Is a baseline electrocardiogram required before starting Korlym (mifepristone)?

Baseline EKG Recommendation for KORLYM (Mifepristone)

A baseline EKG is not absolutely required before starting KORLYM in all patients, but should be obtained in those with risk factors for QT prolongation, including hypokalemia, hypomagnesemia, congenital long QT syndrome, heart failure, bradyarrhythmias, or concurrent use of other QT-prolonging medications.

Risk Stratification Approach

The decision to obtain a baseline EKG before initiating KORLYM requires clinical risk assessment rather than universal screening 1:

High-Risk Patients Requiring Baseline EKG:

• Patients with hypokalemia or hypomagnesemia (particularly important since KORLYM itself causes hypokalemia in 44% of patients) 2
• Those already taking QT-prolonging medications
• Patients with congenital long QT syndrome
• Those with heart failure or coronary vascular disease 2
• Patients with bradyarrhythmias
• Elderly patients and women (higher baseline risk for acquired LQTS) 1

Low-Risk Patients Where Baseline EKG May Be Deferred:

• Otherwise healthy patients without the above risk factors
• Normal baseline electrolytes
• No concurrent QT-prolonging medications
• No structural heart disease

Monitoring Protocol

Before initiating KORLYM:

1. Correct hypokalemia before starting treatment 2
2. Obtain baseline EKG if any risk factors present 1
3. Check baseline electrolytes (potassium, magnesium)

After initiating KORLYM:

• Measure serum potassium 1-2 weeks after starting or increasing dose, then periodically 2
• If strong CYP3A inhibitors are used concurrently, obtain baseline EKG, repeat within one week of treatment initiation, and monitor as clinically indicated 3
• For patients requiring lower initiation doses due to risk factors, perform more frequent ECG monitoring with slower dose titrations 3

Important Clinical Considerations

QT Prolongation Risk: KORLYM prolongs the QTc interval in a dose-dependent manner 2. The risk increases when QTc exceeds 500 ms or when a drug increases QTc by >60-70 ms 1. If QTc increases to >480 ms during treatment, temporarily discontinue KORLYM 3.

Hypokalemia Management: This is critical because hypokalemia itself potentiates QT prolongation. KORLYM-induced hypokalemia should be treated with potassium supplementation; if persistent despite supplementation, add mineralocorticoid antagonists 2.

Drug Interactions: When combining KORLYM with strong CYP3A inhibitors (ketoconazole, itraconazole, ritonavir), limit dose to 900 mg daily maximum and implement enhanced ECG monitoring 2.

Common Pitfalls to Avoid

• Do not rely on cortisol levels to assess treatment response or adrenal insufficiency with KORLYM, as serum cortisol remains elevated during treatment 2
• Do not assume low risk in patients with Cushing's syndrome—they often have multiple cardiovascular comorbidities including hypertension and heart disease that increase QT risk 2
• Do not forget that elevated cortisol activates mineralocorticoid receptors in cardiac tissue, adding additional cardiac risk 2

The 2023 Canadian Cardiovascular Society guidelines emphasize that risk stratification and clinical judgment should guide ECG decisions rather than routine screening for all QT-prolonging medications 1. However, given KORLYM's known QT effects, dose-dependent prolongation, and the high-risk population (Cushing's patients with multiple comorbidities), a lower threshold for obtaining baseline ECG is warranted compared to lower-risk QT-prolonging drugs like sertraline 1.