Megestrol Acetate Dosing Recommendations
For cancer-related anorexia/cachexia, megestrol acetate should be dosed at 400-800 mg per day orally, with the FDA-recommended initial dosage being 800 mg/day (20 mL/day) of the oral suspension. 1
Dosing by Indication
Cancer-Related Anorexia/Cachexia
- Initial dose: 800 mg/day (20 mL/day) of oral suspension 1
- Effective dose range: 400-800 mg/day 2, 1
- Clinical trials comparing different dose schedules found that 400 and 800 mg/day were both clinically effective 1
- Optimal dose appears to be between 480 and 800 mg/day based on comparative trials 2
- Lower doses (80 mg twice daily) may be considered as a starting dose in some patients, with potential for dose escalation if needed 3
Administration Considerations
- Oral suspension should be shaken well before using 1
- Liquid formulation may be less expensive and more bioavailable than tablets 2
- For twice-daily dosing, administration after meals may be beneficial 3
Evidence Quality and Efficacy
- Megestrol acetate has been studied in more than 30 randomized clinical trials 2
- High-level evidence supports its use for appetite stimulation in cancer patients 2
- Benefits include improved appetite and weight gain, though primarily through increased fat mass rather than lean body mass 2, 4
- In a meta-analysis of 23 trials with 3,436 cancer patients, megestrol acetate doses of 160-1600 mg/day for 2 weeks to 2 years showed favorable results for appetite and weight gain compared to placebo 2
Potential Adverse Effects
- Common side effects include edema, thromboembolism, and adrenal insufficiency 2
- Higher doses are associated with increased risk of death (RR, 1.42), thromboembolic events (RR, 1.84), and edema (RR, 1.36) 2
- Cortisol suppression is common at higher doses and may be persistent, though clinical symptoms of adrenal insufficiency are rare 5
- Drug interactions: Megestrol is contraindicated with concomitant use of dofetilide due to risk of QT prolongation 2
Special Populations
Renal Impairment
- Moderate doses (400 mg/day) have been used safely in hemodialysis patients to improve nutritional status and appetite 6, 4
- In dialysis patients, 400 mg/day for 16 weeks improved nutritional parameters without major side effects 6
Elderly Patients
- Doses of 400-800 mg daily have shown improvements in prealbumin levels in elderly patients with poor appetite after hospitalization 5
- Cortisol suppression is dose-dependent and more common at higher doses (70% at 400 mg, 78% at 800 mg) 5
Clinical Decision Making
- For patients with advanced cancer and anorexia/cachexia, start with 800 mg/day (FDA recommendation) 1
- For elderly or frail patients, consider starting at 400 mg/day and titrate based on response 5
- For patients with renal impairment, 400 mg/day appears to be both effective and well-tolerated 6
- Monitor for adverse effects, particularly edema and thromboembolic events 2
- Consider discontinuation if no improvement in appetite is seen after 4-8 weeks of therapy 2
Important Considerations
- Megestrol acetate increases weight primarily through fat mass, not lean body mass 2, 4
- The medication should not be used with dofetilide due to drug interactions 2
- ASCO guidelines recommend megestrol acetate as a pharmaceutical option for management of cancer cachexia 2
- NCCN Palliative Care guidelines list megestrol acetate (400-800 mg/day) as an appetite stimulant option for patients with anorexia/cachexia 2