What are the potential interactions and precautions when using domperidone with other medications?

Domperidone Medication Interactions and Precautions

Domperidone should not be used concurrently with medications that prolong the QT interval due to significant risk of cardiac arrhythmias, including torsade de pointes. 1, 2, 3

Key Cardiac Interaction Concerns

Domperidone has significant potential for QT interval prolongation, which can lead to serious cardiac events:

• QT-prolonging medications to avoid with domperidone:

  • Antineoplastics: cabozantinib, ceritinib, crizotinib, nilotinib, osimertinib, vandetanib, vemurafenib, oxaliplatin, arsenic trioxide 1
  • Antidepressants: (es)citalopram and other serotonin reuptake inhibitors 1, 2
  • Antiemetics: ondansetron (especially doses >8mg) 1
  • Antipsychotics 2
  • Macrolide antibiotics (except azithromycin) 1, 4

• Research findings: 69.7% of patients prescribed domperidone are inappropriately co-prescribed QT-prolonging medications, and 73.3% of non-fatal cardiac events reported to the FDA occurred in patients receiving such combinations 3

Metabolic Pathway Interactions

Domperidone is primarily metabolized through:

• CYP3A4 pathway: Medications that inhibit CYP3A4 can significantly increase domperidone exposure 4

  • Strong inhibitors to avoid: erythromycin, ketoconazole 4
  • These combinations can result in multi-fold increases in domperidone levels 4

• P-glycoprotein substrate: Drugs that inhibit P-glycoprotein can increase domperidone levels 4

Other Important Precautions

• Gastrointestinal blockage: Domperidone is contraindicated in patients with suspected or confirmed gastrointestinal blockage due to its prokinetic effects 4

• Electrolyte disturbances: Avoid combinations that may cause hypokalemia (corticosteroids, cisplatin, medications causing digestive disorders) as this increases risk of torsade de pointes 1

• Bradycardia-inducing medications: Caution with medications like thalidomide that can cause bradycardia, as this increases arrhythmia risk 1

Monitoring Recommendations

When domperidone use is necessary:

1. Baseline ECG: Evaluate QTc interval before starting treatment 2
2. Regular ECG monitoring: Mandatory for long-term use 2
3. Lowest effective dose: Use <30 mg/day when possible 2, 5
4. Age consideration: Extra caution in patients >60 years 5

Alternative Medications

When domperidone is contraindicated due to medication interactions:

• Metoclopramide: Effective alternative, though has higher risk of extrapyramidal side effects 2, 6
• Erythromycin or azithromycin: For small bowel dysmotility (azithromycin has fewer QT concerns) 2
• Prucalopride: For constipation-predominant symptoms 2
• STW5 (Iberogast®): For functional dyspepsia 2

Special Populations

• Parkinson's disease: Domperidone is often used to manage gastrointestinal symptoms in patients taking dopamine agonists, but requires careful cardiac monitoring 5

• Diabetic gastroparesis: While effective at doses of 40-80 mg/day, cardiac risk must be balanced against benefit, especially with concomitant medications 7

The evidence clearly demonstrates that domperidone's cardiac risk is significantly amplified when combined with other QT-prolonging medications, making thorough medication review essential before prescribing.