Side Effects of Megace (Megestrol Acetate)
Megestrol acetate (Megace) can cause serious side effects including thromboembolic events, edema, and death, and should only be used in appropriate clinical contexts such as cancer-related anorexia when benefits outweigh risks.
Common Side Effects
- Weight gain - This is one of the most frequent side effects, associated with increased appetite but not necessarily fluid retention 1
- Thromboembolic phenomena - Including thrombophlebitis and pulmonary embolism (sometimes fatal) 1, 2
- Edema - Fluid retention has been reported as a significant side effect 1, 2
Serious Adverse Events
- Increased mortality risk - A Cochrane review found megestrol acetate was associated with higher rates of death compared to placebo (RR, 1.42; 95% CI, 1.04 to 1.94) 2
- Thromboembolic events - Significantly increased risk (RR, 1.84; 95% CI, 1.07 to 3.18) 2
- Adrenal suppression - Can lead to glucocorticoid effects 1
Endocrine and Metabolic Effects
- Hyperglycemia and glucose intolerance - May affect blood sugar control 1
- Breakthrough menstrual bleeding - Hormonal effects can cause vaginal spotting 1, 2
- Impotence - Sexual dysfunction has been reported 2
Cardiovascular Effects
- Heart failure - Has been reported as an adverse reaction 1
- Hypertension - Blood pressure elevation can occur 1
Gastrointestinal Effects
- Nausea and vomiting - Common gastrointestinal side effects 1
Neurological and Psychiatric Effects
- Mood changes - Alterations in mood have been reported 1
- Carpal tunnel syndrome - Neurological complications can occur 1, 3
- Lethargy, malaise, and asthenia - General feelings of weakness and fatigue 1
Other Side Effects
- Hot flashes - Paradoxically, despite being used to treat hot flashes in some contexts 3
- Sweating and rash - Dermatological effects 1
- Alopecia - Hair loss has been reported 1
- Dyspnea - Breathing difficulties can occur 1
- Tumor flare - With or without hypercalcemia 1
Clinical Context and Risk Assessment
- Benefit-risk assessment - While megestrol acetate improves appetite and can increase body weight in cancer cachexia patients, the weight gain is primarily adipose tissue rather than skeletal muscle 2
- Dosing considerations - Optimal dosing for appetite stimulation in cancer patients appears to be between 480-800 mg per day, with higher doses associated with greater improvement in weight 2
- Duration of treatment - Corticosteroid-like effects limit long-term use, particularly in patients with longer life expectancy 2
Special Populations
- Children - Limited studies suggest megestrol acetate may be well-tolerated with fewer side effects in pediatric cancer patients with malnutrition 4
- Advanced cancer patients - May experience improved appetite, weight gain, and well-being despite minimal tumor response 5
Monitoring Recommendations
- Regular assessment for thromboembolic phenomena is essential due to the significant increased risk 2
- Monitor for fluid retention and edema, particularly in patients with cardiac risk factors 1
- Assess adrenal function in patients on long-term therapy 2
- Monitor weight changes, as weight gain is common but not necessarily indicative of improved muscle mass 2