What is the recommended dosage and frequency of Megestrol (megestrol acetate) for treating decreased appetite?

Megestrol Acetate Dosing for Decreased Appetite

For decreased appetite, start megestrol acetate at 800 mg daily (20 mL of oral suspension), taken once daily or divided into 400 mg twice daily with meals, based on the FDA-approved dosing and guideline recommendations. 1, 2

Initial Dosing Strategy

• The FDA-approved starting dose is 800 mg/day (20 mL/day) of oral suspension, which has been found clinically effective in trials 1
• The liquid formulation is preferred over tablets as it is less expensive and more bioavailable 2
• Doses between 480-800 mg/day appear optimal for appetite stimulation, with higher doses associated with greater weight improvement 3, 2
• If gastrointestinal side effects occur, divide the dose to 400 mg twice daily with meals (breakfast and dinner) to improve tolerability 4

Dose Adjustment Approach

• Evaluate response after 2 weeks of therapy - the majority of patients who respond do so within 15 days 5
• If no response at 800 mg/day after 2-4 weeks, consider dose escalation to 480-800 mg/day range, though evidence suggests doses above 480 mg/day provide minimal additional benefit 5
• Lower doses (160-320 mg/day) have been studied but show less consistent appetite and weight improvement compared to higher doses 5
• A moderate dose of 400 mg/day has shown efficacy with fewer side effects in some populations, particularly for maintenance therapy 6, 7

Critical Safety Considerations

You must weigh serious risks against modest benefits before prescribing:

• 1 in 6 patients will develop thromboembolic events (relative risk 1.84), including deep vein thrombosis and pulmonary embolism 2
• 1 in 23 patients will die from treatment-related complications (relative risk 1.42 for mortality) 2
• 1 in 4 patients will experience appetite improvement and only 1 in 12 will gain weight 2
• Weight gain is primarily adipose tissue, not muscle mass, limiting functional benefit 3, 8
• Edema occurs with relative risk of 1.36 2

Monitoring Requirements

• Assess for thromboembolic phenomena regularly throughout treatment due to significantly elevated risk 3, 8
• Monitor weight changes to assess response, though recognize this reflects fat gain rather than lean body mass 8
• Check adrenal function in patients requiring long-term therapy (beyond several months) 3, 8
• Evaluate for edema development 2

Duration of Therapy

• Limit duration to short-term trials (weeks to months) rather than indefinite use 2
• Consider discontinuation after 2-4 weeks if no appetite improvement occurs 5
• The benefits must be reassessed against risks, particularly for longer-term use beyond several months 3
• Corticosteroid-like effects limit long-term use, especially in patients with longer life expectancy 8

Clinical Context for Use

Megestrol is most appropriate for:

• Patients with cancer-related anorexia/cachexia where increased appetite is an important quality of life goal 2
• Patients with months-to-weeks or weeks-to-days life expectancy 2
• Situations where reversible causes of anorexia (oral candidiasis, depression, pain, constipation, nausea) have been addressed first 2

Megestrol should NOT be used for:

• Patients with dementia and reduced appetite - evidence is insufficient and risks outweigh uncertain benefits 2
• Routine management of cachexia without careful risk-benefit assessment 2

Alternative Considerations

• Corticosteroids (dexamethasone 3-4 mg/day equivalent) provide similar appetite stimulation with different toxicity profile and lower cost ($27 vs $57 per month) 2
• Combination therapy with olanzapine plus megestrol showed superior weight gain (85% vs 41%) in one trial, though this requires further validation 2
• Cannabinoids (dronabinol) are inferior to megestrol for appetite stimulation in cancer patients 2