Prochlorperazine — Veterinary Vademecum Drug Reference

Dosage & Administration Guidelines

Species	Route	Dose	Frequency	Duration & Clinical Notes
Dog	PO	0.5-1 mg/kg	q8h	Duration: As needed for vomiting; not to exceed 5 days Notes: Use with caution in animals with seizure disorders or liver disease.
Dog	IM	0.1-0.5 mg/kg	q8h	Duration: As needed Notes: For acute vomiting; monitor for hypotension.
Cat	PO	0.5-1 mg/kg	q12-24h	Duration: As needed; not to exceed 5 days Notes: Cats may be more sensitive to extrapyramidal effects.
Cat	IM	0.1-0.5 mg/kg	q8h	Duration: As needed Notes: Use with caution in debilitated animals.
Horse	IM	0.1-0.2 mg/kg	q12h	Duration: As needed Notes: Not commonly used; may cause CNS depression.

Clinical Indications & Species Uses

General Indications

Antiemetic for nausea and vomiting
Sedative/tranquilizer

Dog (Canine)

Antiemetic for vomiting due to motion sickness, chemotherapy, uremia, and gastroenteritis
Treatment of nausea associated with vestibular disease
Sedation and tranquilization in anxious or aggressive dogs (less common)

Cat (Feline)

Antiemetic for vomiting due to various causes (e.g., pancreatitis, chemotherapy, renal disease)
Sedation and tranquilization in fractious cats (less common)

Horse (Equine)

Antiemetic (rarely used; horses are not prone to vomiting)

Cattle (Bovine)

Antiemetic (rarely used; ruminants rarely vomit)

Avian & Poultry

Antiemetic (birds can vomit; may be used in some avian species)

Pharmacology & Mechanism of Action

Drug Class: Phenothiazine Antipsychotic | Pharmacological Group: Dopamine (D2) receptor antagonist; antiemetic

Mechanism of Action: Prochlorperazine is a phenothiazine derivative that primarily acts as a dopamine D2 receptor antagonist in the chemoreceptor trigger zone (CTZ) and, to a lesser extent, in the gastrointestinal tract. By blocking dopamine receptors in the CTZ, it inhibits the emetic reflex. It also has weak anticholinergic, antihistaminic, and alpha-adrenergic blocking properties, which contribute to its antiemetic and sedative effects. At higher doses, it can cause extrapyramidal signs due to dopamine blockade in the basal ganglia.

Pharmacodynamics: Prochlorperazine suppresses nausea and vomiting by raising the threshold for CTZ stimulation. It also has sedative and tranquilizing effects due to its action on the central nervous system. It may cause hypotension via alpha-adrenergic blockade and has weak antimuscarinic effects. Its antiemetic potency is greater than that of chlorpromazine, but it has less sedative and hypotensive activity.

⚡ Pharmacokinetics Summary

Absorption: Prochlorperazine is well absorbed after oral administration, but first-pass metabolism in the liver reduces systemic bioavailability. Peak plasma concentrations occur within 1-2 hours after oral dosing. After intramuscular injection, absorption is rapid.

Distribution: The drug is widely distributed throughout the body, including the brain. It crosses the blood-brain barrier and the placenta, and is excreted in milk. It is highly protein-bound (approximately 90-95%).

Metabolism: Extensively metabolized in the liver via oxidation, hydroxylation, and conjugation. The major metabolite is N-desmethylprochlorperazine, which is also pharmacologically active. Hepatic metabolism is subject to significant interindividual variation.

Excretion: Excreted primarily in the urine as metabolites, with a small amount excreted in feces. Only a small fraction is excreted unchanged. Elimination half-life is approximately 3-8 hours in dogs and cats, but may be prolonged in animals with hepatic impairment.

