AKEEGA
Clinical safety rating
cautionComprehensive clinical and safety monograph for AKEEGA (AKEEGA).
Comprehensive clinical and safety monograph for AKEEGA (AKEEGA).
Treatment of adult patients with deleterious or suspected deleterious BRCA-mutated (germline and/or somatic) metastatic castration-resistant prostate cancer (mCRPC) in combination with prednisone.
Niraparib is a poly (ADP-ribose) polymerase (PARP) inhibitor that inhibits PARP-1, PARP-2, and PARP-3, leading to DNA damage repair inhibition and apoptosis in BRCA-mutated cells. Abiraterone acetate is a prodrug converted to abiraterone, a CYP17A1 inhibitor that suppresses androgen biosynthesis in testicular, adrenal, and prostate tumor tissues.
| Metabolism | Niraparib is primarily metabolized by carboxylesterases (CEs) and to a lesser extent by CYP1A2 and CYP2D6. Abiraterone acetate is hydrolyzed to abiraterone, which is then metabolized by CYP3A4 and CYP2D6. |
| Excretion | Renal: ~85% (primarily as unchanged drug); Biliary/Fecal: ~15%. |
| Half-life | Terminal half-life: 17–30 hours (mean ~24 h); allows once-daily dosing but may require dose adjustment in renal impairment. |
| Protein binding | ~99% (bound primarily to α1-acid glycoprotein and albumin). |
| Volume of Distribution | Vd: ~1.5–2.0 L/kg (indicates extensive tissue distribution). |
| Bioavailability | Oral: ~90% (high oral bioavailability). |
| Onset of Action | Oral: 2–3 hours (time to achieve steady-state plasma concentrations). |
| Duration of Action | 24 hours (supports once-daily dosing; effect persists over dosing interval based on exposure). |
| Molecular Weight | 520.6 |
Recommended dose: 240 mg (niraparib) / 500 mg (abiraterone acetate) orally once daily with or without food.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (eGFR ≥30 mL/min). Not recommended for severe renal impairment (eGFR <30 mL/min) or end-stage renal disease. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh class C). No dose adjustment for mild (Child-Pugh class A) or moderate (Child-Pugh class B) impairment; but monitor closely for toxicity. |
| Pediatric use | Safety and efficacy not established in pediatric patients; no recommended dose. |
| Geriatric use | No specific dose adjustment required. Clinical studies included patients ≥65 years; increased risk of adverse effects such as hypertension, hypokalemia, and fatigue. Monitor renal function and electrolytes regularly. |
| 1st trimester | Risk cannot be ruled out. Adequate human studies are lacking; animal studies may show risk. Use only if benefit justifies potential risk. |
| 2nd trimester | Risk cannot be ruled out. Use only if clearly needed and potential benefit outweighs risk. |
| 3rd trimester | Risk cannot be ruled out. May cause fetal harm in animal studies; avoid use in pregnant women unless absolutely necessary. |
Clinical note
Comprehensive clinical and safety monograph for AKEEGA (AKEEGA).
| Placental transfer | Based on molecular weight and pharmacokinetic properties, placental transfer is expected. In animal studies, the drug crossed the placenta and was detected in fetal tissues. |
| Breastfeeding | It is not known whether this drug is excreted in human milk. Due to potential for serious adverse reactions in nursing infants, breastfeeding is not recommended during treatment and for at least 4 months after last dose. |
| Lactation Rating | L5 |
| Teratogenic Risk | AKEEGA (niraparib and abiraterone acetate) is contraindicated in pregnancy. Based on its mechanism of action and findings in animal studies, niraparib can cause fetal harm. Abiraterone acetate is also associated with fetal risks. First trimester exposure may cause embryofetal lethality and teratogenicity. Second and third trimester exposure may impair fetal adrenal function and androgen-dependent development. |
| Fetal Monitoring | Pregnancy testing is required before initiating therapy. Females of reproductive potential should use effective contraception during treatment and for 6 months after the last dose. Monitor for signs of adrenal insufficiency, hepatotoxicity, hypertension, hypokalemia, and fluid retention in both mother and fetus. Fetal monitoring for growth and development is recommended if exposure occurs. |
| Fertility Effects | Niraparib may impair fertility in human females based on animal studies showing effects on female reproductive organs. Abiraterone acetate may impair fertility in males based on animal studies showing decreased sperm counts and motility. The reversibility of these effects is unknown. |
■ FDA Black Box Warning
AKEEGA can cause severe and persistent hypertension, hypokalemia, and fluid retention due to mineralocorticoid excess, especially in patients with renal impairment. Monitor blood pressure, serum potassium, and fluid status regularly.
| Serious Effects |
PregnancyBreastfeedingSevere hepatic impairmentHypersensitivity to active substance or any excipients
| Precautions | Hypertension, hypokalemia, and fluid retention due to mineralocorticoid excess, Adrenocortical insufficiency, Hepatotoxicity, Cardiovascular effects including QT prolongation, Bone marrow suppression (anemia, thrombocytopenia, neutropenia), Fetal harm if used during pregnancy |
| Food/Dietary | Avoid food and beverages containing grapefruit, grapefruit juice, Seville oranges, and starfruit as they inhibit CYP3A4 and may increase abiraterone exposure. Take AKEEGA on an empty stomach (no food for at least 1 hour before or 2 hours after). Avoid high-fat meals as they increase abiraterone absorption. |
| Clinical Pearls | AKEEGA (niraparib and abiraterone acetate) is indicated for BRCA-positive metastatic castration-resistant prostate cancer. Monitor for myelosuppression (CBC at baseline and monthly), hypertension (BP weekly for first month then monthly), hypokalemia, and hepatotoxicity (LFTs at baseline and monthly). CYP3A4 inhibitors increase abiraterone exposure; avoid strong inhibitors or reduce dose. Corticosteroid co-administration (prednisone 5 mg BID) is required to manage mineralocorticoid excess. Niraparib may cause fetal harm; confirm pregnancy status before initiation. |
| Patient Advice | Take tablets on an empty stomach, at least 1 hour before or 2 hours after a meal. · Swallow tablets whole; do not crush or chew. · Avoid grapefruit, grapefruit juice, Seville oranges, and starfruit during treatment. · Use effective contraception during treatment and for 4 months after the last dose for females and 3 months for males. · Report signs of bone marrow suppression: fever, bruising, bleeding, or unusual tiredness. · Report symptoms of high blood pressure: severe headache, blurred vision, or chest pain. · Take prednisone exactly as prescribed; do not stop abruptly. · Avoid pregnancy; discuss fertility preservation options before starting treatment. · Take missed doses if within 12 hours of scheduled time; otherwise skip and resume next day. · Store at room temperature; keep in original container. |
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