What is the recommended dosing of Megace (megestrol acetate) for a patient with cancer-related cachexia or AIDS-related anorexia?

Megestrol Acetate (Megace) Dosing

For cancer-related anorexia/cachexia, start megestrol acetate at 400-800 mg orally once daily, with 800 mg/day showing superior efficacy in clinical trials. 1, 2

Standard Dosing Regimens

Cancer-Related Anorexia/Cachexia

• Recommended dose: 400-800 mg/day orally for patients with life expectancy measured in year-to-months 1
• Optimal dose: 800 mg/day demonstrates the highest efficacy, with 64% of patients achieving ≥5 pound weight gain versus 24% with placebo 2
• Mean weight gain at 800 mg/day is 7.8-11.2 pounds over 12 weeks 2
• Alternative starting approach: Begin at 160 mg/day and titrate up to 480-800 mg/day based on response, though this is less supported than starting at 800 mg/day 3

AIDS-Related Anorexia/Cachexia

• FDA-approved dose: 800 mg/day (20 mL of 40 mg/mL suspension) for AIDS-related weight loss 2
• Concentrated formulation available: 625 mg/5 mL (one teaspoon daily) provides equivalent bioavailability with improved convenience 4, 5

Formulation Considerations

• Liquid suspension is preferred over tablets due to lower cost and superior bioavailability 3
• Standard suspension: 40 mg/mL (800 mg = 20 mL daily) 2
• Concentrated suspension: 625 mg/5 mL (single teaspoon daily) 4

Clinical Efficacy Expectations

Response Rates at 800 mg/day

• 1 in 4 patients (25%) will experience appetite improvement 3, 6
• 1 in 12 patients (8%) will achieve measurable weight gain 3
• 89% report improved appetite at last evaluation during 12-week trials 2
• Weight gain is primarily adipose tissue, not skeletal muscle, which limits functional benefit 3, 7

Critical Safety Warnings

Major Risks (Must Counsel Patients)

• 1 in 6 patients (17%) will develop thromboembolic events including deep vein thrombosis and pulmonary embolism (RR 1.84) 3, 7
• 1 in 23 patients (4%) will die from treatment-related complications (RR 1.42 for mortality) 3
• Edema occurs with RR 1.36 compared to placebo 3, 7

Monitoring Requirements

• Regular assessment for thromboembolic phenomena (leg swelling, chest pain, shortness of breath) 3, 7
• Weight monitoring every 2-4 weeks to assess response 7
• Adrenal function monitoring for long-term therapy (>3 months) due to glucocorticoid-like effects at higher doses 3, 7

Duration of Therapy

• Limit duration to short-term trials rather than indefinite use due to cumulative risks 3
• Reassess benefit versus risk regularly, particularly after 12 weeks 3
• Consider discontinuation if no appetite improvement or weight gain after 4-8 weeks 1

Alternative and Combination Strategies

When to Consider Alternatives

• Dexamethasone 2-8 mg/day offers similar appetite stimulation with different toxicity profile (muscle wasting, hyperglycemia, infection risk) and significantly lower cost 1, 3
• Dexamethasone should be restricted to 1-3 weeks maximum due to cumulative toxicity 3
• Olanzapine 5 mg/day can be used as monotherapy or added to megestrol acetate 1

Combination Therapy

• Megestrol acetate 800 mg/day + olanzapine 5 mg/day showed superior weight gain (85% vs 41% achieving ≥5% weight gain) in one trial 3, 7
• Multi-agent regimens including L-carnitine, celecoxib, and antioxidants have shown improved lean body mass and quality of life in phase III trials 1

Cannabinoids

• Cannabinoids (dronabinol) are inferior to megestrol acetate for appetite stimulation in cancer patients and should not be first-line 3

Patient Selection Criteria

Appropriate Candidates

• Patients with cancer-related anorexia/cachexia where increased appetite is an important quality of life goal 3, 7
• Life expectancy measured in months rather than weeks 1, 3
• No active thromboembolic disease or high bleeding risk 3

Contraindications/Cautions

• Active thrombophlebitis or thromboembolic disorders 3
• History of bleeding disorders or benign prostatic hyperplasia (BPH) 3
• Patients requiring preservation of lean body mass should consider resistance exercise programs as adjunct 3

Common Pitfalls to Avoid

• Do not use in dying patients (weeks-to-days life expectancy) where risks outweigh benefits 1
• Do not expect functional improvement from weight gain, as it is primarily fat, not muscle 3, 7
• Do not continue indefinitely without reassessment of benefit versus cumulative risk 3
• Do not use doses below 400 mg/day as efficacy is significantly reduced 2, 8