What are the main side effects of Megace (megestrol acetate)?

Main Side Effects of Megestrol Acetate (Megace)

The main side effects of megestrol acetate (Megace) include thromboembolic events, weight gain (primarily as fat tissue rather than muscle), edema, adrenal suppression, and increased mortality risk. 1, 2

Common Side Effects

Megestrol acetate causes several significant side effects that require monitoring:

• Thromboembolic phenomena (RR 1.84)

  • Thrombophlebitis
  • Pulmonary embolism (potentially fatal)
  • Requires screening for risk factors before initiation 2, 1

• Weight gain

  • Primarily due to increased fat mass (not muscle)
  • Partly due to edema
  • Associated with increased appetite 1, 3

• Endocrine effects

  • Hyperglycemia and glucose intolerance
  • Adrenal suppression (glucocorticoid-like effects) 1

• Cardiovascular effects

  • Edema (RR 1.36)
  • Heart failure
  • Hypertension 2, 1

Less Common Side Effects

Additional adverse reactions that may occur with megestrol acetate include:

• Gastrointestinal: Nausea and vomiting 1
• Neurological: Carpal tunnel syndrome, mood changes, lethargy 1
• Dermatological: Alopecia, rash, sweating 1
• Respiratory: Dyspnea 1
• Gynecological: Breakthrough menstrual bleeding 1
• Constitutional: Hot flashes, malaise, asthenia 1

Monitoring Recommendations

Due to these significant side effects, patients on megestrol acetate should be monitored for:

• Thromboembolic events (highest risk)
• Weight and edema assessment
• Blood glucose levels
• Cardiovascular status 2

Clinical Considerations

The risk-benefit profile of megestrol acetate must be carefully considered:

• While it effectively stimulates appetite and causes weight gain, this weight gain is primarily adipose tissue rather than skeletal muscle 4, 3
• The increased mortality risk (RR 1.42) associated with megestrol acetate is significant 2
• Effectiveness should be assessed after 2-4 weeks of therapy, and the medication should be discontinued if no improvement in appetite or weight is observed 2

Dosing and Side Effect Relationship

Side effects may be dose-dependent:

• Standard doses for appetite stimulation range from 400-800mg daily 2
• Higher doses may increase risk of adverse effects
• Some studies have shown that moderate doses (400mg/day) may still be effective while potentially reducing side effect burden 5

The weight gain from megestrol acetate, while often desired in cancer and AIDS patients with cachexia, does not typically translate to improved functional status as measured by Karnofsky index, since the gain is primarily fat and fluid rather than muscle mass 6, 3.

Megestrol acetate should be used cautiously, with careful consideration of the patient's thromboembolic risk factors and expected survival, as the side effect profile can significantly impact morbidity and mortality.