What is the recommended dose of Megase (megestrol) for appetite stimulation?

Megestrol Acetate (Megace) Dosing for Appetite Stimulation

The FDA-approved and recommended dose of megestrol acetate for appetite stimulation is 800 mg/day (20 mL/day of oral suspension), which represents the optimal balance of efficacy and safety based on high-quality evidence. 1

Standard Dosing Regimen

The initial dose should be 800 mg/day taken as a single daily dose, which has demonstrated superior efficacy in multiple randomized controlled trials. 2, 1

• In clinical trials, 800 mg/day resulted in 64% of patients gaining five or more pounds, compared to 57% with 400 mg/day and only 24% with placebo 1
• Mean weight gain at 12 weeks was 7.8 pounds with 800 mg/day versus 4.2 pounds with 400 mg/day 1
• The liquid formulation is preferred over tablets as it is less expensive and more bioavailable 3

Dose-Response Evidence

Five dose-comparison trials demonstrated that the optimal dose range is between 480-800 mg per day, with 800 mg/day showing the greatest benefit. 2, 3

• A phase III trial comparing 160 mg, 480 mg, 800 mg, and 1,280 mg daily showed a positive dose-response effect for appetite stimulation (p = 0.02) 4
• The 800 mg dose appeared optimal, with no additional benefit from 1,280 mg/day 4
• Starting with 160 mg/day is a reasonable alternative in routine practice for cost considerations, with titration to 480-800 mg/day based on response 3

Alternative Dosing Strategies

For patients requiring a lower initial dose, start at 160-200 mg daily and titrate upward to 480-800 mg/day based on clinical response. 3, 5

• A moderate dose of 400 mg/day has shown efficacy with potentially fewer side effects in maintenance dialysis patients, with significant improvements in weight (9% increase), body fat (31% increase), and serum albumin (from 3.0 to 3.3 g/dL) over 16 weeks 6
• However, the 400 mg dose is less effective than 800 mg for cancer-related cachexia and should be reserved for specific populations or when tolerability is a concern 1, 6

Clinical Efficacy Expectations

Patients should be counseled that approximately 1 in 4 will experience appetite improvement and 1 in 12 will achieve meaningful weight gain. 3, 5

• 89% of patients on 800 mg/day showed appetite improvement versus 50% on placebo 1
• Weight gain is primarily adipose tissue rather than lean muscle mass 2, 3
• Clinical response typically occurs within 4-8 weeks of therapy 1

Critical Safety Warnings

Thromboembolic events occur in approximately 1 in 6 patients (RR 1.84), and mortality risk is increased (RR 1.42), requiring careful patient selection and monitoring. 3, 5

• Edema occurs with a relative risk of 1.36 3
• Other side effects include impotence, vaginal spotting, and potential adrenal suppression with long-term use 2, 3
• Regular assessment for thromboembolic phenomena is essential throughout treatment 3

Duration and Monitoring

Limit duration of therapy to short-term trials rather than indefinite use, with regular reassessment of whether continued therapy is warranted based on response and quality of life goals. 3

• Benefits should be weighed against risks, particularly for longer-term use 3
• Adrenal function should be monitored in patients on long-term therapy 3
• Weight changes should be assessed regularly to evaluate response 3

Clinical Context for Use

Megestrol acetate is most appropriate for patients with cancer-related anorexia/cachexia where increased appetite is an important quality of life goal and life expectancy is measured in months rather than weeks. 3

• Consider corticosteroids (dexamethasone 2-8 mg/day) as an alternative with similar appetite stimulation but different toxicity profile and lower cost 3
• Combination with olanzapine 5 mg/day may enhance weight gain (85% vs 41% when added to megestrol acetate) 3
• Do NOT use in patients with dementia, as evidence is limited and potential harms outweigh uncertain benefits 5