What is the role of Domperidone (prokinetic agent) in treating gastrointestinal motility disorders?

Role of Domperidone in Treating Gastrointestinal Motility Disorders

Domperidone should be used with caution as a second-line prokinetic agent for gastrointestinal motility disorders, with mandatory QTc monitoring for long-term use due to significant cardiac safety concerns. 1

Mechanism of Action and Indications

Domperidone is a selective peripheral D2 dopamine receptor antagonist that:

• Stimulates gastric emptying and small intestinal transit
• Enhances the strength of esophageal sphincter contraction
• Does not easily cross the blood-brain barrier, unlike metoclopramide 1, 2
• Acts as a prokinetic agent that stimulates gut motility 3

Primary indications include:

• Early satiety and gastroparesis
• Upper gastrointestinal tract motility disorders
• Nausea and vomiting 1, 4

Efficacy in Clinical Practice

Domperidone has demonstrated efficacy for:

• Improving symptoms of functional dyspepsia 2
• Managing gastroparesis 4
• Treating upper gastrointestinal motility disorders 2
• Controlling nausea and vomiting 1

However, its efficacy appears more pronounced in the proximal gastrointestinal tract, with limited effect on colonic motility disorders 5.

Safety Concerns and Monitoring

Cardiac Safety

• National Patient Safety Agency alerts highlight problems with prolonged QTc interval 1
• Long-term use requires mandatory QTc monitoring 1
• Risk of QT prolongation and torsade de pointes tachycardia exists, particularly with:
  • Intravenous administration
  • Doses >30 mg/day
  • Age >60 years 6
  • Concomitant medications that inhibit CYP3A4 3

Other Safety Considerations

• Hyperprolactinemia can occur due to D2 receptor blockade in the pituitary (outside blood-brain barrier) 2
• Should not be used in patients with suspected or confirmed gastrointestinal blockage 3
• Drug interactions: Significant inhibition of domperidone metabolism may occur with erythromycin and ketoconazole, potentially resulting in much higher domperidone exposure 3

Treatment Algorithm for Gastrointestinal Motility Disorders

1. First-line approaches:

   • Identify and treat underlying conditions (diabetes, connective tissue disorders, electrolyte abnormalities) 1
   • Consider newer prokinetic agents with better safety profiles:
     • Prucalopride (5HT4 receptor agonist) for constipation 1
     • Erythromycin or azithromycin (motilin agonists) for impaired antroduodenal migrating complexes 1

2. When to consider domperidone:

   • After ruling out constipation 1
   • When other prokinetics have failed or are contraindicated
   • Particularly for upper GI motility disorders rather than colonic disorders 5
   • For early satiety and gastroparesis 1

3. Domperidone administration:

   • Use lowest effective dose (typically <30 mg/day) 6
   • Perform baseline ECG to assess QTc interval
   • Regular QTc monitoring for long-term use 1
   • Avoid in patients with:
     • Known cardiac conduction disorders
     • Electrolyte disturbances
     • Concurrent medications that prolong QT interval
     • Suspected or confirmed GI blockage 3

4. Alternative options when domperidone is contraindicated:

   • Erythromycin (900 mg/day) or azithromycin for small bowel dysmotility 1
   • Octreotide (50-100 μg once or twice daily) for refractory cases, especially in systemic sclerosis 1
   • STW5 (Iberogast®) has shown efficacy similar to metoclopramide for functional dyspepsia 1

Special Considerations

In Cancer Patients

• Prokinetic agents like domperidone may help with early satiety after diagnosing and treating constipation 1
• Particularly useful in managing symptoms in patients with advanced cancer 1, 7

In Parkinson's Disease

• Considered first-choice for treating gastrointestinal symptoms in Parkinson's disease patients 6
• Preferred over centrally acting antidopaminergics like metoclopramide due to minimal risk of extrapyramidal effects 6
• However, doses above 30 mg/day should be used with extreme caution due to potential cardiotoxicity 6

When Anticholinergic Medications Cause Constipation

• Consider domperidone as a prokinetic agent to counteract decreased gastrointestinal motility caused by anticholinergic medications 7
• Monitor for potential drug interactions, as many medications have anticholinergic properties 7