Chlorpromazine Hydrochloride — Veterinary Vademecum Drug Reference

Dosage & Administration Guidelines

Species	Route	Dose	Frequency	Duration & Clinical Notes
Dog	PO	0.5-2 mg/kg	q8-12h	Duration: As needed for sedation or antiemesis; usually short-term Notes: For preanesthetic: 0.5-1 mg/kg IM or IV 30-60 minutes before anesthesia. For antiemesis: 0.5-1 mg/kg PO q8h.
Dog	IM	0.5-1 mg/kg	q8-12h	Duration: As needed Notes: IM administration may cause pain at injection site; use deep IM.
Dog	IV	0.5-1 mg/kg	q8-12h	Duration: As needed Notes: Administer slowly; monitor for hypotension.
Cat	PO	0.5-1 mg/kg	q12-24h	Duration: As needed Notes: Cats may be more sensitive to extrapyramidal effects; use lowest effective dose.
Cat	IM	0.5-1 mg/kg	q12-24h	Duration: As needed Notes: For preanesthetic: 0.5 mg/kg IM 30-60 minutes before anesthesia.
Horse	IV	0.2-0.5 mg/kg	q6-12h	Duration: As needed Notes: Use with caution; may cause severe hypotension and penile prolapse. Not commonly used; acepromazine preferred.
Horse	IM	0.5-1 mg/kg	q6-12h	Duration: As needed Notes: IM administration may cause muscle irritation.
Cattle	IM	0.5-1 mg/kg	q12h	Duration: As needed Notes: For sedation; observe withdrawal times.
Cattle	IV	0.2-0.5 mg/kg	q12h	Duration: As needed Notes: Administer slowly; monitor for hypotension.
Small Ruminants	IM	0.5-1 mg/kg	q12h	Duration: As needed Notes: Use with caution; may cause hypothermia.
Rabbit	IM	1-2 mg/kg	q8-12h	Duration: As needed Notes: Not commonly used; safer alternatives (e.g., midazolam) are preferred.
Bird (exotic)	IM	0.5-1 mg/kg	q8-12h	Duration: As needed Notes: Use with caution; may cause respiratory depression.

Clinical Indications & Species Uses

General Indications

Sedation and tranquilization
Antiemesis
Preanesthetic medication
Adjunct in treatment of behavioral disorders

Dog (Canine)

Sedation and tranquilization
Antiemetic (e.g., motion sickness, chemotherapy-induced vomiting)
Preanesthetic medication
Treatment of behavioral disorders (e.g., anxiety, aggression) as adjunctive therapy
Control of intractable hiccups

Cat (Feline)

Sedation and tranquilization
Antiemetic (e.g., motion sickness, chemotherapy-induced vomiting)
Preanesthetic medication
Treatment of behavioral disorders (e.g., anxiety, aggression) as adjunctive therapy

Horse (Equine)

Sedation and tranquilization (especially for handling and minor procedures)
Preanesthetic medication
Treatment of acute laminitis (as a vasodilator, though not first-line)

Cattle (Bovine)

Sedation and tranquilization
Preanesthetic medication
Antiemetic (rarely used)
Treatment of tetanus (as an adjunct to muscle relaxation)

Small Ruminants (Sheep / Goat)

Sedation and tranquilization
Preanesthetic medication

Rabbit & Small Mammals

Sedation and tranquilization (occasionally used, but safer alternatives exist)

Pharmacology & Mechanism of Action

Drug Class: Typical antipsychotic (phenothiazine derivative) | Pharmacological Group: Dopamine receptor antagonist; also blocks alpha-adrenergic, histaminergic, and cholinergic receptors

Mechanism of Action: Chlorpromazine is a phenothiazine neuroleptic that acts primarily by blocking dopamine D2 receptors in the central nervous system, particularly in the mesolimbic and mesocortical pathways, leading to antipsychotic and antiemetic effects. It also antagonizes alpha-1 adrenergic receptors causing hypotension and sedation, H1 histamine receptors contributing to sedation, and muscarinic cholinergic receptors producing anticholinergic effects. In the chemoreceptor trigger zone, it inhibits dopamine and muscarinic receptors, providing antiemetic activity. Additionally, it has local anesthetic and antispasmodic properties.

