What is the starting dose of megestrol (megestrol acetate) for appetite stimulation?

Starting Dose of Megestrol Acetate for Appetite Stimulation

The recommended starting dose of megestrol acetate for appetite stimulation in cancer patients is 160 mg per day, which can be increased to 480-800 mg per day if needed for optimal effect. 1

Dosing Guidelines

Initial Dosing

• Start with 160 mg/day (can be given as 80 mg twice daily after meals) 1, 2
• This lower starting dose balances efficacy with cost and potential side effects
• Monitor response for 2-4 weeks before considering dose adjustment

Dose Titration

• If inadequate response at initial dose, increase to 480 mg/day 1
• Maximum effective dose appears to be 800 mg/day 1, 3
• Doses above 800 mg/day show minimal additional benefit but increased cost 1, 3

Evidence Supporting Dosing Recommendations

The ESPEN guidelines on nutrition in cancer patients (2017) analyzed over 30 randomized clinical trials of progestins and found that megestrol acetate at doses of 160-1600 mg/day improved appetite and weight gain compared to placebo 1. Five trials comparing different doses suggested that the optimal dose range is between 480-800 mg/day 1.

A phase III trial specifically evaluating four different doses (160,480,800, and 1,280 mg/day) demonstrated a positive dose-response effect for appetite stimulation, with 800 mg/day appearing optimal 3. However, considering cost and convenience factors, starting at 160 mg/day is reasonable for initial treatment 4.

Clinical Considerations

Patient Populations

• Indicated primarily for anorexia/cachexia in advanced cancer patients 1
• Can be used after failure of dietetic and oral nutritional management 1

Administration

• Can be administered as divided doses (e.g., 80 mg twice daily) 2
• Take after meals when possible 2

Monitoring

• Assess appetite improvement and weight gain at regular intervals
• The NCCN Palliative Care guidelines recommend megestrol acetate 400-800 mg/day for patients with anorexia/cachexia with life expectancy of months to years 1

Potential Side Effects and Cautions

• Thromboembolic events: Increased risk (monitor for DVT/PE) 1
• Edema: Common side effect 1, 5
• Impotence and vaginal spotting: Possible hormonal effects 1
• Mortality: Higher rates of death have been reported in some studies 1

Alternative Agents

If megestrol acetate is ineffective or contraindicated, consider:

• Dexamethasone 2-8 mg/day 1
• Olanzapine 5 mg/day 1
• Combination therapy (olanzapine plus megestrol acetate has shown superior weight gain compared to megestrol alone) 1

Key Practice Points

• Start low (160 mg/day) and titrate as needed up to 800 mg/day
• Weigh benefits against potential serious side effects, particularly thromboembolic risk
• Monitor for weight gain that is not solely due to fluid retention
• Expect appetite improvement to precede weight gain
• Consider discontinuing if no benefit after 4-8 weeks of optimal dosing