Overview
11 DESCRIPTION AKEEGA ® (niraparib and abiraterone acetate) tablets contain niraparib tosylate (as the monohydrate) and abiraterone acetate. Niraparib Niraparib is a 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).
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 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 .
Indications
- 1 INDICATIONS AND USAGE AKEEGA with prednisone is indicated for the treatment of adult patients with deleterious or suspected deleterious BRCA2 -mutated ( BRCA2 m) metastatic castration-sensitive prostate cancer (mCSPC). AKEEGA with prednisone is indicated for the treatment of adult patients with deleterious or suspected deleterious BRCA -mutated ( BRCA m) metastatic castration-resistant prostate cancer (mCRPC). Select patients for therapy based on an FDA-approved test for AKEEGA [see Dosage and Administration (2.1) ] .
Common Doses
- 200 mg
- 000 mg
- 5 mg
- 10 mg
Dosage
2 DOSAGE AND ADMINISTRATION BRCA2 m mCSPC: The recommended dosage of AKEEGA is 200 mg niraparib/1,000 mg abiraterone acetate orally once daily in combination with 5 mg prednisone daily until disease progression or unacceptable toxicity. ( 2.2 ) BRCA m mCRPC : The recommended dosage of AKEEGA is 200 mg niraparib/1,000 mg abiraterone acetate orally once daily in combination with 10 mg prednisone daily until disease progression or unacceptable toxicity. ( 2.
Contraindications
- 4 CONTRAINDICATIONS None. None. ( 4 )
Side Effects
- 6 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.
Interactions
- 7 DRUG INTERACTIONS Strong CYP3A4 Inducers: Avoid coadministration. ( 7.1 ) CYP2D6 Substrates: Avoid coadministration of AKEEGA with CYP2D6 substrates for which minimal changes in concentration may lead to serious toxicities. If alternative treatments cannot be used, consider a dose reduction of the concomitant CYP2D6 substrate. ( 7.2 ) 7.1 Effect of Other Drugs on AKEEGA Effect of CYP3A4 Inducers Avoid coadministration with strong CYP3A4 inducers [see Clinical Pharmacology (12.3) ] . Abiraterone is a substrate of CYP3A4.