Pharmacodynamics: Chlorpromazine produces dose-dependent sedation, tranquilization, and reduction in spontaneous activity. It lowers blood pressure via alpha-adrenergic blockade and can cause reflex tachycardia. It has antiemetic effects, lowers body temperature in hypothermic environments, and may cause extrapyramidal signs due to dopamine blockade. In animals, it can potentiate the effects of anesthetics and analgesics. It also has weak anticholinergic and antihistaminic effects.

⚡ Pharmacokinetics Summary

Absorption: Chlorpromazine is well absorbed after oral administration, but undergoes extensive first-pass metabolism in the liver, reducing systemic bioavailability. Peak plasma concentrations occur within 2-3 hours after oral dosing. After IM injection, absorption is more reliable and rapid, with peak levels in 1-2 hours.

Distribution: It is highly lipophilic, widely distributed throughout the body, and crosses the blood-brain barrier. It also crosses the placenta and is excreted in milk. Volume of distribution is large, and it accumulates in tissues such as brain, lung, and liver.

Metabolism: Extensively metabolized in the liver via oxidation, hydroxylation, demethylation, and conjugation. Many metabolites are pharmacologically active. Hepatic metabolism is subject to significant inter-individual variation.

Excretion: Metabolites are excreted primarily in urine (about 70%) and feces (about 30%). A small amount of the parent drug is excreted unchanged. Enterohepatic recirculation may occur.

Half-Life: Dog: approximately 6-12 hours; Cat: approximately 4-8 hours; Horse: approximately 2-4 hours; Cattle: approximately 3-6 hours (estimated).

Bioavailability: Oral bioavailability is low and variable (approximately 25-35%) due to first-pass metabolism; IM bioavailability is nearly complete.

Protein Binding: Approximately 90-95% bound to plasma proteins.

Available Formulations & Strengths

Oral Tablet 10 mg, 25 mg, 50 mg, 100 mg (PO)

Oral Solution (Concentrate) 30 mg/mL, 100 mg/mL (PO)

Injectable Solution 25 mg/mL (IM, IV)

Contraindications & Clinical Warnings

Contraindications:

Known hypersensitivity to phenothiazines
Severe central nervous system depression or comatose states
Patients with bone marrow suppression or blood dyscrasias
Patients with severe cardiovascular disease or hypotension
Patients with pheochromocytoma
Use in animals with a history of seizures (may lower seizure threshold)
Concurrent use with other CNS depressants (e.g., barbiturates, opioids) without dose adjustment

Warnings & Clinical Precautions:

Use with caution in animals with hepatic or renal impairment.
May cause hypotension, especially after IV administration; monitor blood pressure.
Phenothiazines can cause extrapyramidal signs (e.g., tremors, rigidity) in some animals, particularly cats.
May cause photosensitivity; avoid excessive sun exposure after administration.
Use with caution in animals with glaucoma or urinary retention due to anticholinergic effects.
In horses, may cause penile prolapse and paralysis; avoid in breeding stallions.
In food animals, observe withdrawal times.
May cause hypothermia in cold environments; provide appropriate temperature support.
Use with caution in debilitated or geriatric animals.
May cause paradoxical excitement in some animals.

