Niraparib is used as maintenance therapy for adult patients with recurrent epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer who have achieved a complete or partial response after platinum-based chemotherapy.

Niraparib is a poly (ADP-ribose) polymerase (PARP) inhibitor that targets PARP-1 and PARP-2 enzymes involved in DNA repair. Laboratory studies suggest that niraparib causes cancer cell death by blocking PARP enzyme activity and increasing the formation of PARP-DNA complexes, which leads to DNA damage, apoptosis, and cell death. Enhanced cytotoxic effects were seen in tumor cell lines regardless of whether BRCA1/2 deficiency was present. In mouse xenograft models, niraparib reduced tumor growth in cancers with BRCA1/2 deficiency as well as in tumors with homologous recombination deficiency, whether BRCA1/2 was mutated or wild type.

Absorption: The absolute bioavailability of niraparib is approximately 73%. After oral administration, peak plasma concentration (Cmax) is reached within 3 hours. Taking niraparib with a high-fat meal does not significantly affect its pharmacokinetics.

Distribution: Niraparib is 83% bound to human plasma proteins. The average apparent volume of distribution (Vd/F) is 1220 L, while population pharmacokinetic analysis in cancer patients showed a Vd/F of 1074 L.

Elimination: After multiple daily doses of 300 mg, the mean half-life of niraparib is 36 hours. In cancer patients, the apparent total clearance (CL/F) was found to be 16.2 L/h.

Metabolism: Niraparib is mainly metabolized by carboxylesterases to form a major inactive metabolite, which is then glucuronidated.

Excretion: Following a single oral 300 mg dose of radiolabeled niraparib, the average recovery over 21 days was 47.5% in urine and 38.8% in feces. Over 6 days, unchanged niraparib represented 11% of the recovered dose in urine and 19% in feces.

The recommended dose of Niraparib as monotherapy is 300 mg (three 100 mg capsules) taken orally once daily. Instruct patients to take their dose of Niraparib at approximately the same time each day. Each capsule should be swallowed whole. Niraparib may be taken with or without food. Bedtime administration may be a potential method for managing nausea. Patients should start treatment with Niraparib no later than 8 weeks after their most recent platinum-containing regimen. Niraparib treatment should be continued until disease progression or unacceptable toxicity. In the case of a missed dose of Niraparib, instruct patients to take their next dose at its regularly scheduled time. If a patient vomits or misses a dose of Niraparib, an additional dose should not be taken.

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.

Inhibition of CYPs (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4): Niraparib and its metabolite M1 do not inhibit the major CYP enzymes responsible for drug metabolism, including CYP1A1/2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4/5. Although significant inhibition of hepatic CYP3A4 is not expected, the potential for intestinal CYP3A4 inhibition at clinically relevant Niraparib concentrations has not been fully established. Therefore, caution is advised when Niraparib is coadministered with drugs that are metabolized by CYP3A4, particularly those with a narrow therapeutic index (e.g., ciclosporin, tacrolimus, alfentanil, ergotamine, pimozide, quetiapine, and halofantrine).

Induction of CYPs (CYP1A2 and CYP3A4): Niraparib and M1 are not CYP3A4 inducers in vitro. However, Niraparib may weakly induce CYP1A2 at high concentrations, and the clinical relevance of this effect cannot be entirely excluded. M1 does not induce CYP1A2. Therefore, caution is recommended when Niraparib is used with drugs metabolized by CYP1A2, especially those with a narrow therapeutic range (e.g., clozapine, theophylline, and ropinirole).

Niraparib is contraindicated in patients with hypersensitivity to the active ingredient or any of the excipients. It is also contraindicated during breast-feeding.

Common adverse effects reported with Niraparib monotherapy include nausea, thrombocytopenia, fatigue or asthenia, anaemia, constipation, vomiting, abdominal pain, neutropenia, insomnia, headache, decreased appetite, nasopharyngitis, diarrhoea, dyspnea, hypertension, dyspepsia, back pain, dizziness, cough, urinary tract infection, arthralgia, palpitations, and dysgeusia. The most common serious adverse reactions were thrombocytopenia and anaemia.

Myelodysplastic syndrome/acute myeloid leukaemia: Myelodysplastic syndrome/acute myeloid leukaemia (MDS/AML), including fatal cases, has been reported in a small number of patients treated with Niraparib or placebo. In the pivotal Phase 3 ENGOT-OV16 trial, the incidence of MDS/AML in patients receiving Niraparib (1.4%) was comparable to those receiving placebo (1.1%). Overall, MDS/AML occurred in 7 out of 751 (0.9%) patients treated with Niraparib in clinical studies.The time to onset of MDS/AML ranged from 1 month to more than 2 years after starting Niraparib. These cases were typical of secondary, therapy-related MDS/AML. All affected patients had received multiple platinum-based chemotherapy regimens, and many had also been exposed to other DNA-damaging agents and radiotherapy. Some patients had a prior history of bone marrow dysplasia. If MDS and/or AML is confirmed during Niraparib treatment, therapy should be discontinued and appropriate management initiated.

Hypertension, including hypertensive crisis: Hypertension, including hypertensive crisis, has been reported with Niraparib use. Pre-existing hypertension should be adequately controlled before initiating therapy. Blood pressure should be monitored monthly for the first year and periodically thereafter. Hypertension should be managed with antihypertensive medications and, if necessary, adjustment of the Niraparib dose. In clinical studies, blood pressure was assessed on Day 1 of each 28-day cycle during treatment. In most cases, hypertension was effectively controlled with standard treatment, with or without dose adjustment. Niraparib should be discontinued if a hypertensive crisis occurs or if severe hypertension cannot be adequately controlled.

Pregnancy/contraception: Niraparib should not be used during pregnancy or in women of childbearing potential who are not willing to use effective contraception during treatment and for at least 1 month after the last dose. A pregnancy test should be conducted in all women of childbearing potential prior to initiating therapy.

Lactose: Niraparib hard capsules contain lactose monohydrate. Patients with rare hereditary conditions such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medication.

Tartrazine (E102): This medicinal product contains tartrazine (E102), which may cause allergic reactions.

Niraparib may rarely cause myelodysplastic syndrome or acute myeloid leukaemia, including fatal cases. If MDS or AML is confirmed, treatment should be discontinued. Hypertension, including hypertensive crisis, has also been reported. Blood pressure should be controlled before starting therapy and monitored regularly during treatment. Dose adjustment or discontinuation may be necessary if blood pressure cannot be adequately controlled. Niraparib should not be used in pregnancy or in women unwilling to use effective contraception. The capsules contain lactose monohydrate, so patients with rare hereditary galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption should avoid it. It also contains tartrazine (E102), which may cause allergic reactions.

Elderly: No dose adjustment is required for elderly patients (>65 years). However, clinical data in patients aged 75 years or older are limited.

Paediatric population: The safety and efficacy of niraparib in children and adolescents under 18 years of age have not been established. No data are available.

Renal impairment: No dose adjustment is required in patients with mild to moderate renal impairment. There are no data in patients with severe renal impairment or end-stage renal disease undergoing hemodialysis; therefore, use with caution in these patients.

Hepatic impairment: No dose adjustment is required in patients with mild to moderate hepatic impairment. There are no data in patients with severe hepatic impairment; therefore, use with caution in these patients.

There is no specific antidote for Niraparib overdose, and overdose symptoms are not clearly established. In case of overdose, general supportive care and symptomatic treatment should be given.

Cytotoxic Chemotherapy.

Store in a cool, dry place below 30°C. Do not use Niraparib if it may have been exposed to temperatures above 40°C or 104°F. Keep out of the reach and sight of children.