Akeega Niraparib Tosylate and Abiraterone Acetate Tablets

1. Indications and Usage
Metastatic Castration-Resistant Prostate Cancer (mCRPC):
Indicated for the treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC) who have germ-line and/or somatic BRCA gene mutations.
Combination Therapy:
This indication is approved in combination with prednisone or prednisolone and androgen deprivation therapy (ADT).
2. Dosage and Administration
Recommended Dosage:
Standard Dose: 200 mg Niraparib + 1000 mg Abiraterone Acetate administered orally once daily.
Concomitant Medication: Must be taken with 10 mg of Prednisone or Prednisolone once daily.
ADT: Patients must continue ADT (e.g., GnRH analogues or bilateral orchiectomy).
Administration Instructions:
Fasting: Must be taken on an empty stomach. No food for at least 2 hours before and at least 1 hour after taking the tablet.
Swallow tablets whole with water.
3. Mechanism of Action
Dual Inhibition Strategy:
Niraparib (PARP Inhibitor): Inhibits PARP-1 and PARP-2 enzymes, preventing the repair of single-strand DNA breaks. In cells with BRCA mutations (homologous recombination deficiency), this leads to double-strand breaks and cell death (synthetic lethality).
Abiraterone Acetate (Androgen Biosynthesis Inhibitor): Inhibits CYP17A1 (17α-hydroxylase/C17,20-lyase), an enzyme essential for androgen synthesis in the testes, adrenal glands, and prostate tumor tissue.
4. Safety and Warnings
Hematologic Toxicity:
Niraparib can cause severe and life-threatening hematologic toxicities, including thrombocytopenia, anemia, and neutropenia. Regular monitoring of blood counts is required.
MDS/AML:
Development of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) has been observed in patients treated with PARP inhibitors.
Hepatotoxicity:
Liver toxicity (elevated ALT/AST or bilirubin) may occur. Monitor liver function tests periodically.
Hypertension:
Niraparib may cause hypertension. Patients should have blood pressure well-controlled before starting treatment.
Contraindications:
Contraindicated in patients with moderate or severe hepatic impairment (Child-Pugh B or C).
5. Adverse Reactions
Most Common:
Fatigue, nausea, thrombocytopenia, anemia, vomiting, constipation, abdominal pain, hypertension, and decreased appetite.
6. Drug Interactions
CYP3A Inducers:
Avoid co-administration with strong CYP3A inducers (e.g., rifampin), as they may significantly decrease abiraterone exposure.
CYP2D6 Substrates:
Abiraterone is a CYP2D6 inhibitor. Use caution when co-administering with CYP2D6 substrates.
7. Pharmaceutical Information
Chemical Description:
A fixed-dose combination tablet containing Niraparib Tosylate and Abiraterone Acetate.
Storage:
Store at room temperature (controlled room temperature 20°C to 25°C). Protect from moisture.