Domperidone
Domperidone is a peripherally acting **dopamine-2 (D2) receptor antagonist** utilized primarily as a gastrointestinal prokinetic and antiemetic agent, as well as a prolactin-release stimulant. Key clinical applications include: - **Horses**: Prevention and treatment of tall fescue toxicosis in periparturient mares, stimulation of lactation (agalactia), and as a diagnostic agent for Equine Pituitary Pars Intermedia Dysfunction (PPID / Equine Cushing's). - **Small Animals**: Used off-label as a prokinetic and antiemetic, particularly for conditions involving delayed gastric emptying. **Clinical Pearl**: Unlike metoclopramide, domperidone does not readily cross the blood-brain barrier. This significantly reduces the risk of central nervous system (CNS) side effects, such as extrapyramidal signs (tremors, twitching), making it an attractive alternative for patients sensitive to centrally acting prokinetics.
Mechanism: Domperidone exerts its effects through multiple pathways: - **Dopamine-2 (D2) Receptor Antagonism** in the GI tract โ enhances gastric motility and accelerates gastric emptying (prokinetic effect). - **D2 Receptor Antagonism** in the **Chemoreceptor Trigger Zone (CRTZ)** โ blocks emetic signaling (antiemetic effect). Because the CRTZ lacks a complete blood-brain barrier, domperidone can act here without entering the deeper CNS. - **Alpha-2 and Beta-2 Adrenergic Receptor Antagonism** โ provides additional modulatory effects on stomach motility. - **Pituitary Gland Disinhibition** โ Dopamine normally inhibits prolactin release. By blocking dopamine receptors, domperidone โ increases **prolactin** secretion โ stimulates milk production (galactagogue effect). This directly counteracts the dopamine-mimetic alkaloids found in toxic tall fescue.
Dosing by species
- As a prokinetic agent ยท 0.05-0.1 mg/kg PO once or twice a day ยท PO ยท q12-24h ยท Scant clinical experience; suggested dose based upon experimental data.
- Antiemetic / Prokinetic ยท 0.1 - 0.5 mg/kg ยท PO ยท q8h-q12h ยท As needed ยท Administer 15-30 minutes before feeding.
- For fescue toxicity ยท 1.1 mg/kg PO once daily starting 10 to 15 days prior to Expected Foaling Date (EFD) ยท PO ยท q24h ยท Up to 5 days after foaling if inadequate milk ยท Treatment may be continued for up to 5 days after foaling if mares are not producing adequate milk.
- As a prokinetic agent ยท 0.05-0.1 mg/kg PO once or twice a day ยท PO ยท q12-24h ยท Scant clinical experience; suggested dose based upon experimental data.
- For vomiting due to gastritis ยท 2-5 mg (total dose) PO two to three times a day ยท PO ยท q8-12h
- Antiemetic / Prokinetic ยท 0.1 - 0.5 mg/kg ยท PO ยท q8h-q12h ยท As needed ยท Administer 15-30 minutes before feeding.
- Leishmaniasis (Treatment and Prevention) ยท 0.5 mg/kg ยท PO ยท sid ยท 28 days ยท For prevention, the 28-day course can be repeated every 3-4 months depending on infection risk.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Routes of administration
Contraindications
- Known hypersensitivity to domperidone
- Presence or suspicion of gastrointestinal obstruction, perforation, or hemorrhage
- Pregnant mares >15 days prior to expected foaling date (unless specifically managed)
- Horses intended for human consumption
- Gastrointestinal hemorrhage
- Mechanical GI obstruction or perforation
- Prolactin-secreting pituitary tumors (prolactinomas)
- Known hypersensitivity to the drug
Adverse effects
- Galactorrhea (inappropriate milk production)
- Gynecomastia
- Premature lactation in horses (dripping milk prior to foaling)
- Failure of passive transfer in foals
- Rarely: somnolence or dystonic reactions
- Arrhythmias (associated with withdrawn injectable human products, especially with hypokalemia or heart disease)
- Galactorrhea (milk production in females)
- Mammary gland hyperplasia
- Changes in estrus cycle
- Mild gastrointestinal upset
Drug interactions
- Azole Antifungals (e.g., ketoconazole) ยท May increase domperidone levels due to metabolic inhibition.
- Anticholinergic Drugs ยท May reduce the gastrointestinal prokinetic efficacy of domperidone.
- Bromocriptine / Cabergoline ยท Domperidone may antagonize their dopamine-agonist effects on prolactin.
- Macrolide Antibiotics (e.g., erythromycin, clarithromycin) ยท May increase domperidone levels.
- Opioids ยท May reduce the gastrointestinal prokinetic efficacy of domperidone. ยท moderate
- Sustained-Release or Enteric-Coated Oral Medications ยท Domperidone may alter the absorptive characteristics of these drugs by decreasing GI transit times.
- Antacids ยท May decrease the oral absorption of domperidone ยท minor
- H2-receptor antagonists (e.g., famotidine) ยท May decrease the oral absorption of domperidone due to altered gastric pH ยท minor
- Ketoconazole ยท Inhibits CYP3A4 metabolism of domperidone, potentially increasing plasma concentrations and risk of QT prolongation ยท major
- Erythromycin ยท Inhibits CYP3A4 metabolism of domperidone, increasing plasma concentrations. ยท major
- Anticholinergics (e.g., Atropine) ยท May antagonize the gastrokinetic effects of domperidone. ยท moderate
Monitoring
- Clinical efficacy (resolution of vomiting, improved gastric emptying, or adequate milk production)
- Serum IgG concentrations in foals born to treated mares
- Serum prolactin levels (if indicated)
- Resolution of nausea and vomiting
- Improvement in clinical signs of Leishmaniasis (if used for this indication)
- Signs of galactorrhea, mammary enlargement, or false pregnancy in females
Overdose
There is no specific antidote for a domperidone overdose. - Employ standard gastrointestinal decontamination procedures if ingestion is recent and the patient is asymptomatic. - Provide supportive and symptomatic care as needed. Monitor for potential neurological signs (especially in MDR1-mutant dogs) or gastrointestinal upset.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturerโs current label.