What are the contraindications for Domperidone (antiemetic and prokinetic agent)?

Domperidone Contraindications

Domperidone is contraindicated in patients with gastrointestinal obstruction, QT prolongation, electrolyte abnormalities, and concurrent use of QT-prolonging medications due to significant risk of cardiac arrhythmias and sudden cardiac death. 1, 2, 3

Major Contraindications

• Gastrointestinal obstruction: Domperidone should not be used in patients with suspected or confirmed gastrointestinal blockage due to its prokinetic properties that stimulate gut motility 4

• Cardiac conditions:

  • History of QT prolongation 2, 3
  • History of dangerous cardiac arrhythmias 5
  • Concurrent use of medications that inhibit CYP3A4 (e.g., erythromycin, ketoconazole) which can significantly increase domperidone exposure 4

• Electrolyte abnormalities: Clinically significant electrolyte disturbances that may increase risk of arrhythmias 5, 3

• Hypersensitivity: Patients with hypersensitivity to domperidone should not receive the medication 4

Relative Contraindications and Precautions

• Age > 60 years: Significantly increased risk of ventricular arrhythmia and sudden cardiac death in this population 2, 6

• High doses: Doses exceeding 30 mg/day are associated with increased risk of cardiac adverse events 2, 6

• Pregnancy and lactation: Safety has not been fully established; use only when benefits clearly outweigh risks 4

• Prolactinoma: Due to domperidone's dopamine antagonist properties 5

• Hepatic impairment: May lead to increased drug exposure 4

Cardiac Safety Concerns

• QT prolongation: Domperidone can prolong the QTc interval, particularly at higher doses 5, 3

• Ventricular arrhythmias: Meta-analysis shows a 70% increased risk of ventricular arrhythmia and sudden cardiac death with current domperidone use 6

• Dose-dependent risk: Safety studies indicate that doses >30 mg/day significantly increase cardiac risk 2, 6

• ECG monitoring: Regular QTc monitoring is recommended for patients on long-term therapy 1

Special Populations

• Elderly patients: Should be used with extreme caution due to significantly higher risk of cardiac adverse events 2, 6

• Patients with existing cardiac disease: Higher risk of adverse cardiac outcomes 3

• Diabetic patients with gastroparesis: While domperidone may be effective for gastroparesis symptoms, cardiac risks must be carefully weighed against benefits 1

Drug Interactions

• CYP3A4 inhibitors: Medications such as erythromycin and ketoconazole can significantly increase domperidone levels, increasing cardiac risk 4

• Other QT-prolonging medications: Concurrent use further increases risk of arrhythmias 3

• P-glycoprotein substrates: Potential for drug interactions as domperidone is a P-glycoprotein substrate 4

Monitoring Recommendations

• Baseline ECG: Before initiating therapy to rule out pre-existing QT prolongation 5

• Regular ECG monitoring: Particularly for patients on higher doses or long-term therapy 1

• Electrolyte monitoring: Regular assessment of potassium, magnesium, and calcium levels 5

• Dose limitation: Keep doses as low as effective, generally not exceeding 30 mg/day 2, 6