Does domperidone (antiemetic medication) worsen diarrhea in patients?

Does Domperidone Worsen Diarrhea?

Domperidone can cause diarrhea as a side effect, but it does not typically worsen pre-existing diarrhea in the same way that antimotility agents like loperamide would be contraindicated in inflammatory conditions. The mechanism is fundamentally different—domperidone is a prokinetic agent that accelerates gastric emptying and intestinal motility, which may lead to looser stools or diarrhea as an adverse effect in some patients, rather than worsening an underlying diarrheal illness 1.

Mechanism and Clinical Context

• Domperidone is a peripheral dopamine-2 receptor antagonist that increases gastric emptying and enhances lower esophageal sphincter pressure, affecting overall gastrointestinal motility 2, 3
• Unlike antimotility agents (loperamide) that are contraindicated in inflammatory diarrhea due to risk of toxic megacolon 4, 5, domperidone's prokinetic action does not carry the same pathophysiologic danger of trapping pathogens or toxins 3
• The drug is used primarily for gastroparesis symptoms at doses of 10 mg three times daily, with maximum dosing of 20 mg three to four times daily 2, 1

Incidence of Diarrhea as Side Effect

• In a large single-center cohort of 115 gastroparesis patients treated with domperidone, diarrhea was reported as one of the most common side effects, though the exact percentage was not specified 1
• Only 14 patients (12%) discontinued treatment due to side effects, with the most common being headache, tachycardia/palpitations, and diarrhea 1
• The majority of patients (69 out of 101) experienced overall symptom improvement despite some experiencing diarrhea as a side effect 1

Clinical Management Algorithm

When diarrhea develops in a patient taking domperidone:

• Assess severity using clinical grading (mild, moderate, severe) and evaluate for dehydration 2
• Rule out other causes including infection, dietary changes, or concurrent medications (particularly proton pump inhibitors like esomeprazole, which can also cause diarrhea) before attributing symptoms solely to domperidone 2
• For mild diarrhea: Symptomatic treatment with oral rehydration may suffice without discontinuing domperidone 2
• Monitor elderly patients more closely as they are at higher risk for dehydration complications 2

Key Distinction from Antimotility Agent Contraindications

• Domperidone does not carry the same contraindications as loperamide in the setting of fever, bloody stools, or inflammatory conditions 4, 5
• The concern with antimotility agents is slowing intestinal transit in the presence of invasive pathogens, leading to bacterial proliferation and toxin accumulation 5
• Domperidone's prokinetic action actually accelerates transit, making it mechanistically different from drugs that worsen diarrhea by trapping pathogens 3

Safety Profile

• Domperidone has an excellent long-term safety profile with minimal central nervous system effects because very little crosses the blood-brain barrier 6, 3
• In chronic treatment studies averaging 23.3 months, domperidone significantly reduced gastrointestinal symptoms and hospitalizations in gastroparesis patients 6
• The drug successfully treats gastroparesis symptoms including nausea, vomiting, and postprandial fullness, even when diarrhea occurs as a side effect in some patients 1, 6

Common Pitfall to Avoid

• Do not confuse domperidone-induced diarrhea with contraindications for antimotility agents. Domperidone causing loose stools as a side effect does not mean it "worsens" pre-existing infectious or inflammatory diarrhea in the dangerous way that loperamide would 5, 3
• If a patient develops diarrhea while on domperidone for gastroparesis, the decision to continue or discontinue should be based on severity of the diarrhea versus benefit for gastroparesis symptoms, not on the same criteria used for antimotility agents 2, 1