Which medications interact with Megace (megestrol acetate)?

Megestrol Acetate Drug Interactions

Megace (megestrol acetate) has minimal direct drug-drug interactions documented in clinical guidelines, but its glucocorticoid-like effects at higher doses require monitoring when combined with anticoagulants, antidiabetic agents, and other medications affecting thrombotic risk.

Key Interaction Considerations

Anticoagulant Therapy

• Patients on warfarin or other anticoagulants require heightened vigilance due to megestrol's significant thromboembolism risk (RR 1.84), with approximately 1 in 6 patients developing thromboembolic events including deep vein thrombosis and pulmonary embolism 1, 2
• The combination does not contraindicate megestrol use but necessitates more frequent INR monitoring and clinical assessment for thrombotic phenomena 1

Antidiabetic Medications

• Megestrol exhibits glucocorticoid-like effects at higher doses (480-800 mg/day), potentially causing hyperglycemia and insulin resistance 2, 3
• Patients on insulin or oral hypoglycemics may require dose adjustments of their diabetic medications when initiating megestrol therapy 2
• Blood glucose monitoring should be intensified, particularly during the first few weeks of treatment 3

Corticosteroids

• Concurrent use of megestrol with dexamethasone or other corticosteroids amplifies glucocorticoid effects, including adrenal suppression, hyperglycemia, and muscle wasting 1, 2
• While combination therapy is sometimes used intentionally (dexamethasone 2-8 mg/day as an alternative to megestrol), the additive effects require careful monitoring 1
• Adrenal function should be assessed in patients on long-term megestrol therapy, especially if corticosteroids are added 1, 2

Olanzapine (Synergistic Combination)

• Olanzapine 5 mg/day combined with megestrol acetate enhances weight gain (85% vs 41% achieving ≥5% weight gain) compared to megestrol alone 1, 2
• This represents a therapeutic interaction rather than an adverse one, though metabolic monitoring remains important 1

Medications Requiring Monitoring (Not Contraindications)

Agents Increasing Thrombotic Risk

• Estrogens, tamoxifen, and other hormonal therapies compound the already elevated thromboembolism risk with megestrol 1
• Chemotherapy agents themselves increase thrombotic risk; the combination requires vigilant assessment for venous thromboembolism 4

Immunosuppressants

• Megestrol's potential glucocorticoid activity may interact with other immunosuppressive agents, though specific interactions are not well-documented in guidelines 2

Clinical Monitoring Algorithm

For all patients initiating megestrol:

• Baseline assessment of thrombotic risk factors (prior VTE, malignancy type, immobility) 1
• Review current anticoagulation status and adjust monitoring frequency 1
• Assess baseline glucose control and adjust antidiabetic regimens proactively 2, 3
• Document concurrent corticosteroid use and plan adrenal function testing if long-term therapy anticipated 1, 2

During therapy:

• Regular assessment for thromboembolic phenomena (leg swelling, chest pain, dyspnea) at each visit 1, 2
• Monitor weight changes to assess response, recognizing gain is primarily adipose tissue 1, 2
• Reassess benefit versus risk after 12 weeks, particularly given mortality risk (RR 1.42) 1

Common Pitfalls to Avoid

• Do not assume megestrol is "safe" simply because formal drug interaction lists are short—the thrombotic and metabolic effects create functional interactions with multiple medication classes 1, 2
• Avoid initiating megestrol in patients with active thrombosis or recent VTE without compelling indication and concurrent anticoagulation 1
• Do not overlook the increased mortality risk (1 in 23 patients) when weighing combination therapies that may compound risks 1
• Remember that doses above 800 mg/day provide no additional benefit but increase glucocorticoid-like effects and potential interactions 1