What is the recommended use and dosage of Megace (megestrol acetate) for appetite stimulation and weight gain?

Megestrol Acetate (Megace) for Appetite Stimulation and Weight Gain

Megestrol acetate is recommended at a dosage of 400-800 mg/day for appetite stimulation and weight gain in patients with anorexia-cachexia syndrome, but should be monitored for thromboembolic events, fluid retention, and discontinued if ineffective after 4 weeks. 1

Indications and Efficacy

• Megestrol acetate is the most effective pharmacological appetite stimulant with evidence for weight gain in patients with:
  • Cancer-associated anorexia and cachexia
  • AIDS-related weight loss
  • Other underlying conditions causing appetite loss 1, 2
• Multiple clinical trials have demonstrated that megestrol acetate improves appetite and leads to non-fluid weight gain compared to placebo 2, 3
• Weight gain of 15 pounds or more was observed in 16% of patients receiving megestrol acetate compared to only 2% with placebo 3

Dosage Recommendations

• For appetite stimulation: 400-800 mg/day is the recommended dosage range 1
• The FDA-approved dosage for cancer treatment is different: 160 mg/day (40 mg four times daily) for breast cancer and 40-320 mg/day in divided doses for endometrial carcinoma 4
• A dose-response relationship exists for appetite stimulation, with higher doses generally producing better results 5, 6
• 800 mg/day appears to be the optimal dose for appetite stimulation, with no additional benefit observed at 1,280 mg/day 5
• For cost-effectiveness and convenience, starting at lower doses (160-400 mg/day) may be reasonable with dose escalation if needed 6

Administration and Duration

• Treatment should be continued for at least 2-4 weeks to determine efficacy 1, 4
• Patients should be weighed regularly to assess response to treatment 1
• Discontinue if ineffective after 4 weeks rather than continuing indefinitely 1
• Median time to peak weight during treatment is approximately 14 weeks 7

Monitoring and Side Effects

• Monitor for the following side effects:
  • Thromboembolic events (relative risk 1.84) 1
  • Edema and fluid retention (relative risk 1.36) 1, 3
  • Adrenal insufficiency with prolonged use 1
  • Increased mortality risk (relative risk 1.42) 1
• Deep vein thrombosis has been reported in clinical trials 7
• Generally well-tolerated compared to other appetite stimulants 3, 5

Combination Approach

• Megestrol acetate should be combined with non-pharmacological approaches:
  • Small, frequent meals (5-6 per day)
  • High-calorie, nutrient-dense foods
  • Pleasant eating environment
  • Moderate physical activity when appropriate 1

Alternative Pharmacological Options

If megestrol acetate is contraindicated or ineffective, consider:

• Dexamethasone (2-8 mg/day): Provides rapid appetite stimulation but should be limited in duration due to side effects 1
• Olanzapine (5 mg/day): Alternative with fewer thromboembolic risks but requires monitoring for metabolic side effects 1
• Mirtazapine (15-30 mg daily): May provide additional benefits for sleep difficulties or mood disorders 1
• Cannabinoids: Less effective than megestrol acetate but may be considered when other options have failed 1

Clinical Pearls and Pitfalls

• Megestrol acetate may reduce nausea and vomiting in addition to stimulating appetite 3
• Higher doses are associated with greater weight gain but also increased risk of side effects 5, 6
• Patients should be informed about the risks of thromboembolic events despite receiving palliative care 2
• Weight gain may take several weeks to manifest; patience with therapy is warranted 7