Domperidone — Veterinary Vademecum Drug Reference

Dosage & Administration Guidelines

Species	Route	Dose	Frequency	Duration & Clinical Notes
Dog	PO	0.5-2 mg/kg	q12-24h	Duration: As needed for nausea; for prokinetic, 2-4 weeks Notes: Administer 30 minutes before meals for prokinetic effect.
Cat	PO	0.5-1 mg/kg	q12-24h	Duration: As needed for nausea; for prokinetic, 2-4 weeks Notes: Use with caution in cats due to potential for extrapyramidal effects.
Horse	PO	1.1 mg/kg (for agalactia)	q24h	Duration: Until lactation is established (usually 3-5 days) Notes: For fescue toxicosis, administer once daily; may need to continue until foaling.
Horse	PO	0.1-0.2 mg/kg	q12h	Duration: For ileus, 3-7 days Notes: Prokinetic dose; use with caution in horses with colic.
Rabbit	PO	0.5-1 mg/kg	q12h	Duration: Until GI motility improves Notes: Off-label use; monitor for adverse effects.

Clinical Indications & Species Uses

General Indications

Antiemetic
Gastroprokinetic
Prolactin stimulant (in horses)

Dog (Canine)

Antiemetic for motion sickness and chemotherapy-induced nausea
Gastroprokinetic for delayed gastric emptying and gastroparesis
Management of chronic gastritis and gastric stasis

Cat (Feline)

Antiemetic for nausea and vomiting
Gastroprokinetic for gastric motility disorders

Horse (Equine)

Treatment of agalactia in mares (fescue toxicosis)
Gastroprokinetic for ileus and gastric emptying disorders

Rabbit & Small Mammals

Gastroprokinetic for gastrointestinal stasis (off-label)

Pharmacology & Mechanism of Action

Drug Class: Antiemetic, Prokinetic (Gastrointestinal) | Pharmacological Group: Benzimidazole derivative, Dopamine D2 receptor antagonist

Mechanism of Action: Domperidone is a peripheral dopamine D2 receptor antagonist that does not readily cross the blood-brain barrier. It acts primarily on the chemoreceptor trigger zone (CTZ) and the gastrointestinal tract. In the CTZ, it blocks dopamine receptors, thereby preventing nausea and vomiting. In the gut, it enhances gastrointestinal motility by increasing lower esophageal sphincter tone, improving gastric emptying, and coordinating antral and duodenal contractions. It also stimulates prolactin release from the pituitary, which is useful in treating agalactia in mares.

Pharmacodynamics: Domperidone exerts its antiemetic and prokinetic effects by antagonizing dopamine D2 receptors in the CTZ and the GI tract. It increases gastric motility and accelerates gastric emptying without affecting gastric acid secretion. It also has a mild central antiemetic effect at higher doses. In horses, it stimulates prolactin secretion, which is essential for lactation. The drug has a high affinity for peripheral dopamine receptors and low affinity for central receptors, reducing the risk of extrapyramidal side effects.

⚡ Pharmacokinetics Summary

Absorption: Domperidone is well absorbed after oral administration, but its bioavailability is low (approximately 15-20%) due to extensive first-pass metabolism. Absorption is enhanced when taken with food. In horses, oral absorption is variable; peak plasma concentrations occur within 1-2 hours.

Distribution: Domperidone is widely distributed in tissues, with high concentrations in the GI tract and liver. It has a low volume of distribution (about 1.5 L/kg). It crosses the blood-brain barrier poorly, but it does cross the placenta and is excreted in milk.

Metabolism: Domperidone is extensively metabolized in the liver via oxidative N-dealkylation and hydroxylation, primarily by CYP3A4. The major metabolites are inactive.

Excretion: Domperidone is excreted mainly in the feces (66%) and urine (31%). The elimination half-life is approximately 7-9 hours in humans, but in dogs it is about 2-3 hours, and in horses it is about 4-6 hours.

Half-Life: Dogs: 2-3 hours; Horses: 4-6 hours; Cats: 1-2 hours (estimated)

Bioavailability: Oral bioavailability is low (15-20%) due to first-pass metabolism; in horses, it is about 15%.

Protein Binding: Domperidone is approximately 92-93% bound to plasma proteins.

