Domperidone and Propranolol Drug Interaction
The combination of domperidone and propranolol carries significant cardiac risk due to additive QTc prolongation effects and should be avoided or used with extreme caution with mandatory ECG monitoring. 1
Primary Cardiac Concerns
QTc Prolongation Risk
- Domperidone prolongs the QTc interval and requires long-term ECG monitoring when used chronically, as highlighted by National Patient Safety Agency alerts 1
- Propranolol, as a non-selective beta-blocker, can also affect cardiac conduction and rhythm 1
- The combination creates additive risk for potentially fatal cardiac arrhythmias, similar to the mechanism that led to cisapride's withdrawal from the market 1
Hemodynamic Complications
- Beta-blockers like propranolol can cause bradycardia, hypotension, and cardiac conduction abnormalities 2, 3
- When combined with domperidone's QTc effects, patients face compounded risk of serious arrhythmias
- This interaction is particularly dangerous in patients with pre-existing cardiac conditions, electrolyte abnormalities, or those taking other QT-prolonging medications 1
Clinical Management Algorithm
Before Prescribing This Combination:
- Obtain baseline ECG to assess QTc interval - do not proceed if QTc >450 ms in men or >470 ms in women 1
- Check serum electrolytes (potassium, magnesium, calcium) and correct any abnormalities before initiating therapy 1
- Review all concurrent medications for additional QTc-prolonging agents 1
- Assess cardiac history including arrhythmias, heart failure, or structural heart disease 4
If Combination is Unavoidable:
- Use the lowest effective doses of both medications 1
- Perform ECG monitoring at baseline, after 1 week, and then monthly during chronic therapy 1
- Monitor for symptoms of excessive beta-blockade: dizziness, fatigue, syncope, or bradycardia 4
- Consider cardiology consultation for high-risk patients 4
Safer Alternatives
Instead of Domperidone:
- Consider prucalopride (selective 5-HT4 agonist) which does not affect QT interval and has no significant cardiac risks 1
- Erythromycin or azithromycin may be options for small bowel dysmotility, though subject to tachyphylaxis 1
Instead of Propranolol:
- If beta-blockade is needed for tremor or anxiety, consider whether the indication truly requires propranolol or if non-pharmacological approaches could suffice 2
- For cardiac indications, cardioselective beta-blockers like metoprolol may have slightly different risk profiles, though caution remains warranted 5, 6
Critical Pitfalls to Avoid
- Never assume domperidone is safe for long-term use without ECG monitoring - this is a common prescribing error 1
- Do not overlook drug-drug interactions with CYP2D6 inhibitors (certain antidepressants) that can increase propranolol levels and toxicity 7
- Avoid abrupt discontinuation of propranolol after regular use, as rebound symptoms can occur 2, 3
- Remember that propranolol can mask hypoglycemia symptoms in diabetic patients, adding another layer of risk 2, 3