Nirova

FDA-Approved Indications:

• Maintenance Treatment of Ovarian Cancer: Indicated for adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.
• First-Line Maintenance in Advanced Ovarian Cancer: For adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to initial platinum-based chemotherapy, regardless of BRCA mutation status.

Clinically Accepted Off-Label Uses:

• Under investigation in other cancers such as metastatic castration-resistant prostate cancer and breast cancer (in BRCA-mutated patients) as part of ongoing clinical trials and emerging treatment strategies.

Adult Dosage:

• Initial dose: 300 mg orally once daily.
• Dose adjustments may be required based on body weight and platelet count:
• Patients <77 kg or platelet count <150,000/µL: Consider starting at 200 mg once daily.
• Administer at the same time each day, with or without food.

Dose Adjustments:

• Hematologic Toxicity: Hold dose for grade 3+ thrombocytopenia, neutropenia, or anemia. Resume at a reduced dose once resolved.
• Non-Hematologic Toxicity: Interrupt or reduce dose based on severity (e.g., fatigue, hypertension, nausea).

Special Populations:

• Renal Impairment: No dose adjustment for mild/moderate impairment; not recommended in severe impairment.
• Hepatic Impairment:
• Mild: No dose adjustment required.
• Moderate: Reduce starting dose to 200 mg once daily.
• Severe: Use not recommended.
• Elderly: No specific dose adjustment recommended but monitor closely.

Pediatric Use: Not established.

Route: Oral

Duration: Until disease progression or unacceptable toxicity.

Niraparib is a selective inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes, primarily PARP-1 and PARP-2. These enzymes play a critical role in DNA repair through the base excision repair pathway. In cancer cells with defective homologous recombination repair mechanisms (such as those with BRCA1/2 mutations), inhibition of PARP leads to accumulation of DNA damage, resulting in cell death via synthetic lethality. This mechanism is particularly effective in BRCA-mutated and homologous recombination-deficient (HRD) cancers.

• Absorption: Rapid oral absorption; peak plasma concentration (Tmax) occurs at 3-4 hours post-dose.
• Bioavailability: High oral bioavailability.
• Distribution: Widely distributed; volume of distribution ~1,220 L.
• Protein Binding: ~83% bound to plasma proteins.
• Metabolism: Primarily metabolized via carboxylesterases to inactive metabolites; minor CYP involvement.
• Half-life: Approximately 36 hours.
• Excretion: ~47.5% in urine (mainly metabolites), ~38.8% in feces.

• Pregnancy: Not assigned an FDA pregnancy category under the new labeling rule. Based on mechanism of action and animal data, Niraparib may cause fetal harm. Not recommended during pregnancy.
• Lactation: Unknown if excreted in human milk. Due to potential for serious adverse reactions in breastfed infants, women should not breastfeed during treatment and for 1 month after the final dose.

• Primary Class: Antineoplastic Agent
• Subclass: PARP (Poly ADP-Ribose Polymerase) Inhibitor
• Generation: First-generation selective PARP inhibitor

• Known hypersensitivity to Niraparib or any of its components.
• Severe uncontrolled hypertension or hypertensive crisis history (relative contraindication).
• Severe hepatic impairment.
• Pregnancy and breastfeeding (due to potential fetal/infant harm).

• Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): Reported in <1% of patients; discontinue if confirmed.
• Bone Marrow Suppression: Monitor CBC weekly for first month, then monthly.
• Hypertension/Hypertensive Crisis: Monitor blood pressure regularly; manage with antihypertensives.
• Posterior Reversible Encephalopathy Syndrome (PRES): Rare; consider in patients with seizures, headache, visual disturbances.
• Fatigue and Nausea: Very common; manage supportively.
• Secondary malignancies: Long-term risk under investigation.

Common Adverse Effects (≥10%):

• Hematologic: Thrombocytopenia, anemia, neutropenia.
• Gastrointestinal: Nausea, vomiting, constipation, decreased appetite.
• Neurological: Fatigue, headache, insomnia.
• Cardiovascular: Hypertension.
• Others: Back pain, dizziness, dysgeusia.

Serious or Rare Adverse Effects:

• Myelodysplastic syndrome (MDS) / acute myeloid leukemia (AML)
• Hypertensive crisis
• PRES
• Secondary malignancies (long-term use)

Timing & Severity:

• Most side effects occur within the first 3 months.
• Hematologic toxicities may require dose interruption or reduction.

• CYP Enzyme System: Niraparib is not a significant substrate or inhibitor of CYP450 enzymes. Low potential for CYP-mediated drug interactions.
• P-glycoprotein Substrates: Use caution when co-administered with P-gp substrates (e.g., digoxin, dabigatran).
• No Known Major Food or Alcohol Interactions: Can be taken with or without food; avoid alcohol due to additive fatigue or liver burden.

• FDA Updates: Expanded approval for use in first-line maintenance irrespective of BRCA mutation (including HRD-negative tumors).
• NCCN Guidelines: Included in maintenance therapy regimens for platinum-responsive ovarian cancer.
• Ongoing Trials: Under evaluation for additional cancers including breast, pancreatic, and prostate cancers.

• Temperature: 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).
• Humidity/Light: Protect from moisture and light.
• Handling: Keep in original container. Do not split or crush capsules.
• Special Instructions: Keep out of reach of children. Dispose of unused medication per local hazardous drug handling regulations.