + one tablet—combination depends on available strengths), twice daily. 

Third dose reduction: 300 mg (one 300 mg tablet), twice daily. 

If the patient cannot tolerate the 300 mg twice-daily dose, treatment should be permanently discontinued.

【Adverse Reactions】

The most common adverse reactions (incidence ≥ 20%) and laboratory abnormalities associated with rucaparib include:

Very common (≥ 1/10):

Gastrointestinal reactions: Nausea, vomiting, diarrhea, constipation, abdominal pain, decreased appetite. 

Hematologic abnormalities: Anemia, thrombocytopenia, neutropenia, lymphopenia. 

Systemic reactions: Fatigue/lethargy, asthenia. 

Liver function abnormalities: Increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST). 

Other: Dysgeusia (taste disturbance), rash, dyspnea. Serious adverse reactions include:

Myelodysplastic syndrome/acute myeloid leukemia (MDS/AML): MDS/AML has been reported in patients treated with rucaparib in clinical trials; some cases were fatal. Monitor complete blood counts (CBC) periodically before and during treatment. Discontinue rucaparib permanently if MDS/AML is confirmed.

Hematologic toxicities: Including anemia, thrombocytopenia, and neutropenia. Monitor CBC monthly during the first 3 months of treatment and periodically thereafter. Interrupt treatment, reduce dosage, or administer blood transfusions as necessary.

【Contraindications】

Patients with a history of severe hypersensitivity to rucaparib or any of its excipients.

Pregnant and lactating women (see [Use in Pregnant and Lactating Women] for details).

【Precautions】

1.  Risk of MDS/AML: This is a class-wide "black box warning" for PARP inhibitors. Physicians and patients should be fully aware of this risk and remain vigilant.

2.  Hematologic monitoring: Regular monitoring of complete blood counts (CBC) is required during treatment. Tests should be performed at baseline, monthly during the first 3 months of treatment, and subsequently at the start of each treatment cycle or as clinically indicated.

3.  Embryo-fetal toxicity: Based on its mechanism of action, rucaparib may cause fetal harm when administered to pregnant women. Women of reproductive potential must use effective contraception during treatment and for 6 months after the last dose.

4.  Impact on male fertility: Based on animal studies, rucaparib may impair male fertility. Sperm preservation should be discussed with male patients.

5.  Hepatic and renal impairment: No dose adjustment is required for patients with mild to moderate hepatic impairment or mild renal impairment. Data on use in patients with moderate to severe renal impairment or severe hepatic impairment are limited; use with caution.

【Drug Interactions】

CYP enzyme effects: Rucaparib is a moderate inhibitor of CYP1A2, CYP2C9, CYP2C19, and CYP3A. Caution should be exercised when co-administering with drugs that have a narrow therapeutic index and are metabolized by these enzymes (e.g., theophylline, S-warfarin, phenytoin, clozapine); monitoring of the efficacy or plasma concentrations of these drugs should be considered.

P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) substrates: Rucaparib may increase exposure to drugs such as digoxin and rosuvastatin; caution is advised during co-administration, and dose reduction of these drugs should be considered.

Gastric acid-modulating agents: Co-administration with proton pump inhibitors (e.g., omeprazole), H2-receptor antagonists, or antacids may reduce plasma concentrations of rucaparib. Staggered administration is recommended (e.g., taking rucaparib at least 2 hours before or 2 hours after taking antacids).

【Pharmacology and Toxicology】

Pharmacological action: Rucaparib is a small-molecule inhibitor of PARP (including PARP-1, PARP-2, and PARP-3). PARP enzymes play a key role in DNA repair. In tumor cells with homologous recombination repair (HRR) deficiencies (such as BRCA mutations), inhibiting PARP simultaneously blocks two major DNA damage repair pathways (base excision repair and homologous recombination repair), leading to the accumulation of DNA double-strand breaks and cell death—a concept known as "synthetic lethality."

Toxicological studies:

Genotoxicity: Positive results in in vitro and in vivo assays. 

Reproductive toxicity: Animal studies indicate embryo-fetal toxicity. Male fertility may be impaired.

【Pharmacokinetics】

Absorption: Time to peak concentration (Tmax) after oral administration is approximately 1.9 hours. High-fat food delays absorption but does not affect overall exposure.

Distribution: Large apparent volume of distribution; plasma protein binding is approximately 70%.

Metabolism: Primarily metabolized in the liver via multiple pathways, including CYP2D6, CYP1A2, CYP2C9, CYP2C19, and CYP3A4. Excretion: Primarily excreted via feces (70.2%) and to a lesser extent via urine (18.8%); the terminal half-life (t1/2) is approximately 25–30 hours.

[Storage]

Store at room temperature (20°C to 25°C). Short-term storage between 15°C and 30°C is permitted.

Keep in the original packaging and protect from moisture.

Important Note: This information is intended to provide a comprehensive medical reference and is not a substitute for professional medical advice. Please consult your attending physician regarding your specific medical condition, treatment plan, and any questions you may have.

Specifications

Product Name: Rucaparib Tablets 300mg (60 tablets/box)

Common Name: Rucaparib Tablets

Active Ingredient: Rucaparib

Dosage Form: Tablets

Specification: 300mg/tablet; 60 tablets/box

Manufacturer: BDR Pharmaceuticals Internationals Pvt Ltd.

Indications: Rucaparib is a poly (ADP-ribose) polymerase (PARP) inhibitor.

1. Ovarian Cancer:

First-line maintenance treatment: For adult patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer associated with homologous recombination deficiency (HRD) positivity who have achieved a complete response (CR) or partial response (PR) to platinum-based chemotherapy.

HRD positivity is defined as: presence of a deleterious or suspected deleterious BRCA gene mutation and/or a genomic instability score (GIS) meeting the predefined threshold.

Second-line or later maintenance treatment: For adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who have achieved a complete response (CR) or partial response (PR) to platinum-based chemotherapy.

Monotherapy: For the treatment of adult patients with advanced ovarian cancer harboring a deleterious or suspected deleterious germline or somatic BRCA gene mutation who have previously received two or more lines of chemotherapy. 2. Prostate Cancer:

Indication: For the treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC) harboring deleterious or suspected deleterious BRCA gene mutations (germline and/or somatic) who have previously received androgen receptor-directed therapy and taxane-based chemotherapy.

Dosage and Administration: Recommended dose: 600 mg (i.e., two 300 mg tablets) orally twice daily (once in the morning and once in the evening), for a total daily dose of 1200 mg.

Administration: May be taken with or without food. Tablets should be swallowed whole; do not chew, crush, or break them. If a dose is missed or vomiting occurs, do not take a replacement dose; take the next dose at the scheduled time.

Duration of Treatment: Treatment should continue until disease progression, unacceptable toxicity, or completion of a maximum of 2 years of therapy (please follow specific medical advice). In the treatment setting, therapy should continue until disease progression or unacceptable toxicity occurs.

Dose Modification: Management of adverse reactions may require treatment interruption, dose reduction, or permanent discontinuation.

First dose reduction: 500 mg (one 250 mg tablet + one tablet of appropriate strength—usually two 250 mg tablets), twice daily.

Second dose reduction: 400 mg (one 200 mg tablet + one tablet of appropriate strength), twice daily.

Third dose reduction: 300 mg (one 300 mg tablet), twice daily.

If the patient cannot tolerate the 300 mg twice-daily dose, treatment should be permanently discontinued.