nically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
8.2 Lactation
Risk Summary
No data are available regarding the presence of niraparib or its metabolites in human milk, or on its effects on the breastfed infant or milk production. Because of the potential for serious adverse reactions in breastfed infants from ZEJULA, advise a lactating woman not to breastfeed during treatment with ZEJULA and for 1 month after receiving the final dose.
8.3 Females and Males of Reproductive Potential
Pregnancy Testing
ZEJULA can cause fetal harm when administered to a pregnant woman [see USE IN SPECIFIC POPULATIONS (8.1)].
A pregnancy test is recommended for females of reproductive potential prior to initiating ZEJULA treatment.
Contraception
Females
ZEJULA can cause fetal harm when administered to a pregnant woman [see USE IN SPECIFIC POPULATIONS (8.1)].
Advise females of reproductive potential to use effective contraception treatment with ZEJULA and for at least for 6 months following the last dose.
Infertility
Males
Based on animal studies, ZEJULA may impair fertility in males of reproductive potential [see NONCLINICAL TOXICOLOGY (13.1)].
8.4 Pediatric Use
Safety and effectiveness of ZEJULA have not been established in pediatric patients.
8.5 Geriatric Use
In Trial 1 (NOVA), 35% of patients were aged ≥65 years and 8% were aged ≥75 years. No overall differences in safety and effectiveness of ZEJULA were observed between these patients and younger patients but greater sensitivity of some older individuals cannot be ruled out.
8.6 Renal Impairment
No dose adjustment is necessary for patients with mild (CLcr:60 to 89 mL/min) to moderate (CLcr:30 to 59 mL/min) renal impairment. The degree of renal impairment was determined by creatinine clearance as estimated by the Cockcroft-Gault equation. The safety of ZEJULA in patients with severe renal impairment or end stage renal disease undergoing hemodialysis is unknown.
8.7 Hepatic Impairment
No dose adjustment is needed in patients with mild hepatic impairment according to the National Cancer Institute – Organ Dysfunction Working Group (NCI-ODWG) criteria. The safety of ZEJULA in patients with moderate to severe hepatic impairment is unknown.
10 OVERDOSAGE
There is no specific treatment in the event of ZEJULA overdose, and symptoms of overdose are not established. In the event of an overdose, healthcare practitioners should follow general supportive measures and should treat symptomatically.
11 DESCRIPTION
Niraparib is an orally available poly(ADP-ribose) polymerase (PARP) inhibitor.
The chemical name for niraparib tosylate monohydrate is 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole 7-carboxamide 4-methylbenzenesulfonate hydrate (1:1:1). The molecular formula is C26H30N4O5S and it has a molecular weight of 510.61 amu. The molecular structure is shown below:
Chemical Structure
Niraparib tosylate monohydrate is a white to off-white, non-hygroscopic crystalline solid. Niraparib solubility is pH independent below the pKa of 9.95, with an aqueous free base solubility of 0.7 mg/mL to 1.1 mg/mL across the physiological pH range.
Each ZEJULA capsule contains 159.4 mg niraparib tosylate monohydrate equivalent to 100 mg niraparib free base as the active ingredient. The inactive ingredients in the capsule fill are magnesium stearate and lactose monohydrate. The capsule shell consists of titanium di |
