Is megestrol (Megace) associated with pulmonary embolism?

From the Guidelines

Yes, megestrol (Megace) is associated with an increased risk of pulmonary embolism.

Key Points

• The use of megestrol acetate has been shown to improve appetite and weight gain in patients with cancer-related anorexia/cachexia, but it also increases the risk of thromboembolic phenomena, including pulmonary embolism 1.
• According to a systematic review and meta-analysis, 1 in 6 patients treated with megestrol acetate will develop thromboembolic phenomena, and 1 in 23 will die 1.
• A Cochrane review of 35 trials comprising 3963 patients concluded that megestrol acetate resulted in higher rates of oedema, thromboembolic phenomena, and deaths compared to placebo 1.
• The optimal dose of megestrol acetate is between 480 and 800 mg per day, but the risk of thromboembolic phenomena remains a concern 1.
• Progestins, including megestrol acetate, may induce impotence, vaginal spotting, thromboembolism, and in some cases, death 1.

Important Considerations

• The benefits of megestrol acetate in improving appetite and weight gain must be weighed against the potential risks, including pulmonary embolism.
• Patients with advanced cancer undergoing chemotherapy and at risk of weight loss or malnourished may benefit from supplementation with long-chain N-3 fatty acids or fish oil to stabilize or improve appetite, food intake, lean body mass, and body weight 1.

From the FDA Drug Label

Postmarketing reports associated with megestrol acetate oral suspension include thromboembolic phenomena including thrombophlebitis and pulmonary embolism

• Pulmonary embolism is listed as a postmarketing report associated with megestrol acetate oral suspension.
• The FDA drug label directly supports the answer that megestrol (Megace) is associated with pulmonary embolism 2.

From the Research

Association with Pulmonary Embolism

• Megestrol acetate (Megace) has been associated with an increased risk of thromboembolic events, including pulmonary embolism, in some studies 3, 4, 5.
• A retrospective analysis of oncology patients using megestrol acetate concurrent with chemotherapy found that 11.3% of patients developed thrombosis, including pulmonary embolism 3.
• Another study found a positive correlation between the dose of estrogen and the risk of pulmonary embolism, and also found an excess of reports associated with the combination of ethinyloestradiol and megestrol acetate 4.
• A case review of geriatric patients treated with megestrol acetate reported two cases of deep vein thrombosis, and noted that thromboembolic events are potential adverse events associated with megestrol acetate therapy 5.

Mechanism and Risk Factors

• The exact mechanism by which megestrol acetate increases the risk of pulmonary embolism is not fully understood, but it may be related to its effects on blood clotting and fibrinolysis 4.
• Risk factors for pulmonary embolism in patients taking megestrol acetate may include advanced age, immobilization, and underlying medical conditions such as cancer or cardiovascular disease 3, 5.

Clinical Implications

• Healthcare providers should be aware of the potential risk of pulmonary embolism associated with megestrol acetate therapy, and monitor patients closely for signs and symptoms of thromboembolic events 3, 5.
• The benefits and risks of megestrol acetate therapy should be carefully weighed in individual patients, particularly those with risk factors for pulmonary embolism 4, 5.