What are the recommended medications for treating gastroparesis?

Recommended Medications for Gastroparesis

First-Line Pharmacologic Treatment

Metoclopramide 10 mg three times daily before meals (and at bedtime) is the only FDA-approved medication for gastroparesis and should be the initial pharmacologic treatment, used for a minimum of 4 weeks to assess efficacy. 1, 2, 3

• Metoclopramide is indicated specifically for relief of symptoms associated with acute and recurrent diabetic gastric stasis 3
• The drug has demonstrated statistically significant improvement in nausea and postprandial fullness in controlled trials, with better symptom relief than placebo for nausea, vomiting, fullness, early satiety, and meal tolerance 4
• Be aware of the FDA black box warning for tardive dyskinesia, though the actual risk may be lower than previously estimated by regulatory authorities 1, 2
• Therapy duration should not exceed 12 weeks without careful reassessment due to extrapyramidal side effect risks 2, 5
• In severe cases, metoclopramide can be initiated intravenously (10 mg slowly over 1-2 minutes) before transitioning to oral therapy 3

Important Caveat on Metoclopramide Efficacy

• Chronic oral metoclopramide use may result in tachyphylaxis, with loss of gastrokinetic properties after one month of continuous use 6
• This suggests the need for periodic reassessment of treatment efficacy rather than indefinite continuation 6

Second-Line Pharmacologic Options

Erythromycin

• Erythromycin can be administered orally or intravenously for short-term use in gastroparesis 2, 7
• The major limitation is tachyphylaxis, with effectiveness decreasing to approximately one-third after 72 hours of continuous use 5
• The American Gastroenterological Association issued a conditional recommendation for erythromycin use in gastroparesis 7
• Erythromycin carries QTc prolongation risk and should be avoided in patients with baseline QTc concerns 5

Domperidone

• Domperidone is available in Canada, Mexico, and Europe but is not FDA-approved in the United States 2
• The American Gastroenterological Association issued a conditional recommendation against domperidone as first-line therapy 7

Antiemetic Agents for Symptom Control

When nausea and vomiting are the predominant symptoms, antiemetics can be used alongside or instead of prokinetics:

• Phenothiazines (prochlorperazine, trimethobenzamide, promethazine) are appropriate for nausea and vomiting control 2
• Serotonin (5-HT3) receptor antagonists (ondansetron) can be used for refractory nausea 2
• These agents have not been specifically tested in gastroparesis trials but may provide symptomatic relief 8

Pain Management in Gastroparesis

Opioids must be avoided or withdrawn as they directly impair gastrointestinal motility and worsen gastroparesis 1, 9

Alternative pain management options include:

• Tricyclic antidepressants (TCAs): amitriptyline 25-100 mg/day, nortriptyline 25-100 mg/day, desipramine 25-75 mg/day, or imipramine 25-100 mg/day 9
• SNRIs: duloxetine 60-120 mg/day for visceral pain 9
• Anticonvulsants: gabapentin >1200 mg/day or pregabalin 100-300 mg/day 9
• Note that tertiary amine TCAs have more sedating and anticholinergic side effects, particularly problematic in patients ≥65 years 9

Medications to Avoid

Critical pitfall: Failing to recognize and discontinue medications that induce or worsen gastroparesis:

• Opioid analgesics 1, 9
• GLP-1 agonists 1, 2
• These must be withdrawn before labeling gastroparesis as medically refractory 1

Definition of Medically Refractory Gastroparesis

Gastroparesis is considered medically refractory only after:

• Objectively confirmed gastric emptying delay on 4-hour testing 1, 7
• Implementation of dietary adjustments (low-fat, low-fiber, small particle size meals for minimum 4 weeks) 1, 2
• Adequate trial of metoclopramide 10 mg three times daily for at least 4 weeks 1
• Exclusion of medication-induced causes 1

Treatment Algorithm Based on Predominant Symptoms

For nausea/vomiting predominant: Start with metoclopramide or antiemetics (phenothiazines, 5-HT3 antagonists) 1, 2

For pain predominant: Use TCAs, SNRIs, or anticonvulsants while avoiding opioids 9

For refractory cases despite first-line therapy: Consider short-term erythromycin, combination therapy, or procedural interventions 2, 5

Monitoring and Discontinuation Criteria

• Prokinetic therapy should be discontinued after 3 days if ineffective 5
• Metoclopramide should not continue beyond 12 weeks without reassessment 2
• Weekly assessment of symptom response and adverse effects is prudent 2