Adverse Effects & Reactions

Common:

Sedation
Hypotension
Tachycardia
Dry mouth
Constipation
Urinary retention
Mydriasis
Decreased body temperature

Serious / Severe:

Extrapyramidal signs (tremors, rigidity, dyskinesia)
Seizures (especially in animals with a history of epilepsy)
Severe hypotension or cardiovascular collapse
Neuroleptic malignant syndrome (rare but potentially fatal)
Blood dyscrasias (e.g., agranulocytosis, leukopenia)
Hepatotoxicity
Prolonged QT interval and arrhythmias

Rare:

Allergic reactions (e.g., skin rash, anaphylaxis)
Cholestatic jaundice
Photosensitivity
Retinopathy (with chronic high-dose use)
Penile prolapse in horses
Feline dysphoria or aggression

Key Drug Interactions

Interacting Drug / Class	Clinical Effect & Mechanism	Severity
CNS depressants (e.g., barbiturates, opioids, anesthetics)	Additive CNS depression and respiratory depression; reduce doses of both agents.	High
Anticholinergic drugs (e.g., atropine)	Additive anticholinergic effects (e.g., dry mouth, constipation, urinary retention).	Moderate
Epinephrine	Paradoxical hypotension due to alpha-adrenergic blockade; avoid concurrent use.	High
Antihypertensive agents	Additive hypotensive effects.	Moderate
Levodopa	Antagonism of therapeutic effects of levodopa.	Moderate
Metoclopramide	Increased risk of extrapyramidal signs.	Moderate
Propranolol and other beta-blockers	Increased plasma levels of both drugs; risk of hypotension and bradycardia.	Moderate
Antacids containing aluminum or magnesium	Reduced absorption of chlorpromazine; separate administration by at least 2 hours.	Mild

Overdose & Toxicity Management

Signs of Toxicity:

Severe CNS depression (lethargy, coma)
Hypotension
Tachycardia or arrhythmias
Hypothermia
Extrapyramidal signs (tremors, rigidity)
Seizures
Respiratory depression
Mydriasis

Emergency Treatment Protocol: Treatment is primarily symptomatic and supportive. Induce emesis if recent oral ingestion and animal is conscious (do not induce in comatose animals). Administer activated charcoal to reduce absorption. Provide IV fluids to maintain blood pressure. Use vasopressors such as norepinephrine or phenylephrine if severe hypotension (avoid epinephrine). Control seizures with diazepam or barbiturates. Manage extrapyramidal signs with diphenhydramine or benztropine. Monitor body temperature and provide warming if hypothermic. In severe cases, consider cardiac monitoring and supportive care in an intensive care setting.

Food Animal Withdrawal Times

🥩 Meat: 7 days🥛 Milk: 3 days

Withdrawal times are not officially established for chlorpromazine in food animals in many countries; consult local regulations. The values provided are conservative estimates based on pharmacokinetic data. In the US, chlorpromazine is not approved for use in food animals; extra-label use requires extended withdrawal periods (e.g., 30 days for meat and 7 days for milk) as per AMDUCA.

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: Protect from moisture. Injectable solutions should be protected from light and freezing. Discard any discolored solutions.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Not FDA-approved for veterinary use; approved for human use. Some formulations may be available as generic.

Extra-Label (Off-Label) Use: In the US, chlorpromazine is not FDA-approved for veterinary species; use in animals is extra-label. Under AMDUCA, extra-label use is permitted only by or on the order of a veterinarian within a valid veterinarian-client-patient relationship, and only when no approved animal drug is available. For food animals, extended withdrawal times must be observed to ensure food safety.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Chlorpromazine is a typical antipsychotic with potent sedative and antiemetic properties. In veterinary medicine, it is used less frequently than other phenothiazines (e.g., acepromazine) due to its more pronounced hypotensive and anticholinergic effects. It can be useful for sedation in aggressive or anxious animals, as a preanesthetic, and for controlling vomiting. However, it should be used with caution in animals with cardiovascular disease, seizure disorders, or hepatic impairment. The drug has a narrow margin of safety and can cause significant adverse effects, especially in cats and horses. In horses, acepromazine is generally preferred because chlorpromazine has a higher risk of penile prolapse and hypotension. For food animals, extra-label use requires careful attention to withdrawal times. Overall, chlorpromazine should be reserved for cases where safer alternatives are unavailable or ineffective.

References & Literature

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