Recommended Dose of Megestrol Acetate (Megace)
The FDA-approved and guideline-recommended dose of megestrol acetate for cancer-related anorexia/cachexia is 400-800 mg/day orally, with 800 mg/day being the standard initial dose. 1, 2
Standard Dosing Regimen
- Start with 800 mg/day (20 mL/day of standard oral suspension) as the FDA-approved initial dose for appetite stimulation in cancer-related anorexia and cachexia 1
- The NCCN Palliative Care guidelines recommend 400-800 mg/day for patients with anorexia/cachexia and life expectancy of year-to-months 2
- ASCO guidelines list 200-600 mg/day as the suggested dosing range, though this represents a more conservative approach 2
Optimal Dosing Based on Evidence
- The optimal dose appears to be between 480-800 mg/day based on comparative trials showing the best balance of efficacy and safety 3, 4
- Doses of 400 mg/day and 800 mg/day were both found to be clinically effective in FDA trials 1
- Higher doses up to 1,600 mg/day have been studied, but doses above 480 mg/day show diminishing additional benefit while increasing risks 3
Formulation Considerations
- Use the liquid formulation rather than tablets as it is less expensive and more bioavailable 2, 4
- A concentrated nanocrystal dispersion formulation (625 mg/5 mL) allows for once-daily dosing of 5 mL instead of 20 mL, improving convenience 5, 6
Dose Titration Strategy
- A reasonable approach is to start at 400 mg/day and titrate up to 800 mg/day based on response 3
- This balances efficacy with cost and side effect profile 3
- Assess response after 2-4 weeks and adjust accordingly 4
Critical Safety Warnings
Before prescribing, patients must understand these risks:
- 1 in 6 patients will develop thromboembolic events (deep vein thrombosis, pulmonary embolism) with a relative risk of 1.84 3
- 1 in 23 patients will die from treatment-related complications with a relative risk of 1.42 for mortality 3
- Only 1 in 4 patients will experience appetite improvement, and only 1 in 12 will gain weight 3
- Weight gain is primarily adipose tissue, not skeletal muscle, limiting functional benefit 3
- Edema occurs with relative risk of 1.36 3
- Adrenal insufficiency can develop with long-term use 3
Special Population Dosing
Dialysis patients require lower doses:
- Use 400 mg/day (not 800 mg/day) in maintenance dialysis patients to avoid excessive side effects 7
- The standard 800 mg/day dose is too high for end-stage renal disease patients and carries unacceptable risks 8
Duration and Monitoring
- Limit duration to short-term trials rather than indefinite use due to mortality and thromboembolic risks 3
- Regularly reassess whether continued therapy is warranted based on response and quality of life goals 3
- Monitor for thromboembolic phenomena, edema, and adrenal function with long-term use 3
Clinical Context for Use
- Megestrol acetate is most appropriate when increased appetite is an important quality of life goal in patients with life expectancy 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 ($27.11/month vs $57.41/month) 2
- Combination with olanzapine 5 mg/day may enhance weight gain (85% vs 41% response rate) 2, 3