MEGACE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MEGACE (MEGACE).
Megestrol acetate is a synthetic progestin that inhibits pituitary gonadotropin secretion, leading to suppression of ovarian function and reduction of sex hormone levels. It also has antineoplastic effects through interference with estrogen receptor binding and may stimulate appetite via effects on neuropeptide Y and cytokines.
| Metabolism | Primarily hepatic metabolism via reduction, hydroxylation, and conjugation; major metabolites include megestrol acetate glucuronide and other reduced derivatives. |
| Excretion | Primarily renal: ~75% as glucuronide conjugates and unchanged drug; biliary/fecal: ~25% as metabolites. |
| Half-life | Terminal elimination half-life: 70-95 hours (mean 85 hours) in chronic dosing; shorter in initial doses; clinical context: requires 3-4 weeks to reach steady state. |
| Protein binding | 90-95% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Apparent Vd: 2.5-5 L/kg; indicates extensive tissue distribution and accumulation in adipose tissue. |
| Bioavailability | Oral: 85-95% (well absorbed); absorption unaffected by food. |
| Onset of Action | Oral: Clinical effect on appetite/weight gain within 2-4 weeks; measurable effect on cachexia may take 6-8 weeks. |
| Duration of Action | Duration of appetite stimulation persists for 2-3 months after discontinuation; weight gain may be maintained for 4-6 weeks post-therapy. |
Oral: 625 mg (suspension) or 400–800 mg (tablets) once daily.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for renal impairment. |
| Liver impairment | No specific Child-Pugh based adjustment; use caution in severe hepatic impairment. |
| Pediatric use | Weight-based dosing: 7.5–15 mg/kg/day orally in 1–2 divided doses; max 800 mg/day. |
| Geriatric use | Start at lowest recommended adult dose; monitor for fluid retention and thromboembolic events. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MEGACE (MEGACE).
| Breastfeeding | Excretion into human milk is unknown; M/P ratio not determined. Due to potential for adverse effects in the nursing infant (hormonal effects), manufacturer recommends discontinuing nursing or drug, considering importance of drug to mother. |
| Teratogenic Risk | First trimester: FDA pregnancy category D. Based on animal studies and human data, megestrol acetate (MEGACE) is associated with an increased risk of genital abnormalities in male fetuses (hypospadias). Second and third trimesters: Theoretical risk of adrenal suppression in the neonate due to progestational activity; however, data are limited. Use only if benefit outweighs risk. |
■ FDA Black Box Warning
Known or suspected pregnancy. Megestrol acetate can cause fetal harm when administered to a pregnant woman, and its use is contraindicated during pregnancy.
| Common Effects | Nausea Diarrhea Constipation Heartburn |
| Serious Effects |
["Known or suspected pregnancy","History of thromboembolic disease (relative contraindication)","Severe liver impairment (relative contraindication)","Allergy to megestrol acetate or any component of the formulation"]
| Precautions | ["Thromboembolic events (deep vein thrombosis, pulmonary embolism)","Adrenal suppression (possible HPA axis suppression, especially with chronic use)","Glucose intolerance (may exacerbate diabetes mellitus)","Fluid retention (use with caution in patients with cardiovascular disease)","Masking of signs of infection due to anti-inflammatory effects","Potential for tumor flare in hormone-sensitive cancers","Carcinogenicity (increased risk of breast cancer in dogs; unknown in humans)"] |
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| Fetal Monitoring | Monitor fetal growth and development via ultrasound if exposed during pregnancy. Assess for signs of adrenal suppression in the neonate (hypoglycemia, hyponatremia, hyperkalemia) after delivery if used near term. In mother, monitor for thromboembolic events (DVT, PE) due to progestin effects. |
| Fertility Effects | Megestrol acetate may disrupt normal menstrual cycles and ovulation due to its progestational and antigonadotropic effects. It can delay or inhibit ovulation, potentially impairing fertility temporarily. Effects are reversible upon discontinuation. |