What sort of EKG (electrocardiogram) changes should make me concerned when prescribing domperidone?

EKG Changes of Concern When Prescribing Domperidone

When prescribing domperidone, you should be concerned about QTc prolongation above 500 ms or an increase of >60 ms from baseline, as these changes significantly increase the risk of Torsades de Pointes (TdP) and sudden cardiac death. 1

Key EKG Changes to Monitor

• QTc interval >500 ms is considered dangerous and warrants immediate discontinuation of domperidone 1
• QTc prolongation >60 ms from baseline is a high-risk marker for TdP, even if the absolute QTc remains below 500 ms 1
• QTc interval >450 ms in males or >470 ms in females should raise concern and prompt reassessment of risk-benefit ratio 1, 2
• Distorted T-U wave morphology, especially after a pause, is an early warning sign of impending TdP 1
• Macroscopic T-wave alternans (beat-to-beat changes in T-wave amplitude or morphology) is a critical warning sign 1
• Onset of ventricular ectopy, particularly couplets or PVCs with short-long-short R-R cycle sequences 1

Risk Stratification for Domperidone-Induced QT Prolongation

High-Risk Patient Factors

• Female sex (higher baseline risk for QT prolongation) 1
• Advanced age (elderly patients are more vulnerable) 1, 3
• Electrolyte abnormalities, particularly hypokalemia, hypomagnesemia, or hypocalcemia 1
• Concurrent use of other QT-prolonging medications (occurs in approximately 70% of patients prescribed domperidone) 4
• Heart disease, especially congestive heart failure 1
• Bradycardia or heart block 1
• Impaired hepatic function (affects domperidone metabolism) 1

Medication Interactions of Concern

• Co-prescription with strong CYP3A4 inhibitors (increases domperidone concentration) 5, 3
• Concurrent use of other QT-prolonging drugs such as:
  • Antiarrhythmics (highest risk category) 1
  • Certain antibiotics (erythromycin) 1
  • Antipsychotics (thioridazine, haloperidol) 1
  • Antiemetics (ondansetron, palonosetron, granisetron) 1
  • Antidepressants (escitalopram, venlafaxine, sertraline, mirtazapine) 1

Monitoring Recommendations

• Obtain baseline ECG before starting domperidone to document QTc interval 1
• Correct any electrolyte abnormalities before initiating treatment 1
• Repeat ECG 7 days after starting treatment and after any dose changes 1
• Monitor more frequently if patient has additional risk factors 1
• Discontinue domperidone immediately if QTc exceeds 500 ms during treatment 1
• Consider periodic electrolyte monitoring, especially in patients on diuretics 1

Management of QT Prolongation

• If QTc >500 ms is detected, immediately discontinue domperidone 1
• For symptomatic TdP, administer 2g IV magnesium regardless of serum magnesium level 1
• Correct any electrolyte abnormalities 1
• Consider temporary cardiac pacing for TdP precipitated by bradycardia 1
• In emergency situations with TdP, non-synchronized defibrillation may be required 1

While a recent study suggests that domperidone at conventional doses (30-80 mg/day) was associated with QTc prolongation in only 6% of patients with none reaching clinically significant levels (>500 ms) 2, other research indicates that domperidone use is associated with a 3.8-fold increased risk of sudden cardiac death 5. The risk is particularly elevated when domperidone is co-prescribed with other QT-prolonging medications, which occurs in approximately 70% of patients 4.