Niraparib Tosylate (2 brand names, 2 dosage forms, 1 route)
Available dosage forms: CAPSULE, TABLET.
Routes of administration: ORAL.
Brand Names
- AKEEGA
- ZEJULA
Indications and Usage
AKEEGA with prednisone is indicated for the treatment of adult patients with deleterious or suspected deleterious BRCA2-mutated ( BRCA2m) metastatic castration-sensitive prostate cancer (mCSPC). AKEEGA with prednisone is indicated for the treatment of adult patients with deleterious or suspected deleterious BRCA-mutated ( BRCAm) metastatic castration-resistant prostate cancer (mCRPC). Select patients for therapy based on an FDA-approved test for AKEEGA [see Dosage and Administration (2.1)] .
Contraindications
None.
Adverse Reactions
The following adverse reactions are discussed elsewhere in the labeling: Myelodysplastic syndrome/acute myeloid leukemia [see Warnings and Precautions (5.1)] Myelosuppression [see Warnings and Precautions (5.2)] Hypokalemia, fluid retention, and cardiovascular adverse reactions [see Warnings and Precautions (5.3)] Hepatotoxicity [see Warnings and Precautions (5.4)] Adrenocortical insufficiency [see Warnings and Precautions (5.5)] Hypoglycemia [see Warnings and Precautions (5.6)] Increased fractures and mortality in combination with Radium 223 Dichloride [see Warnings and Precautions (5.7)] Posterior reversible encephalopathy syndrome [see Warnings and Precautions (5.8)]
Mechanism of Action
Niraparib is an inhibitor of PARP enzymes, including PARP-1 and PARP-2, that play a role in DNA repair. In vitro studies have shown that 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. Increased niraparib‑induced cytotoxicity was observed in tumor cell lines with or without deficiencies in BRCA1/2. Niraparib decreased tumor growth in mouse xenograft models of human cancer cell lines with deficiencies in BRCA1/2 and in human patient‑derived xenograft tumor models with homologous recombination deficiency (HRD) that had either mutated or wild-type BRCA1/2. Abiraterone acetate is converted in vivo to abiraterone, an androgen biosynthesis inhibitor, that inhibits 17 α-hydroxylase/C17,20-lyase (CYP17). This enzyme is expressed in testicular, adrenal, and prostatic tumor tissues and is required for androgen biosynthesis. CYP17 catalyzes two sequential reactions: 1) the conversion of pregnenolone and progesterone to their 17α-hydroxy derivatives by 17α-hydroxylase activity and 2) the subsequent formation of dehydroepiandrosterone (DHEA) and androstenedione, respectively, by C17, 20 lyase activity. DHEA and androstenedione are androgens and are precursors of testosterone. Inhibition of CYP17 by abiraterone can also result in increased mineralocorticoid production by the adrenals [see Warnings and Precautions (5.9)] . Androgen sensitive prostatic carcinoma responds to treatment that decreases androgen levels. Androgen deprivation therapies, such as treatment with GnRH agonists or orchiectomy, decrease androgen production in the testes but do not affect androgen production by the adrenals or in the tumor. Abiraterone decreased serum testosterone and other androgens in patients in the placebo-controlled clinical trial. It is not necessary to monitor the effect of abiraterone on serum testosterone levels. Changes in serum prostate specific antigen (P
Overdosage
In the event of an overdose, administration of AKEEGA should be stopped and general supportive measures undertaken, including monitoring for arrhythmias and cardiac failure and assessing liver function. There is no specific treatment in the event of AKEEGA overdose.