AKEEGA (niraparib tosylate/abiraterone acetate)

There are 2 contraindications. Absolute contraindication.

Contraindication List
Child-pugh class B hepatic impairment
Child-pugh class C hepatic impairment

There are 6 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Anemia
Disease of liver
Hypokalemia
Neutropenic disorder
Pregnancy
Thrombocytopenic disorder

There are 4 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Acute myocardial infarction
Cardiac arrhythmia
Chronic heart failure
Hypertension

There are 39 severe adverse reactions.

More Frequent	Less Frequent
Abnormal hepatic function tests Accidental fall Anemia Cardiac arrhythmia Fracture Hypertension Hypokalemia Hypomagnesemia Increased alanine transaminase Increased aspartate transaminase Leukopenia Lymphopenia Neutropenic disorder Thrombocytopenic disorder	Atrial fibrillation Hyperbilirubinemia Hypokalemia Increased alanine transaminase Increased aspartate transaminase Kidney disease with reduction in glomerular filtration rate (GFr)

Rare/Very Rare
Acute hepatic failure Acute myeloid leukemia Acute myocardial infarction Adrenocortical insufficiency Anaphylaxis Cardiomegaly Cardiomyopathy Heart failure Hepatitis Hypersensitivity drug reaction Hypertensive crisis Hypoglycemic disorder Interstitial pneumonitis Myelodysplastic syndrome Myocardial ischemia Pancytopenia Posterior reversible encephalopathy syndrome Renal failure Rhabdomyolysis

There are 53 less severe adverse reactions.

More Frequent

Less Frequent

Abdominal distension Acute abdominal pain Anorexia Arthralgia Back pain Body fluid retention Bruising Constipation Cough Diarrhea Dizziness Dysgeusia Dyspepsia Dyspnea Edema Fatigue Fever Flushing General weakness Headache disorder Hematuria Hypercholesterolemia Hyperglycemia Hypertriglyceridemia Increased urinary frequency Insomnia Musculoskeletal pain Myalgia Nausea Nocturia Palpitations Pharyngitis Skin rash Stomatitis Symptoms of anxiety Upper respiratory infection Urinary tract infection Vomiting Xerostomia

Bronchitis Chest pain Conjunctivitis Depression Epistaxis Increased pulse rate Peripheral edema Tachycardia Weight loss

Rare/Very Rare
Acute cognitive impairment Hallucinations Memory impairment Myopathy Skin photosensitivity

The safety and efficacy of niraparib/abiraterone have not been established in females. There are no human data on the use of niraparib/abiraterone in pregnant women. Based on findings from animal studies and the mechanism of action, niraparib/abiraterone can cause fetal harm and potential loss of 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 (e.g., bone marrow). In animal reproduction studies, oral administration of abiraterone acetate to pregnant rats during organogenesis (gestational days 6-17) caused adverse developmental effects at maternal exposures approximately >=0.03 times the human exposure (AUC) at the recommended dose.

Findings included embryo-fetal lethality (increased postimplantation loss and resorptions and decreased number of live fetuses), fetal developmental delay, and urogenital effects (bilateral ureter dilation) at dosages >=10 mg/kg/day, decreased fetal anogenital distance at >=30 mg/kg/day, and decreased fetal body weight at 100 mg/kg/day, which represents approximately 0.03, 0.1, and 0.3 times the AUC of patients receiving 1,000 mg of abiraterone acetate, respectively.

The safety and efficacy of niraparib/abiraterone have not been established in females. There is no information available on the presence of niraparib or abiraterone in human milk, or on the effects of these drugson the breast-fed child or milk production.

Of the 113 patients with BRCAgene alteration(s) who received niraparib/abiraterone in the MAGNITUDE trial, 34.5% of patients were less than 65 years of age, 38.9% of patients were 65 to 74 years, and 26.5%

were 75 years and older. There was an insufficient number of patients withBRCA gene alteration(s) treated with niraparib/abiraterone in the MAGNITUDE trial to accurately characterize efficacy or safety by age.