Is it safe to use mifepristone with Imdur (isosorbide mononitrate)?

Mifepristone and Imdur (Isosorbide Mononitrate) Combination

There is no documented drug-drug interaction between mifepristone and Imdur (isosorbide mononitrate), but mifepristone requires careful review of all concomitant medications due to its potential for drug interactions, and should only be prescribed by clinicians with extensive experience in managing Cushing's disease. 1, 2

Key Safety Considerations

Drug Interaction Screening Required

• All concomitant medications must be carefully reviewed when mifepristone is prescribed, as it has significant potential for drug-drug interactions. 1
• The Endocrine Society emphasizes that careful evaluation of drug interactions is essential before prescribing mifepristone. 2
• Mifepristone should be used cautiously and only by expert pituitary endocrinologists who can properly monitor for interactions and complications. 1, 2

No Specific Contraindication with Nitrates

• The available evidence does not identify isosorbide mononitrate (Imdur) as having a specific interaction with mifepristone. 1
• Imdur is a sustained-release nitrate used for angina prophylaxis with a well-established safety profile. 3, 4

Clinical Context for Mifepristone Use

Primary Indication

• Mifepristone is FDA-approved specifically for hyperglycemia associated with Cushing's syndrome, not for general use. 1, 2
• It should only be considered when other first-line agents (osilodrostat, metyrapone, ketoconazole) are inappropriate or have failed. 2, 5

Critical Monitoring Limitations

• No laboratory markers of efficacy exist with mifepristone—cortisol levels cannot be used to monitor treatment response or adrenal insufficiency. 1, 2
• Only clinical features can guide management, making this medication challenging to use outside specialized practice. 1
• The long half-life of mifepristone complicates management of adrenal insufficiency, requiring several days of stress-dose glucocorticoid replacement (preferably dexamethasone). 2

Cardiovascular Considerations

Hypertension Management

• If the patient requires both mifepristone (for Cushing's disease) and Imdur (for angina), these conditions should be managed with appropriate medications for each indication rather than expecting one drug to address both. 5
• Mifepristone can paradoxically increase blood pressure in some patients (12 patients in clinical trials showed increased blood pressure, 9 with hypokalemia requiring spironolactone). 1
• Close monitoring of blood pressure and potassium is essential when using mifepristone. 1

Common Pitfalls to Avoid

• Do not prescribe mifepristone without extensive experience in Cushing's disease management. 2
• Do not rely on cortisol measurements for monitoring efficacy or safety. 1, 2
• Do not overlook the need for comprehensive medication review before initiating mifepristone. 1, 2
• Monitor for hypokalemia and mineralocorticoid receptor activation, which may require spironolactone addition. 1
• Be aware that thyroid function should be closely monitored and thyroid hormone replacement adjusted as needed during mifepristone treatment. 1