What is the role of Itopride (N-[4-[2-(dimethylamino)ethoxy]benzyl]-3,4-dimethoxybenzamide) 50mg in treating gastroparesis?

Role of Itopride 50mg in Gastroparesis

Itopride 50mg three times daily before meals is recommended for gastroparesis, particularly for long-term management when metoclopramide is contraindicated or for anticipated treatment beyond 12 weeks, due to its favorable safety profile with no significant QT interval effects or extrapyramidal side effects. 1

Mechanism of Action and Pharmacology

Itopride has a dual mechanism of action:

• Dopamine D2 receptor antagonist
• Acetylcholinesterase inhibitor

This dual action enhances gastric motility without the significant central nervous system side effects associated with other prokinetics.

Clinical Evidence for Itopride in Gastroparesis

Efficacy

• In diabetic gastroparesis, itopride has shown significant improvement in upper gastrointestinal symptoms with a recommended dose of 150mg daily in divided doses 1, 2
• A prospective study of 988 patients with diabetic gastroparesis demonstrated significant improvement in upper gastrointestinal symptom severity scores after 4 weeks of treatment with itopride SR 150mg once daily 2
• The IPOD trial (743 patients) showed significant improvement in symptoms including nausea, vomiting, early satiety, bloating, postprandial fullness, epigastric pain, and regurgitation with combination therapy of itopride and pantoprazole 3

Safety Profile

• Itopride is generally well-tolerated with no significant effect on QT interval, unlike other prokinetics such as cisapride and domperidone 1
• Minimal extrapyramidal side effects compared to metoclopramide 1
• In a study of 587 patients, only 1.54% experienced adverse events, with most being mild and not requiring discontinuation 4

Treatment Algorithm for Gastroparesis

1. First-line therapy:

   • Metoclopramide 5-10mg orally four times daily, 30 minutes before meals and at bedtime 5, 1
   • Limited to ≤12 weeks due to FDA black box warning for tardive dyskinesia risk

2. When to consider itopride:

   • For anticipated long-term treatment beyond 12 weeks 1
   • When metoclopramide is contraindicated or not tolerated 1
   • In patients at higher risk for tardive dyskinesia (elderly) 1
   • When QT prolongation is a concern (itopride has minimal effect on QT interval) 1

3. Dosing of itopride:

   • Standard dose: 50mg three times daily before meals 1, 4
   • For diabetic gastroparesis: 150mg daily in divided doses 1, 2
   • Extended-release formulation (SR): 150mg once daily 2

Combination Therapy

• Itopride can be used in combination with other agents for enhanced efficacy:
  • With PPIs for gastroparesis with concurrent GERD symptoms 3
  • In critically ill patients, combination with metoclopramide may provide synergistic effects 6

Additional Benefits of Itopride

• Improves lower esophageal sphincter function by inhibiting transient LES relaxations, which may benefit patients with concurrent GERD 7
• May be particularly effective for functional dyspepsia symptoms that overlap with gastroparesis 4

Important Monitoring and Precautions

• Monitor for improvement in gastroparesis symptoms (nausea, vomiting, early satiety, bloating)
• In diabetic patients, optimize glycemic control as hyperglycemia can further delay gastric emptying 1
• Unlike metoclopramide, routine monitoring for extrapyramidal symptoms is less critical with itopride
• Unlike domperidone, routine ECG monitoring for QT prolongation is not essential with itopride

Limitations and Considerations

• Itopride is not FDA-approved in the United States specifically for gastroparesis
• Most robust evidence comes from studies in Asian populations
• Consider individual patient factors including comorbidities, concurrent medications, and symptom profile when selecting prokinetic therapy