MEGACE ES
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MEGACE ES (MEGACE ES).
Megestrol acetate is a synthetic progestin that inhibits pituitary gonadotropin secretion, leading to suppression of ovarian and testicular hormone production. It also has antineoplastic effects possibly through local action on hormone-sensitive tissues and stimulates appetite via modulation of neuropeptide Y and other appetite-regulating factors.
| Metabolism | Metabolized primarily in the liver via cytochrome P450 (CYP3A4) to various hydroxylated metabolites. The drug undergoes conjugation and is excreted mainly in urine and feces. |
| Excretion | Primarily renal (≤1% unchanged) and biliary; extensive metabolism to inactive glucuronide conjugates excreted in feces. |
| Half-life | Approximately 34 hours in plasma; steady-state achieved after 2-3 weeks of daily dosing. |
| Protein binding | High (≥90%) bound to albumin. |
| Volume of Distribution | Not well defined in literature; estimated ~20 L based on distribution studies, indicating extensive tissue binding. |
| Bioavailability | Oral bioavailability >95%; not significantly affected by food. |
| Onset of Action | Clinical effects (appetite stimulation, weight gain) may be observed within 2-4 weeks of oral administration. |
| Duration of Action | Sustained for days after discontinuation due to long half-life; weight gain persists for weeks. |
625 mg orally once daily (MEGACE ES suspension contains 625 mg/5 mL; shake well before use). For appetite stimulation in cachexia.
| Dosage form | SUSPENSION |
| Renal impairment | No specific dose adjustment required; monitor for fluid retention in severe impairment (CrCl <30 mL/min). |
| Liver impairment | No formal Child-Pugh based guidelines; use with caution in severe hepatic impairment due to potential for increased exposure. |
| Pediatric use | Not approved for pediatric use; safety and efficacy not established. For off-label use, typical dosing is 400-800 mg/m²/day orally divided 1-2 times daily (limited data). |
| Geriatric use | No specific dose adjustment; monitor for thromboembolic events and fluid retention; consider lower starting dose due to comorbidities and polypharmacy. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MEGACE ES (MEGACE ES).
| Breastfeeding | Progestins are excreted in breast milk in low amounts (M/P ratio not established for megestrol acetate specifically). Limited data; theoretical risk of hormonal effects in infant. Use caution; discontinue or avoid breastfeeding per risk-benefit assessment. |
| Teratogenic Risk | FDA Pregnancy Category D. First trimester: Androgenic effects on female fetus, including pseudohermaphroditism (labial fusion, clitoral enlargement) and vaginal agenesis. Second trimester: Risk of genital ambiguity persists, but structural teratogenicity lower. Third trimester: Concerns about fetal growth restriction, macrosomia, and persistent neonatal genital effects. |
■ FDA Black Box Warning
Megestrol acetate is contraindicated in pregnancy. Boxed warning: Use during pregnancy is associated with an increased risk of congenital abnormalities, including genital abnormalities in male and female fetuses. Women of childbearing potential should be advised to avoid pregnancy during treatment.
| Serious Effects |
["Pregnancy","Known hypersensitivity to megestrol acetate or any component of the formulation","Use as a diagnostic test for pregnancy"]
| Precautions | ["Thromboembolic events: increased risk of deep vein thrombosis, pulmonary embolism, and myocardial infarction.","Adrenal suppression: may cause Cushing's syndrome-like effects and suppress hypothalamic-pituitary-adrenal axis.","Hyperglycemia: may induce new-onset diabetes or worsen glycemic control in diabetic patients.","Fluid retention: caution in patients with cardiovascular disease or renal impairment.","Use in HIV patients: risk of adrenal insufficiency upon abrupt discontinuation.","Impairment of fertility: may cause menstrual irregularities and testicular atrophy."] |
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| Fetal Monitoring | Monitor fetal growth (ultrasound) for macrosomia or intrauterine growth restriction. Assess fetal genitalia if exposed in first trimester (for masculinization). Monitor blood pressure and glucose due to potential for insulin resistance and hypertension. |
| Fertility Effects | May cause amenorrhea and oligo-ovulation due to progestogenic suppression of gonadotropins. Can delay fertility return; long-term use may impair ovarian function. No known permanent infertility. |