Niraparib

Indications

Niraparib is used for: Ovarian Cancer

Adult Dose

Ovarian Cancer Indicated for the maintenance treatment of adults with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy 300 mg PO qDay; continue until disease progression or unacceptable toxicity Hepatic impairment Mild: No dose adjustment required Moderate or severe: Not studied

Child Dose

Renal Dose

Renal impairment Mild-to-moderate (CrCl ?30 mL/min): No dose adjustment required Severe or ESRD: Not studied

Administration

May take with or without food Initiate niraparib no later than 8 weeks after their most recent platinum-containing regimen Instruct patient to take dose at about the same time each day

Contra Indications

Precautions

Myelodysplastic syndrome/acute myeloid leukemia (MDS/AML), including cases with fatal outcome, reported; discontinue drug if MDS/AML is confirmed May cause bone marrow suppression resulting in hematologic toxicities (eg, thrombocytopenia, anemia, neutropenia); do not initiate until patients have recovered from hematological toxicities caused by previous chemotherapy (grade ≤1); monitor complete blood cell counts weekly for the first month, monthly for the next 11 months of treatment, and periodically after this time (also see Dosage Modifications) Hypertension and hypertensive crisis reported; monitor BP and HR monthly for the first year and periodically thereafter during treatment; medically manage hypertension with antihypertensive medications and niraparib dose adjustment Based on its mechanism of action, can cause fetal harm if administered to a pregnant woman

Pregnancy-Lactation

Pregnancy Niraparib has the potential to cause teratogenicity and/or embryo-fetal death since niraparib is genotoxic and targets actively dividing cells in animals and patients (eg, bone marrow) A pregnancy test is recommended for females of reproductive potential prior to initiating drug Based on animal studies, may impair fertility in males of reproductive potential Contraception Advise females of reproductive potential to use effective contraception during treatment for at least 6 months following the last dose Lactation Because of the potential for serious adverse reactions in breastfed infants, advise a lactating woman not to breastfeed during treatment and for 1 month after receiving the final dose

Interactions

Adverse Effects

Side effects of Niraparib : >10% Nausea (74%) Thrombocytopenia (61%) Fatigue/asthenia (57%) Anemia (50%) Constipation (40%) Vomiting (34%) Abdominal pain/distention (33%) Neutropenia (30%) Thrombocytopenia, grades 3 or 4 (29%) Insomnia (27%) Headache (26%) Anemia, grades 3 or 4 (25%) Nasopharyngitis (23%) Rash (21%) Hypertension (20%) Neutropenia, grades 3 or 4 (20%) Mucositis/stomatitis (20%) Diarrhea (20%) Dyspepsia (20%) Myalgia (19%) Back pain (18%) Dyspepsia (18%) Dizziness (18%) Leukopenia (17%) Cough (16%) UTI (13%) Arthralgia (13%) Anxiety (11%) 1-10% Palpitations (10%) Dry mouth (10%) AST/ALT elevation (10%) Dysgeusia (10%) Hypertension, grade 3 or 4 (9%) Leukopenia, grades 3 or 4 (5%)

Mechanism of Action

Poly (ADP-ribose) polymerase (PARP) inhibitor; niraparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complexes, resulting in DNA damage, apoptosis, and cell death