Half-Life: Dogs: 3-8 hours; Cats: 3-6 hours; Horses: 2-4 hours (estimated)

Bioavailability: Oral: 20-30% due to first-pass metabolism; IM: 100%

Protein Binding: 90-95%

Available Formulations & Strengths

Oral Tablet 5 mg, 10 mg, 25 mg (PO)

Oral Solution 5 mg/mL (PO)

Injectable Solution 5 mg/mL (IM/IV)

Suppository 2.5 mg, 5 mg, 25 mg (Rectal)

Contraindications & Clinical Warnings

Contraindications:

Hypersensitivity to phenothiazines
Severe CNS depression or comatose states
Known blood dyscrasias
Pheochromocytoma
Concurrent use with other CNS depressants (relative contraindication)
Use in animals with seizure disorders (may lower seizure threshold)

Warnings & Clinical Precautions:

Use with caution in animals with hepatic or renal disease
May cause hypotension, especially after parenteral administration
May cause extrapyramidal signs (muscle tremors, rigidity, restlessness)
Phenothiazines can cause photosensitivity; avoid excessive sun exposure
Use with caution in debilitated, geriatric, or pediatric animals
May cause sedation; avoid concurrent use with other sedatives
In horses, may cause CNS excitation or disorientation
In food animals, observe withdrawal times

Adverse Effects & Reactions

Common:

Sedation
Hypotension
Dry mouth
Constipation
Urinary retention

Serious / Severe:

Extrapyramidal signs (tremors, rigidity, dyskinesia)
Neuroleptic malignant syndrome (rare)
Blood dyscrasias (leukopenia, agranulocytosis)
Hepatotoxicity
Seizures (in predisposed animals)

Rare:

Allergic reactions
Photosensitivity
Prolonged QT interval
Cholestatic jaundice

Key Drug Interactions

Interacting Drug / Class	Clinical Effect & Mechanism	Severity
CNS depressants (barbiturates, opioids, anesthetics)	Additive sedation and respiratory depression	High
Anticholinergics	Increased anticholinergic effects (dry mouth, constipation, urinary retention)	Moderate
Epinephrine	Paradoxical hypotension due to alpha-adrenergic blockade	High
Metoclopramide	Increased risk of extrapyramidal signs	Moderate
Antihypertensives	Additive hypotensive effects	Moderate
Drugs that prolong QT interval (e.g., fluoroquinolones, macrolides)	Increased risk of cardiac arrhythmias	Moderate

Overdose & Toxicity Management

Signs of Toxicity:

Severe CNS depression
Hypotension
Extrapyramidal signs (tremors, rigidity)
Seizures
Arrhythmias
Respiratory depression
Coma

Emergency Treatment Protocol: Treatment is symptomatic and supportive. Induce emesis (if recent oral ingestion and animal is conscious) or perform gastric lavage. Administer activated charcoal to reduce absorption. Provide IV fluids to support blood pressure. Treat hypotension with norepinephrine or phenylephrine (avoid epinephrine). Control seizures with diazepam or barbiturates. Treat extrapyramidal signs with diphenhydramine or benztropine. Monitor cardiac function and respiratory status. In severe cases, provide mechanical ventilation.

Food Animal Withdrawal Times

🥩 Meat: 7 days🥛 Milk: 3 days

Withdrawal times are not officially established for prochlorperazine in food animals. The values provided are conservative estimates based on the drug's half-life and common practice. Always consult the label or a veterinary pharmacologist for specific guidance.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature (20-25°C, 68-77°F). Protect from light.

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

Handling & Special Conditions: Keep in a tight, light-resistant container. Do not freeze injectable solutions.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Approved for use in dogs and cats for antiemetic and tranquilizing effects. Not approved for food animals.

Extra-Label (Off-Label) Use: In the US, extra-label use of prochlorperazine in food animals is permitted under AMDUCA (Animal Medicinal Drug Use Clarification Act) only with a valid veterinary-client-patient relationship and a written prescription. It is prohibited in lactating dairy cattle if the drug is not approved for that species. Withdrawal times must be extended appropriately.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Prochlorperazine is a useful antiemetic in dogs and cats, particularly for vomiting associated with motion sickness, chemotherapy, and gastroenteritis. However, it is less commonly used than newer antiemetics like maropitant (Cerenia) due to its potential for sedation and extrapyramidal side effects. It should be used with caution in animals with seizure disorders, hepatic disease, or cardiovascular compromise. Parenteral administration may cause hypotension, so blood pressure should be monitored. In cats, extrapyramidal signs may be more pronounced; if they occur, treatment with diphenhydramine (0.5-1 mg/kg IV or IM) may be effective. Prochlorperazine is not recommended for use in rabbits or other species that cannot vomit. In food animals, its use is limited and withdrawal times must be observed. Always consider alternative antiemetics with better safety profiles when available.

References & Literature

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