Trimeprazine Tartrate — Veterinary Vademecum Drug Reference

Dosage & Administration Guidelines

Species	Route	Dose	Frequency	Duration & Clinical Notes
Dog	PO	0.5-2 mg/kg (as trimeprazine tartrate)	q8-12h	Duration: As needed for pruritus; for motion sickness, administer 30-60 minutes before travel Notes: May be used in combination with prednisolone (e.g., Temaril-P) for enhanced antipruritic effect. Adjust dose based on response and sedation.
Cat	PO	0.5-1 mg/kg	q12h	Duration: As needed for pruritus Notes: Cats may be more sensitive to anticholinergic effects; monitor for signs of dry mouth or urinary retention.
Horse	PO	0.5-1 mg/kg	q12h	Duration: As needed for pruritus Notes: Not FDA-approved for horses; use with caution. May cause CNS depression.
Rabbit	PO	0.5-1 mg/kg	q12h	Duration: As needed for pruritus Notes: Off-label use; limited safety data. Monitor for GI stasis due to anticholinergic effects.

Clinical Indications & Species Uses

General Indications

Symptomatic relief of pruritus in allergic skin conditions
Sedation
Antiemetic for motion sickness

Dog (Canine)

Pruritus associated with allergic dermatitis
Urticaria
Motion sickness (as an antiemetic)
Sedation (as a preanesthetic or for behavioral calming)

Cat (Feline)

Pruritus associated with allergic dermatitis
Urticaria
Sedation (as a preanesthetic or for behavioral calming)

Horse (Equine)

Pruritus associated with allergic conditions (e.g., insect hypersensitivity)
Sedation (as a preanesthetic)

Rabbit & Small Mammals

Pruritus (off-label use)
Sedation (off-label use)

Exotic & Other Species

Pruritus (off-label use in small mammals such as guinea pigs, rats)

Pharmacology & Mechanism of Action

Drug Class: Phenothiazine Antihistamine | Pharmacological Group: First-generation antihistamine (H1 receptor antagonist) with sedative and antiemetic properties

Mechanism of Action: Trimeprazine is a phenothiazine derivative that acts primarily as a competitive antagonist at histamine H1 receptors, thereby blocking the effects of histamine in allergic reactions. It also exhibits central nervous system depressant effects due to its antagonism of dopamine, alpha-adrenergic, and muscarinic receptors, leading to sedation, antiemesis, and potential extrapyramidal effects. Its antipruritic action is attributed to both antihistaminic and local anesthetic properties.

Pharmacodynamics: Trimeprazine reduces capillary permeability, wheal-and-flare responses to histamine, and pruritus associated with allergic dermatitis. It also has anticholinergic effects that can cause dry mouth, urinary retention, and constipation. Sedation is a prominent effect, especially at higher doses. It may potentiate the effects of other CNS depressants.

⚡ Pharmacokinetics Summary

Absorption: Well absorbed from the gastrointestinal tract after oral administration. Onset of action typically occurs within 30-60 minutes.

Distribution: Widely distributed throughout the body, crosses the blood-brain barrier, and is distributed into tissues. It crosses the placenta and is excreted in milk.

Metabolism: Extensively metabolized in the liver via oxidation, demethylation, and conjugation. Phenothiazines are metabolized by hepatic microsomal enzymes (CYP450 system).

Excretion: Excreted primarily in urine as metabolites, with small amounts excreted in feces. Biliary excretion may occur.

Half-Life: In dogs, the half-life is approximately 6-12 hours; in cats, it is approximately 4-8 hours. In horses, it is approximately 2-4 hours.

Bioavailability: Oral bioavailability is variable, estimated at 40-60% due to first-pass metabolism.

