What are the potential side effects of domperidone, particularly in patients with a history of heart conditions or those taking other medications that can affect heart rhythm?

Side Effects of Domperidone

Domperidone carries a significant 70% increased risk of ventricular arrhythmia and sudden cardiac death, particularly in patients over 60 years old or those taking doses above 30 mg/day, making cardiac screening and dose limitation essential before prescribing. 1, 2, 3

Cardiovascular Side Effects (Most Critical)

QT Prolongation and Arrhythmias

• QT interval prolongation is the most serious adverse effect, leading to life-threatening torsades de pointes and ventricular arrhythmias 1, 4, 2
• Meta-analysis demonstrates current domperidone use increases the risk of ventricular arrhythmia and sudden cardiac death with a pooled adjusted odds ratio of 1.70 (95% CI: 1.47-1.97) 2, 3
• Risk is particularly elevated with doses exceeding 30 mg/day 1, 5, 6
• The intravenous formulation was withdrawn from markets in the 1980s specifically due to fatal cardiac arrhythmias 7, 8

High-Risk Patient Populations for Cardiac Events

• Patients over 60 years old have substantially higher cardiac complication risk 1, 5, 2
• Those with pre-existing QT prolongation (>440 ms in males, >450 ms in females) 1, 5
• Patients with electrolyte abnormalities (hypokalemia, hypomagnesemia) 1, 5
• Individuals with congestive heart failure, bradycardia, or cardiac hypertrophy 1
• Patients concurrently using CYP3A4 inhibitors or other QT-prolonging medications 1, 4, 5

Gastrointestinal Side Effects

• Nausea and vomiting (paradoxically, despite being an antiemetic) 1
• Constipation 1
• Dry mouth 1

Neurological Side Effects

• Domperidone has significantly fewer extrapyramidal side effects compared to metoclopramide because it does not readily cross the blood-brain barrier 1, 4
• Extrapyramidal effects are rare but can include restlessness and movement disorders 1, 4
• Headache may occur 1

Endocrine Side Effects

• Hyperprolactinemia (due to dopamine D2-receptor antagonism) 1
• Galactorrhea 1
• Gynecomastia 1

Essential Pre-Treatment Cardiac Screening

Before prescribing domperidone, obtain a baseline ECG in patients over 60 years old, those with cardiac risk factors, or anyone who will receive doses over 30 mg/day. 1, 5

Specific Screening Steps:

• Measure baseline QTc interval on ECG 1, 5
• Check serum potassium and magnesium levels 1, 5
• Review all concurrent medications for QT-prolonging drugs 4, 5
• Assess for structural heart disease, congestive heart failure, or bradycardia 1

Safe Dosing to Minimize Cardiac Risk

Start with 10 mg three times daily (maximum 30 mg/day total) to minimize cardiovascular risk while maintaining therapeutic efficacy. 1, 4, 5

Dosing Algorithm:

• Initial dose: 10 mg three times daily before meals 1, 4, 5
• Maximum dose: 20 mg three to four times daily (60-80 mg/day total) only if absolutely necessary 1, 5
• Avoid exceeding 30 mg/day whenever possible due to exponentially increased cardiac risk 1, 5, 6
• Duration of effect is 7-14 hours per dose 1, 4

Absolute Contraindications

Do not prescribe domperidone in patients with:

• Pre-existing QT prolongation (QTc >440 ms males, >450 ms females) 1, 5
• Concurrent use of strong CYP3A4 inhibitors (ketoconazole, erythromycin, clarithromycin) 1, 5
• Electrolyte abnormalities (uncorrected hypokalemia or hypomagnesemia) 1, 5
• Concomitant use of other QT-prolonging medications 4, 5
• Severe hepatic impairment 1

Long-Term Use Restrictions

The British Society of Gastroenterology explicitly states domperidone should no longer be used long-term for chronic gastrointestinal motility disorders due to cumulative cardiac risks. 1

• Limit treatment duration to the shortest effective period 1, 5
• The European Medicines Agency recommends against long-term use due to cumulative cardiac risks 5
• Regular ECG monitoring is warranted for any extended therapy 4, 5

Drug Interactions Increasing Cardiac Risk

Avoid combining domperidone with:

• Other QT-prolonging drugs (antiarrhythmics, certain antibiotics, antipsychotics) 4, 5
• CYP3A4 inhibitors that increase domperidone plasma levels 1, 5
• Medications causing electrolyte depletion (diuretics) 1

Common Clinical Pitfalls to Avoid

• Never ignore cardiac screening, even in younger patients, as QT prolongation risk is real and potentially fatal 4, 2, 3
• Do not exceed 30 mg/day without compelling justification and enhanced cardiac monitoring 1, 5, 6
• Avoid prescribing to elderly patients (>60 years) without careful risk-benefit assessment and ECG monitoring 1, 5, 2
• Do not combine with other QT-prolonging medications without cardiology consultation 4, 5
• Never use domperidone as a first-line agent when safer alternatives exist for the specific indication 1, 4

Monitoring During Treatment

• Periodic ECG monitoring, especially in high-risk patients 4, 5
• Monitor for signs of arrhythmia (palpitations, syncope, dizziness) 1, 4
• Regular assessment of electrolyte levels (potassium, magnesium) 1, 5
• Document patient education regarding cardiac symptoms requiring immediate medical attention 4