Niraparib NIRANIB 100mg

Chinese Name: Niraparib

Brand Name: Niranib

Dosage/Specification: 100 mg/capsule; 30 capsules/bottle

Manufacturer: Everest Pharmaceuticals (Bangladesh)

Indications:

This product is indicated for the treatment of recurrent epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer that has responded to platinum-based chemotherapy.

Dosage and Administration:

Dosage and administration instructions may vary depending on the specific dosage form and strength of the product; please consult the specific package insert for usage instructions or follow your physician's orders.

1. The recommended dose is 300 mg, taken once daily. It may be taken either on an empty stomach or with food. The capsules should be swallowed whole at the same time each day. Taking the medication at bedtime may help reduce the incidence of nausea. Treatment with this product should be initiated within 8 weeks after the completion of the platinum-based chemotherapy regimen. If a dose is missed or if vomiting occurs after taking the medication, do not take a replacement dose; simply take the next scheduled dose at the regularly appointed time.

2. If a Grade ≥3 non-hematologic adverse reaction occurs, suspend treatment. If the adverse reaction resolves within 28 days, resume treatment at a reduced dose of 200 mg. If a Grade ≥3 non-hematologic adverse reaction recurs at this reduced dose, suspend treatment again. If the adverse reaction resolves within 28 days, resume treatment at a further reduced dose of 100 mg. If a Grade ≥3 non-hematologic adverse reaction recurs at this dose, or if the adverse reaction does not resolve within 28 days, discontinue the medication permanently.

3. Upon the first occurrence of a platelet count <100,000/µL or a hemoglobin level <9 g/dL, reduce the dose to 200 mg and resume treatment. If the aforementioned conditions recur, suspend treatment. If the neutrophil count recovers to >1,000/µL or the hemoglobin level recovers to >9 g/dL within 28 days, reduce the dose to 100 mg and resume treatment. If the neutrophil count fails to recover to >1000/μL or hemoglobin to >9 g/dL within 28 days, or if the neutrophil count remains <1000/μL or hemoglobin <8 g/dL while on a 100 mg dose, the drug should be permanently discontinued.

5. If the platelet count falls to ≤10,000/μL, platelet transfusion should be considered; if the patient is concomitantly taking antiplatelet agents or anticoagulants, discontinuation of these concomitant medications—or the transfusion of a higher dose of platelets—should be considered.

Adverse Reactions:

1. Serious adverse reactions include myelodysplastic syndrome and/or acute lymphocytic leukemia, myelosuppression, and cardiotoxicity.

2. Common adverse reactions include thrombocytopenia, anemia, neutropenia, leukopenia, palpitations, nausea, constipation, vomiting, abdominal pain, oral mucositis, diarrhea, dyspepsia, dry mouth, fatigue, decreased appetite, urinary tract infection, elevated ALT and/or AST, myalgia, back pain, arthralgia, headache, dizziness, sensory disturbances, insomnia, anxiety, nasopharyngitis, dyspnea, cough, rash, hypertension, and decreased hemoglobin levels.

3. Uncommon adverse reactions include tachycardia, peripheral edema, hypokalemia, bronchitis, conjunctivitis, elevated GGT, elevated serum creatinine, elevated alkaline phosphatase, weight loss, depression, and epistaxis.

Contraindications:

1. Contraindicated in pregnant women.

2. It is unknown whether this drug is excreted in human milk; given the potential for serious adverse reactions, nursing mothers should discontinue breastfeeding until at least one month after the completion of treatment.

3. The safety and efficacy of this drug in pediatric patients have not been established.

4. No dose adjustment is required for patients with mild to moderate renal impairment; the safety and efficacy of this drug in patients with severe renal impairment or end-stage renal disease have not been established.

5. No dose adjustment is required for patients with mild hepatic impairment; the safety of this drug in patients with moderate to severe hepatic impairment has not been established. Precautions:

1. This product may cause Myelodysplastic Syndrome (MDS) (please verify the disease terminology) and/or Acute Lymphocytic Leukemia (ALL); in severe cases, these conditions may be fatal. If any of the aforementioned diseases are diagnosed, the medication should be discontinued immediately.

2. This product may cause bone marrow suppression. During the first month of treatment, a complete blood cell count should be monitored weekly; thereafter, monitoring should be performed monthly, or at any time clinically indicated.

3. This product may cause hypertension, or even hypertensive crisis. During the first year of treatment, blood pressure and heart rate should be monitored monthly; thereafter, periodic monitoring should be performed. Patients with coronary insufficiency, arrhythmias, or pre-existing hypertension require particularly close monitoring; patients with hypertension may require adjustments to the dosage of their antihypertensive medications.

