abiraterone acetate and niraparib

Action and Spectrum

Actions and Spectrum: 

abiraterone acetate is used in the treatment of advanced prostate cancer. It inhibits the enzyme CYP17A1, which produces androgens (male hormones), including testosterone. Androgens often fuel prostate cancer growth. By inhibiting CYP17A1, abiraterone acetate reduces the production of androgens, effectively depriving the cancer cells of their fuel source. 

niraparib is a PARP inhibitor used to treat certain types of ovarian cancer and other solid tumors. PARP (poly ADP-ribose polymerase) is an enzyme involved in DNA repair. Inhibiting PARP prevents cancer cells, especially those with DNA repair defects (such as BRCA mutations), from effectively repairing DNA damage. This leads to the accumulation of DNA damage and eventual cell death. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

All grades 

Lymphocytes decreased (55%) 

Musculoskeletal pain (44%) 

Fatigue (43%) 

Platelets decreased (37%) 

Alkaline phosphatase (ALP) increased (34%) 

Nausea (33%) 

Hemoglobin decreased (67%) 

White blood cell (WBC) decreased (48%) 

Fatigue (43%) 

Constipation (34%) 

Hypertension (33%) 

Grade 3 or 4 

Lymphocytes decreased (22%) 

Hypertension (14%) 

Hemoglobin decreased (26%) 

1-10% 

ALT increased (5%) 

Cerebrovascular accident (4.4%) 

Deep vein thrombosis (2.7%) 

Rash (7%) 

AST increased (5%) 

Pulmonary embolism (2.7%) 

Acute kidney injury (2.7%) 

All grades 

Arrhythmia (10%) 

Pyrexia (10%) 

Weight decreased (10%) 

Fall (10%) 

Grade 3 or 4 

Neutrophils decreased (7%) 

Fatigue (5%) 

Musculoskeletal pain (4%) 

Platelets decreased (8%) 

WBC decreased (6%) 

Potassium decreased (5%) 

Urinary tract infection (3%) 

<1% 

Grade 3 or 4 

ALT increased (0.9%) 

Potassium increased (0.9%) 

Black Box Warning

Black box warning: 

None 

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

None 

Caution: 

• Hepatotoxicity has been reported with abiraterone acetate. Safety hasn’t been established for moderate/severe hepatic impairment. Monitor serum bilirubin, AST, and ALT if hepatotoxicity symptoms arise. 
• Adrenocortical insufficiency can occur with abiraterone and prednisone, especially if steroids are interrupted, reduced, or during stress. Monitor for symptoms and consider tests to confirm the diagnosis. 
• The risk of hypoglycemia exists, mainly when used with diabetes medications. Severe hypoglycemia has occurred with thiazolidinediones or repaglinide. Monitor blood glucose and adjust antidiabetic drug dosage as needed. 
• Avoid combining niraparib/abiraterone with prednisone and Ra-223 dichloride outside clinical trials. 
• niraparib as a single agent, can lead to posterior reversible encephalopathy syndrome (PRES). Discontinue and treat if PRES is suspected. 

Pregnancy / Lactation

Pregnancy consideration: abiraterone has been linked to fetal damage and pregnancy loss.  

niraparib can potentially induce teratogenicity and embryofetal mortality since it is genotoxic and targets actively proliferating cells in animals and people. 

Lactation: Safety and efficacy not established. The excretion of the drug in human breast milk is unknown. 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 

<b>Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

abiraterone is used in the treatment of advanced prostate cancer. It works by inhibiting the enzyme CYP17A1, which plays a role in androgen biosynthesis. By blocking this enzyme, abiraterone reduces the production of androgens, fueling prostate cancer cell growth. 

niraparib is a PARP inhibitor used to treat certain types of ovarian cancer and other solid tumors. It works by inhibiting the PARP enzyme involved in DNA repair. Inhibition of PARP leads to the accumulation of DNA damage and eventual cell death, particularly in cancer cells with deficiencies in DNA repair mechanisms. 

Pharmacokinetics: 

Absorption 

In steady-state conditions, the highest concentration of niraparib in the blood is 831 ng/mL, and it reaches this peak level around 3 hours after administration. At steady-state, abiraterone acetate’s highest concentration in the bloodstream is 151 ng/mL, reached approximately 1.5 hours after administration.  

Distribution 

niraparib has a large volume of distribution, with a capacity to spread throughout the body, measured at 1,117 liters. Around 83% of niraparib binds to human plasma proteins. 

abiraterone acetate has a notably large volume of distribution, with a capacity to widely distribute throughout the body, measured at 25,774 liters. More than 99% of abiraterone acetate binds to various human plasma proteins, including albumin and alpha-1 acid glycoprotein.  

Metabolism 

niraparib is processed by carboxylesterases through metabolism. It has a relatively long elimination half-life of 62 hours, indicating how long it takes half of the drug to leave the body. abiraterone acetate undergoes rapid conversion into abiraterone in the body, and its metabolism involves enzymes CYP3A4 and SULT2A1.  

Elimination and Excretion 

The clearance rate of niraparib is 16.7 L/hr, showing how quickly the drug is removed from the blood. niraparib is eliminated through urine (48%, 11% of it unchanged) and feces (39%, 19%). The drug’s elimination half-life is 20 hours, indicating its duration in the body before being cleared. 

The clearance rate of abiraterone acetate is 1673 L/hr, indicating its efficient removal from the bloodstream. abiraterone acetate is primarily eliminated through feces (88%), with a smaller portion excreted in urine (5%). 

Adminstartion

Administration: 

Oral administration 

Take on a full stomach.  

Do not consume anything for 2 hours before and 1 hour after administration.  

Do not crush, chew, or break pills; swallow them whole with water. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: abiraterone acetate and niraparib 

Why do we use abiraterone acetate and niraparib? 

niraparib and abiraterone are used for the treatment of: 

• Ovarian Cancer: It’s used as maintenance therapy for adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy. 
• Advanced Ovarian, Fallopian Tube, or Primary Peritoneal Cancer: It’s a treatment for patients who have received three or more prior chemotherapy regimens. 
• Prostate Cancer: It’s indicated for metastatic castration-resistant prostate cancer (mCRPC). 
• Metastatic High-Risk Castration-Sensitive Prostate Cancer: It’s combined with prednisone or prednisolone.