Available Formulations & Strengths

Oral Tablet 10 mg, 20 mg (PO)

Oral Suspension 1 mg/mL (PO)

Injectable Solution 5 mg/mL (IV, IM)

Contraindications & Clinical Warnings

Contraindications:

Hypersensitivity to domperidone
Gastrointestinal hemorrhage or obstruction
Prolactinoma (pituitary tumor)
Severe hepatic impairment
Concurrent use with strong CYP3A4 inhibitors (e.g., ketoconazole, erythromycin) due to risk of QT prolongation

Warnings & Clinical Precautions:

Use with caution in patients with cardiac disease, especially those with QT prolongation or arrhythmias.
May cause extrapyramidal signs in young animals or those with compromised blood-brain barrier.
In lactating animals, domperidone may increase milk production; monitor for galactagogue effects.
Not approved for use in food animals in many countries; withdrawal times must be observed.
Use with caution in animals with hepatic or renal impairment.
In horses, use with caution in mares with a history of colic or GI obstruction.

Adverse Effects & Reactions

Common:

Increased prolactin levels (galactorrhea)
Dry mouth
Diarrhea
Abdominal cramps

Serious / Severe:

Cardiac arrhythmias (QT prolongation, ventricular arrhythmias)
Extrapyramidal effects (tremors, rigidity)
Seizures (rare)
Hyperprolactinemia leading to gynecomastia or lactation

Rare:

Allergic reactions
Hepatotoxicity
Neuroleptic malignant syndrome (very rare)

Key Drug Interactions

Interacting Drug / Class	Clinical Effect & Mechanism	Severity
CYP3A4 inhibitors (ketoconazole, itraconazole, erythromycin, clarithromycin)	Increased domperidone plasma levels, risk of QT prolongation and cardiac arrhythmias.	High
Anticholinergics (atropine)	May antagonize the prokinetic effects of domperidone.	Moderate
Opioids	May increase the risk of CNS depression and constipation.	Moderate
Metoclopramide	Additive prokinetic effects but increased risk of extrapyramidal side effects.	Moderate
Digoxin	Domperidone may reduce the absorption of digoxin.	Mild

Overdose & Toxicity Management

Signs of Toxicity:

Nausea
Vomiting
Diarrhea
Drowsiness
Extrapyramidal reactions (tremors, rigidity)
Cardiac arrhythmias (QT prolongation, ventricular tachycardia)

Emergency Treatment Protocol: Treatment is symptomatic and supportive. Induce vomiting if recent ingestion and animal is conscious. Administer activated charcoal to reduce absorption. Monitor cardiac function with ECG and treat arrhythmias with appropriate antiarrhythmics (e.g., lidocaine for ventricular arrhythmias). For extrapyramidal signs, administer diphenhydramine or benztropine. Provide fluid therapy and supportive care.

Food Animal Withdrawal Times

🥩 Meat: 7 days🥛 Milk: 3 days

Withdrawal times are not established for all species; consult local regulations. In horses, not for use in animals intended for human consumption. In cattle, off-label use requires extended withdrawal periods.

Storage, Handling & Regulatory Information

Storage Temperature: Store at room temperature (20-25°C) in a tight, light-resistant container.

Light Sensitivity: Light-sensitive — protect from direct exposure.

Handling & Special Conditions: Protect from moisture and light. Keep out of reach of children and animals.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Not FDA-approved for veterinary use; human drug used off-label in animals.

Extra-Label (Off-Label) Use: In the US, domperidone is not FDA-approved for veterinary use; it may be used under AMDUCA for extralabel use in animals. In horses, it is commonly used for agalactia, but it is not approved for food animals. In the EU, it is not approved for food-producing animals.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Domperidone is a valuable antiemetic and prokinetic agent in veterinary medicine, particularly for dogs and cats with gastrointestinal motility disorders. It is also the drug of choice for treating agalactia in mares due to fescue toxicosis. Because it does not cross the blood-brain barrier readily, it has fewer central nervous system side effects compared to metoclopramide. However, it can cause cardiac arrhythmias, especially when used with CYP3A4 inhibitors. In horses, it is important to monitor for signs of colic and to use it cautiously in animals with GI obstruction. For food animals, withdrawal times must be observed, and its use is often off-label. Always consider the risk-benefit profile and consult current veterinary drug references for the latest dosing and safety information.

References & Literature

📚 Plumb's Veterinary Drug Handbook
📚 Papich Veterinary Pharmacology and Therapeutics
📚 Compendium of Veterinary Products (CVP)