ZEJULA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZEJULA (ZEJULA).
Poly (ADP-ribose) polymerase (PARP) enzyme inhibitor, including PARP1, PARP2, and PARP3. Inhibits PARP catalytic activity and traps PARP-DNA complexes, leading to accumulation of DNA damage and apoptosis in BRCA-deficient tumor cells.
| Metabolism | Primarily metabolized by carboxylesterases (CES1 and CES2) to yield M1 and M2 metabolites; undergoes further glucuronidation via UGT1A1 and UGT1A3. Niraparib inhibits BCRP and P-glycoprotein (P-gp) transporters. Minimal CYP-mediated metabolism. |
| Excretion | Renal: 70.9% (11.1% unchanged); fecal: 15.5%; metabolism via carboxylesterases (CES1/CES2) and renal excretion of metabolites. |
| Half-life | 36 ± 13 hours; supports twice-daily dosing; in moderate hepatic impairment (Child-Pugh B), t1/2 prolonged to 58 hours. |
| Protein binding | 83% bound to human plasma proteins (mainly albumin and α1-acid glycoprotein). |
| Volume of Distribution | 74.7 L (approx. 1.06 L/kg for 70 kg); indicates extensive tissue distribution. |
| Bioavailability | 73% following oral administration (capsule, fed or fasted). |
| Onset of Action | PRAP inhibition observed within 1 hour; clinical response (tumor shrinkage) typically within 8–12 weeks of continuous dosing. |
| Duration of Action | PARP inhibition persists for 24–48 hours post-dose; clinical duration sustained with continuous BID dosing; no accumulation beyond steady state by day 21. |
300 mg orally once daily with or without food.
| Dosage form | CAPSULE |
| Renal impairment | For GFR ≥30 mL/min, no adjustment; for GFR <30 mL/min, not recommended. |
| Liver impairment | Child-Pugh A: 300 mg once daily; Child-Pugh B: 200 mg once daily; Child-Pugh C: not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment recommended; consider age-related renal function decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ZEJULA (ZEJULA).
| Breastfeeding | No data available on niraparib presence in human milk, effects on breastfed infants, or milk production. Due to potential for serious adverse reactions in nursing infants from this antineoplastic agent, breastfeeding is contraindicated during therapy and for 1 month after the last dose. M/P ratio unknown. |
| Teratogenic Risk | ZEJULA (niraparib) is embryotoxic and teratogenic in animal studies. Based on its mechanism of action (PARP inhibition), it can cause fetal harm when administered to a pregnant woman. First trimester exposure carries highest risk for major congenital malformations. Second and third trimester exposure may lead to fetal growth restriction and oligohydramnios. There are no adequate human data; however, animal studies demonstrate embryofetal toxicity at exposures below human therapeutic levels. |
■ FDA Black Box Warning
None
| Serious Effects |
["History of hypersensitivity to niraparib or any excipients"]
| Precautions | ["Bone marrow suppression (anemia, neutropenia, thrombocytopenia): Monitor blood counts at baseline and monthly","Myelodysplastic syndrome/acute myeloid leukemia (MDS/AML): Reported in patients treated with PARP inhibitors","Cardiovascular effects: Hypertension and hypertensive crisis; monitor blood pressure monthly","Embryo-fetal toxicity: Can cause fetal harm; advise contraception","Posterior reversible encephalopathy syndrome (PRES): Discontinue if PRES occurs","Hepatotoxicity: Monitor liver function tests"] |
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| Fetal Monitoring | Monitor complete blood count (CBC) every weekly for first month, then monthly for 11 months. Monitor blood pressure and heart rate monthly for first year; cardiac monitoring (ECG) if symptomatic. For pregnant patients if exposure occurs, serial fetal ultrasounds for growth and anatomy, amniotic fluid volume assessment, and non-stress test or biophysical profile in third trimester. Monitor maternal blood pressure and renal function. |
| Fertility Effects | Niraparib may impair fertility in humans. In animal studies, niraparib caused reduced fertility, ovarian atrophy, and altered estrous cycles at exposures below human therapeutic levels. In premenopausal women, amenorrhea may occur; ovarian function may not fully recover. Advise fertility preservation counseling before treatment. |