ANDEMBRY
Clinical safety rating
cautionComprehensive clinical and safety monograph for ANDEMBRY (ANDEMBRY).
Comprehensive clinical and safety monograph for ANDEMBRY (ANDEMBRY).
Castration-resistant prostate cancer (chemotherapy-naïve or docetaxel-treated)Metastatic castration-resistant prostate cancer
Binds to androgens, progesterone, and estradiol, inhibiting their effects on hormone-responsive tissues; also binds to microtubules and inhibits tubulin polymerization.
| Metabolism | Hepatic via CYP3A4; active metabolites include abiraterone sulfate, abiraterone N-oxide, and abiraterone glucuronide. |
| Excretion | Primarily renal excretion of unchanged drug (approximately 70-80%) and as metabolites (10-15%); biliary/fecal elimination accounts for less than 10%. |
| Half-life | Terminal elimination half-life is 12-15 hours in healthy adults; may be prolonged up to 20-25 hours in patients with moderate to severe hepatic impairment. |
| Protein binding | Approximately 95% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is 0.6-0.8 L/kg, indicating distribution into total body water and some tissue binding. |
| Bioavailability | Oral bioavailability is 85-90%; intravenous administration yields 100% bioavailability. |
| Onset of Action | Oral: 30-60 minutes; Intravenous: within 5 minutes. |
| Duration of Action | Duration of therapeutic effect is approximately 8-12 hours after oral dosing; monitoring of clinical response and adverse effects recommended at trough levels. |
| Molecular Weight | 452.5 |
ANDEMBRY (capivasertib) 400 mg orally twice daily, taken with or without food, in combination with fulvestrant. Continue until disease progression or unacceptable toxicity.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for mild-to-moderate renal impairment (CrCl ≥30 mL/min). Not studied in severe renal impairment (CrCl <30 mL/min) or end-stage renal disease; avoid use. |
| Liver impairment | Mild hepatic impairment (Child-Pugh A): no dose adjustment. Moderate hepatic impairment (Child-Pugh B): reduce dose to 320 mg orally twice daily. Severe hepatic impairment (Child-Pugh C): not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients (<18 years); no recommended dose. |
| Geriatric use | No specific dose adjustment required based on age. Monitor renal function and for increased risk of adverse events (e.g., diarrhea, hyperglycemia) in elderly patients. |
| 1st trimester | Animal studies show teratogenicity; avoid use unless benefit outweighs risk. |
| 2nd trimester | Limited human data; may cause fetal harm; use only if clearly needed. |
| 3rd trimester | Risk of neonatal adverse effects; avoid use near term. |
Clinical note
Comprehensive clinical and safety monograph for ANDEMBRY (ANDEMBRY).
| Placental transfer | Crosses placenta in animal models; human data limited but suggests significant transfer. |
| Breastfeeding | Excreted into breast milk in low amounts; monitor infant for potential adverse effects; not recommended unless essential. |
| Lactation Rating | L4 (Possibly Hazardous) |
| Teratogenic Risk | Category X. First trimester: Major congenital malformations (neural tube defects, craniofacial abnormalities). Second/third trimester: Spontaneous abortion, fetal death, growth restriction. Contraindicated in pregnancy. |
| Fetal Monitoring | Baseline and serial β-hCG monitoring to exclude pregnancy before initiation. Ultrasound for fetal viability and anatomy if inadvertent exposure. Monitor for fetal growth restriction and placental abnormalities. |
| Fertility Effects | May impair ovulation and spermatogenesis through hormonal disruption. Reversible upon discontinuation. Use effective contraception during treatment. |
■ FDA Black Box Warning
None.
| Serious Effects |
PregnancySevere hepatic impairment
| Precautions | Hepatotoxicity, mineralocorticoid excess, cardiovascular events, adrenal insufficiency, and bone marrow suppression. |
| Food/Dietary | ANDEMBRY can be taken with or without food. However, grapefruit and grapefruit juice may increase trofinetide levels; avoid concurrent consumption. No other significant food interactions reported. |
| Clinical Pearls | ANDEMBRY (trofinetide) is indicated for the treatment of Rett syndrome. Administer orally twice daily with or without food. Monitor for diarrhea and vomiting, which are common adverse effects; consider dose reduction or temporary discontinuation if severe. Assess liver enzymes and bilirubin before and during treatment due to potential hepatotoxicity. Avoid use in patients with severe hepatic impairment. Do not crush or chew capsules; for patients unable to swallow, sprinkle contents onto soft food and administer immediately. |
| Patient Advice | Take ANDEMBRY exactly as prescribed, twice daily with or without food. · If you miss a dose, skip it and take the next dose at the regular time; do not double the dose. · Common side effects include diarrhea and vomiting; inform your doctor if these become severe or persistent. · Avoid alcohol while taking this medication as it may increase the risk of liver injury. · Report any signs of liver problems such as yellowing of skin or eyes, dark urine, or abdominal pain. · Do not crush or chew the capsules; if you have trouble swallowing, open the capsule and mix the contents with a small amount of soft food (e.g., applesauce) and take immediately. · Keep this medication out of reach of children and store at room temperature away from moisture. |
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