MEGESTROL ACETATE

Clinical safety rating: avoid

Positive evidence of fetus risks but benefits may outweigh risks in some cases

How it works

Synthetic progestin with antineoplastic activity; suppresses pituitary gonadotropin secretion and exerts direct cytotoxic effects on endometrial cancer cells via binding to progesterone receptors. Also stimulates appetite through unclear mechanisms, possibly involving neuropeptide Y and inhibition of proinflammatory cytokines.

What the body does with it

Metabolism	Primarily hepatic via hydroxylation and conjugation; metabolites excreted in urine and bile. CYP3A4 is the major enzyme involved.
Excretion	Renal: 50-79% as glucuronide conjugates; fecal: 8-30%; biliary: minor.
Half-life	Terminal half-life: 13-105 hours (mean ~34 hours) in adults; prolonged in hepatic impairment.
Protein binding	90% bound primarily to albumin.
Volume of Distribution	Vd: 1.2-1.6 L/kg; extensive tissue distribution including adipose and muscle.
Bioavailability	Oral: 70-98% (mean ~90%); no parenteral formulations.
Onset of Action	Oral: 4-6 hours for appetite stimulation; no parenteral route approved.
Duration of Action	Appetite stimulation persists for 4-8 weeks after discontinuation due to tissue accumulation.

Classification & Brands

Dosing & administration

400 mg orally once daily or 800 mg orally once daily (suspension) for appetite stimulation; 40-320 mg orally daily in divided doses for endometrial cancer.

Dosage form	TABLET
Renal impairment	No dose adjustment required for GFR ≥30 mL/min; use with caution and monitor for fluid retention if GFR <30 mL/min.
Liver impairment	Mild to moderate hepatic impairment (Child-Pugh A-B): no adjustment; severe hepatic impairment (Child-Pugh C): use with caution, consider dose reduction by 50% and monitor for adverse effects.
Pediatric use	For appetite stimulation: initial dose 7.5-15 mg/kg/day orally in divided doses; maximum 800 mg/day. Not approved for endometrial cancer in children.
Geriatric use	Initiate at lower end of dosing range (e.g., 400 mg orally once daily); monitor for fluid retention, thromboembolic events, and glucose intolerance more frequently.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Can increase the effects of warfarin Can cause thromboembolic phenomena and adrenal suppression.

Breastfeeding	Excreted in human breast milk; M/P ratio not established. Potential for adverse effects in nursing infants (e.g., hormonal disturbances, weight gain). Use during breastfeeding is not recommended, especially during first 30 days postpartum and in infants with hepatic dysfunction.
Teratogenic Risk	Pregnancy category X. First trimester: high risk of masculinization of female fetuses (clitoral hypertrophy, labial fusion) due to androgenic activity. Second and third trimesters: possible increased risk of genital abnormalities and potential for long-term hormonal effects; use contraindicated in pregnancy for any indication.

Warnings & precautions

■ FDA Black Box Warning

Not approved for use in dementia-related weight loss due to increased risk of mortality, cerebrovascular events, and venous thromboembolism.

Side Effect Profile

Common Effects	breast cancer
Serious Effects

Absolute Contraindications

["Known hypersensitivity to megestrol acetate or any component","Pregnancy","Active thromboembolic disease (e.g., deep vein thrombosis, pulmonary embolism)"]

Clinical Precautions

Precautions

["Thromboembolic events: increased risk of deep vein thrombosis, pulmonary embolism, and stroke","Use in pregnancy: may cause fetal harm; effective contraception required","Fluid retention and worsening of hypertension or heart failure","Adrenal suppression: potential for hypothalamic-pituitary-adrenal axis suppression","Glucose intolerance: may exacerbate diabetes mellitus","Increased risk of cerebrovascular events in elderly patients with dementia"]

Clinical Tips & Counseling

Drug interactions

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