Distribution: Niraparib is 83.0% bound to human plasma proteins. The average (±SD) apparent volume of distribution (Vd/F) was 1220 (±1114) L. In a population pharmacokinetic analysis, the Vd/F of Niraparib was 1074 L in cancer patients.
Elimination: Following multiple daily doses of 300 mg Niraparib, the mean half-life (t1/2) is 36 hours. In a population pharmacokinetic analysis, the apparent total clearance (CL/F) of niraparib was 16.2 L/h in cancer patients.
Metabolism: Niraparib is metabolized primarily by carboxylesterases (CEs) to form a major inactive metabolite, which subsequently undergoes glucuronidation.
Excretion: Following administration of a single oral 300 mg dose of radio-labeled Niraparib, the average percent recovery of the administered dose over 21 days was 47.5% (range 33.4% to 60.2%) in urine and 38.8% (range 28.3% to 47.0%) in feces. In pooled samples collected over 6 days, unchanged Niraparib accounted for 11% and 19% of the administered dose recovered in urine and feces, respectively
Dosage & Administration
Niraparib is for oral use. The capsules should be swallowed whole with water. The capsules should not be chewed or crushed. Niraparib can be taken without regard to meals.
Induction of CYPs (CYP1A2 and CYP3A4): Neither Niraparib nor M1 is a CYP3A4 inducer in vitro. In vitro, Niraparib weakly induces CYP1A2 at high concentrations and the clinical relevance of this effect would not be completely ruled out. M1 is not a CYP1A2 inducer. Therefore, caution is recommended when niraparib is combined with active substances the metabolism of which is CYP1A2-dependent and, notably, those having a narrow therapeutic range (e.g. clozapine, theophylline and ropinirole).
Pregnancy & Lactation
Pregnancy: There are no or limited amount of data from the use of Niraparib in pregnant women. Animal reproductive and developmental toxicity studies have not been conducted. However, based on its mechanism of action, niraparib could cause embryonic or foetal harm, including embryo-lethal and teratogenic effects, when administered to a pregnant woman. It should not be used during pregnancy.
Breast-feeding: It is unknown whether it or its metabolites are excreted in human milk. Breast-feeding is contraindicated during administration of it and for 1 month after receiving the last dose.
Fertility: There are no clinical data on fertility. A reversible reduction of spermatogenesis was observed in rats and dogs.
Precautions & Warnings
Hypertension including hypertensive crisis: Hypertension, including hypertensive crisis, has been reported with the use of it. Pre-existing hypertension should be adequately controlled before starting its treatment. Blood pressure should be monitored monthly for the first year and periodically thereafter during treatment with it. Hypertension should be medically managed with antihypertensive medicinal products as well as adjustment of the Niraparib dose, if necessary. In the clinical programme, blood pressure measurements were obtained on Day 1 of each 28-day cycle while the patient remained on it. In most cases, hypertension was controlled adequately using standard antihypertensive treatment with or without its dose adjustment. Niraparib should be discontinued in case of hypertensive crisis or if medically significant hypertension cannot be adequately controlled with antihypertensive therapy.
Pregnancy/contraception: Niraparib should not be used during pregnancy or in women of childbearing potential not willing to use reliable contraception during therapy and for 1 month after receiving the last dose of it. A pregnancy test should be performed on all women of childbearing potential prior to treatment.
Lactose: Niraparib hard capsules contain lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose galactose malabsorption should not take this medicine.
Tartrazine (E102): This medicinal product contains tartrazine (E 102), which may cause allergic reactions.
Use in Special Populations
Paediatric population: The safety and efficacy of niraparib in children and adolescents below 18 years of age have not yet been established. No data are available.
Renal impairment: No dose adjustment is necessary for patients with mild to moderate renal impairment. There are no data in patients with severe renal impairment or end-stage renal disease undergoing hemodialysis; use with caution in these patients.
Hepatic impairment: No dose adjustment is needed in patients with mild to moderate hepatic impairment. There are no data in patients with severe hepatic impairment; use with caution in these patients.