What is the recommended dose and sig (prescription instructions) for megestrol acetate (megestrol) in an elderly patient with decreased appetite due to frailty or malnutrition?

Megestrol Acetate Dosing for Appetite Stimulation in Elderly Frail Patients

For elderly patients with decreased appetite due to frailty or malnutrition, megestrol acetate 400-800 mg daily is the recommended dose, taken as a single daily dose or divided throughout the day, with a minimum treatment duration of 2 months to assess efficacy. 1, 2

Specific Dosing Recommendations

Standard Dosing

• Start with 400 mg daily as the initial dose for appetite stimulation 1, 3
• The minimum effective dose is 160 mg/day, with no additional benefit demonstrated above 480 mg/day 4
• Maximum recommended dose is 800 mg daily 1, 5
• Administer as a single daily dose or divided into multiple doses throughout the day 2

Expected Outcomes and Timeline

• Approximately 1 in 4 patients (25%) will experience improved appetite 1
• Only about 1 in 12 patients (8%) will achieve modest weight gain 1
• Require at least 2 months of continuous treatment to determine efficacy 2
• At 20 days, prealbumin levels increase in a dose-dependent manner, with 400 mg and 800 mg doses showing significant improvement compared to placebo 5

Critical Safety Warnings for Elderly Patients

Adrenal Suppression (Most Important Concern)

• At 400 mg daily, 70% of elderly patients develop morning cortisol levels below 8 ng/mL (lower limit of normal) by day 20 5
• At 800 mg daily, 78% develop cortisol suppression by day 20 5
• Cortisol suppression may persist: at 63 days, 30% of patients on 400 mg and 56% on 800 mg still have suppressed levels 5
• Adrenal insufficiency can present as hypotension, weakness, and respiratory compromise requiring intensive care 6
• Monitor for clinical signs of adrenal insufficiency throughout treatment 6

Thromboembolic Risk

• Megestrol acetate increases risk of deep vein thrombosis and thromboembolic events 1, 7
• Use with extreme caution in patients with history of thromboembolic disease 2
• Common additional side effects include edema, impotence, and vaginal spotting 3

Mortality Concerns

• One Cochrane review found higher death rates in megestrol acetate groups compared to placebo 3
• After 44 months of treatment, decreased median survival was observed 7
• Over 25 weeks, no increased mortality was noted, but longer-term use raises concerns 7

When NOT to Use Megestrol Acetate

Absolute Contraindications

• Do NOT use in patients with dementia who lack concurrent depression - evidence shows no consistent benefit and potentially harmful side effects outweigh uncertain benefits 3, 4
• Avoid in patients where weight gain would be detrimental (obesity, cardiovascular disease, metabolic syndrome) 4

Preferred Alternative: Mirtazapine

• For elderly patients with concurrent depression and appetite loss, use mirtazapine 7.5-15 mg at bedtime instead 3, 4
• Mirtazapine offers dual benefit of treating depression while stimulating appetite 4
• One retrospective study showed mean weight gain of 1.9 kg at 3 months and 2.1 kg at 6 months, with 80% experiencing some weight gain 3

Monitoring Requirements

Essential Monitoring Parameters

• Assess weight and appetite weekly initially, then regularly throughout treatment 4
• Monitor for signs of adrenal insufficiency (hypotension, weakness, fatigue) 5, 6
• Watch for thromboembolic events (leg swelling, chest pain, shortness of breath) 7
• Check for edema and fluid retention 3
• Regular reassessment of benefit versus harm is essential 1, 3

Special Considerations for Elderly

• Start at the low end of the dosing range (400 mg daily) for elderly patients 2
• Greater frequency of decreased hepatic, renal, or cardiac function requires cautious dosing 2
• Megestrol acetate is substantially excreted by the kidney; risk of toxic reactions is greater in patients with impaired renal function 2
• Monitor renal function in elderly patients 2

Clinical Decision Algorithm

1. First, rule out treatable causes of poor appetite (medication side effects, depression, metabolic disorders) 3
2. If depression is present or suspected, choose mirtazapine 7.5-15 mg at bedtime instead of megestrol acetate 3, 4
3. If dementia without depression, do NOT use any appetite stimulants - focus on non-pharmacological approaches 3, 4
4. For frail elderly without depression or dementia, start megestrol acetate 400 mg daily 1, 3
5. Monitor closely for adrenal suppression and thromboembolic events 5, 7, 6
6. Reassess at 2 months; if no benefit, discontinue 2
7. If continuing beyond 9 months, consider dose reduction to reassess need 4

Important Caveats

• Megestrol acetate may attenuate benefits of resistance training, causing smaller gains or deterioration in muscle strength and functional performance 3
• The drug does not increase fat-free mass, only total body weight 3
• Consistent, meaningful weight gain is not reliably observed across studies 7
• Non-pharmacological approaches (oral nutritional supplements, social dining, frequent small meals) should be implemented first 8, 1