What medications are used to treat gastroparesis?

Medications for Gastroparesis Treatment

Metoclopramide is the only FDA-approved medication for gastroparesis and should be used as first-line therapy at a dose of 10 mg orally three to four times daily, 30 minutes before meals and at bedtime. 1

First-Line Treatment Approach

Dietary Modifications

• Small, frequent meals (4-6 per day)
• Low-fat, low-fiber diet
• More liquid calories than solid food
• Foods with small particle size to improve gastric emptying

Prokinetic Medications

1. Metoclopramide

   • Dosing: 5-10 mg PO three to four times daily, 30 minutes before meals and at bedtime
   • Only FDA-approved medication specifically for gastroparesis
   • Mechanism: Dopamine receptor antagonist with prokinetic properties
   • Important safety concern: Limited to 12 weeks of use due to risk of tardive dyskinesia (FDA black box warning)
   • Most effective for nausea, vomiting, fullness, and early satiety 2

2. Erythromycin

   • Dosing: 40-250 mg orally three times daily
   • Mechanism: Motilin receptor agonist that stimulates gastric emptying
   • Limitations: Tachyphylaxis (diminishing response over time)
   • Only effective for short-term use 3

Second-Line Options for Refractory Gastroparesis

Alternative Prokinetic

• Domperidone
  • Not FDA-approved in the US (available via investigational drug protocol)
  • Dosing: 10-20 mg three times daily
  • Caution: Doses above 10 mg TID not recommended due to QT prolongation risk
  • May be effective in metoclopramide-resistant cases 4

Medications for Symptom Control

For Nausea and Vomiting

• 5-HT3 receptor antagonists:

  • Ondansetron: 4-8 mg twice or three times daily
  • Granisetron: 1 mg twice daily or 3.1 mg patch weekly

• Phenothiazines:

  • Prochlorperazine: 5-10 mg four times daily
  • Chlorpromazine: 10-25 mg three or four times daily

• Other antiemetics:

  • Trimethobenzamide: 300 mg three times daily
  • Scopolamine: 1.5 mg patch every 3 days
  • Meclizine: 12.5-25 mg three times daily

For Abdominal Pain

• Tricyclic antidepressants:

  • Amitriptyline: 25-100 mg/day
  • Nortriptyline: 25-100 mg/day (less sedating)

• SNRI:

  • Duloxetine: 60-120 mg/day

• Anticonvulsants:

  • Gabapentin: >1200 mg/day in divided doses
  • Pregabalin: 100-300 mg/day in divided doses

Treatment Algorithm

1. Initial approach:

   • Start with dietary modifications
   • Add metoclopramide 10 mg three times daily before meals
   • Use antiemetics as needed for breakthrough symptoms

2. If inadequate response after 4 weeks:

   • Consider switching to erythromycin
   • Or pursue domperidone via FDA investigational protocol

3. For refractory symptoms:

   • Consider combination therapy with different medication classes
   • Add pain management if abdominal pain is prominent
   • Consider gastric electrical stimulation for severe cases

Important Considerations

• Medication withdrawal: Discontinue medications that may worsen gastroparesis:

  • Opioids
  • Anticholinergics
  • Tricyclic antidepressants (if used for other conditions)
  • GLP-1 receptor agonists
  • Pramlintide

• For diabetic gastroparesis: Optimize glycemic control, as hyperglycemia can further delay gastric emptying 3

• Monitoring: Assess for extrapyramidal symptoms with metoclopramide (acute dystonic reactions, drug-induced parkinsonism, akathisia, and tardive dyskinesia)

• Pitfalls to avoid:

  • Long-term metoclopramide use beyond 12 weeks increases risk of tardive dyskinesia
  • Chronic oral metoclopramide may result in diminished effectiveness over time 5
  • Failure to rule out mechanical obstruction before initiating treatment
  • Not addressing medication side effects promptly

Remember that symptom improvement may occur even without normalization of gastric emptying, as medications like metoclopramide have both prokinetic and central antiemetic effects 6, 7.