4. This product is embryotoxic. Women of childbearing potential must employ effective contraceptive measures during treatment and for at least 6 months following the completion of treatment.

Drug Interactions:

No formal drug interaction studies have been conducted. Following the administration of the recommended oral dose, neither this product nor its metabolites were found to have any effect on the CYP system, nor are they substrates for P-glycoprotein.

Pharmacological Action:

This product is an inhibitor of PARP enzymes, including PARP1, PARP2, and PARP3. PARP enzymes are involved in maintaining cellular homeostasis—specifically processes such as DNA transcription, cell cycle regulation, and DNA repair. By inhibiting PARP activity, this product promotes the formation of PARP-DNA complexes, thereby disrupting cellular homeostasis and ultimately leading to cell death.

Pharmacokinetics:

1. Absorption: Following a single oral dose of 300 mg of this product, the maximum plasma concentration (Cmax) was 804 (±403) ng/mL. Within the dose range of 30 to 400 mg, both the Area Under the Curve (AUC) and Cmax were proportional to the dose. After 21 days of oral administration, the accumulation ratio was approximately 2-fold. The oral bioavailability of this product is approximately 73%, with peak plasma concentrations reached at approximately 3 hours. The absorption of this product is not affected by a high-fat meal.

2. Distribution: The apparent volume of distribution is 1220 (±1114) L. In a specific study, the apparent volume of distribution in patients with tumors was found to be approximately 1074 L. The protein binding rate is 83%. 3. Metabolism: This product is primarily metabolized by carboxylesterases into inactive metabolites; these metabolites undergo further metabolism via glucuronidation.

4. Elimination: Following multiple doses of 300 mg of this product, the mean elimination half-life (t½) is 36 hours. The mean clearance rate in oncology patients is 16.2 L/hour. After administration of radiolabeled product, 47.5% (range: 33.4%–60.2%) of the radioactivity was recovered in urine and 38.8% (range: 28.3%–47.0%) in feces within 21 days. The recovered amounts of the unchanged drug in urine and feces accounted for 11% and 19% of the administered dose, respectively.

Storage:

Store at 20–25°C; excursions between 15–30°C are permitted for short periods.

Product Specifications

Product Name: Niraparib Capsules (Zele / NIRANIB) 100 mg × 30 Capsules

Common Name: Niraparib Capsules

Active Ingredient: Niraparib

Dosage Form: Capsules

Specification: 100 mg/capsule; 30 capsules/bottle

Manufacturer: Everest Pharmaceuticals (Bangladesh)

Indications: This product is indicated for the treatment of recurrent epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer that has responded to platinum-based chemotherapy.

Dosage and Administration: Dosage and administration instructions may vary depending on the specific dosage form and strength of the product; please refer to the specific package insert for usage instructions or follow your physician's advice.

1. The recommended dose is 300 mg, taken once daily. It may be taken either on an empty stomach or with food. The capsules should be swallowed whole at the same time each day. Taking the medication at bedtime may help reduce the incidence of nausea. Treatment with this product should be initiated within 8 weeks after the completion of platinum-based chemotherapy. If a dose is missed or if vomiting occurs after taking the medication, do not take an extra dose to make up for it; simply take the next scheduled dose at the regular time. 2. If a Grade ≥3 non-hematologic adverse reaction occurs, suspend treatment. If the adverse reaction resolves within 28 days, resume treatment at a dose of 200 mg. If a Grade ≥3 non-hematologic adverse reaction recurs at this dose, suspend treatment again. If the adverse reaction resolves within 28 days, resume treatment at a dose of 100 mg. If a Grade ≥3 non-hematologic adverse reaction recurs at this dose and does not resolve within 28 days, permanently discontinue the drug.

3. Upon the first occurrence of a platelet count of ≤1,000/μL or a hemoglobin level recovering to >9 g/dL, reduce the dose to 200 mg and resume treatment. If the aforementioned condition recurs, suspend treatment. If the neutrophil count recovers to >1,000/μL or the hemoglobin level recovers to >9 g/dL within 28 days, reduce the dose to 100 mg and resume treatment. If the neutrophil count fails to recover to >1,000/μL or the hemoglobin level fails to recover to >9 g/dL within 28 days—or if, at the 100 mg dose, the neutrophil count remains <1,000/μL or the hemoglobin level remains <8 g/dL—permanently discontinue the drug.

5. If a platelet count of ≤10,000/μL occurs, consider platelet transfusion. If the patient is concurrently taking antiplatelet agents or anticoagulants, consider discontinuing the concomitant use of these medications or administering a higher dose of platelets via transfusion.