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

Available Formulations & Strengths

Oral Tablet 5 mg, 10 mg, 25 mg (often combined with prednisolone in products like Temaril-P) (PO)

Oral Syrup 2.5 mg/5 mL (historically available) (PO)

Injectable Solution Not commonly available; may be compounded (IM)

Contraindications & Clinical Warnings

Contraindications:

Hypersensitivity to phenothiazines
Severe CNS depression or comatose states
Concurrent use with other CNS depressants (e.g., barbiturates, opioids) unless carefully monitored
Patients with a history of seizures (may lower seizure threshold)
Patients with glaucoma (anticholinergic effects may increase intraocular pressure)
Patients with prostatic hypertrophy or urinary retention
Patients with severe cardiovascular disease or hypotension
Pregnancy (especially near term) unless benefits outweigh risks; may cause neonatal depression

Warnings & Clinical Precautions:

Use with caution in debilitated or geriatric animals, as they may be more sensitive to sedative and hypotensive effects.
May cause paradoxical excitation in some animals, especially at low doses.
Phenothiazines can cause extrapyramidal signs (e.g., tremors, rigidity) in some animals; discontinue if these occur.
Anticholinergic effects may exacerbate conditions such as dry eye (keratoconjunctivitis sicca), constipation, and urinary retention.
In horses, use with caution due to potential for CNS depression and hypotension; monitor closely.
In food animals, avoid use due to lack of withdrawal times and potential residues.
May interfere with skin testing for allergies; discontinue at least 7 days before testing.
Use with caution in animals with hepatic or renal impairment, as metabolism and excretion may be reduced.

Adverse Effects & Reactions

Common:

Sedation
Lethargy
Dry mouth
Constipation
Urinary retention
Mydriasis (pupil dilation)
Decreased appetite

Serious / Severe:

Severe hypotension
Arrhythmias (e.g., QT prolongation)
Seizures (especially in epileptic animals)
Extrapyramidal signs (tremors, rigidity)
Neuroleptic malignant syndrome (rare but potentially fatal)
Blood dyscrasias (e.g., agranulocytosis, leukopenia)

Rare:

Photosensitivity
Cholestatic jaundice
Skin reactions (e.g., rash, urticaria)
Paradoxical excitation or aggression
Hyperprolactinemia (with chronic use)

Key Drug Interactions

Interacting Drug / Class	Clinical Effect & Mechanism	Severity
CNS depressants (barbiturates, opioids, benzodiazepines, general anesthetics)	Additive CNS depression and respiratory depression; reduce doses of both agents.	High
Anticholinergic drugs (atropine, tricyclic antidepressants)	Additive anticholinergic effects (dry mouth, urinary retention, tachycardia).	Moderate
Epinephrine	Phenothiazines may reverse the pressor effect of epinephrine, leading to severe hypotension.	High
Antihypertensive agents (e.g., beta-blockers, ACE inhibitors)	Additive hypotensive effects.	Moderate
MAO inhibitors (e.g., selegiline)	Increased risk of hypotension and CNS depression.	Moderate
Drugs that prolong QT interval (e.g., fluoroquinolones, macrolides, amiodarone)	Increased risk of ventricular arrhythmias.	High
Phenytoin	May increase phenytoin levels due to CYP inhibition.	Moderate

Overdose & Toxicity Management

Signs of Toxicity:

Severe CNS depression (coma, respiratory depression)
Hypotension
Tachycardia or arrhythmias
Extrapyramidal signs (tremors, rigidity)
Seizures
Hyperthermia or hypothermia
Mydriasis
Dry mucous membranes

Emergency Treatment Protocol: Treatment is symptomatic and supportive. Induce emesis if recent ingestion and animal is conscious (do not induce if CNS depression is severe). Administer activated charcoal to reduce absorption. Provide IV fluids for hypotension; use norepinephrine or phenylephrine for vasopressor support (avoid epinephrine). Control seizures with diazepam or barbiturates. Monitor cardiac function and body temperature. For extrapyramidal signs, diphenhydramine (1-2 mg/kg IV or IM) may be used. In severe cases, consider gastric lavage and respiratory support.

Food Animal Withdrawal Times

Not approved for use in food animals. No withdrawal times established. Do not use in animals intended for human consumption.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature 20-25°C (68-77°F), with excursions permitted between 15-30°C (59-86°F).

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

Handling & Special Conditions: Protect from light and moisture. Keep container tightly closed. Do not freeze oral solutions.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Approved for use in dogs and cats in combination with prednisolone (e.g., Temaril-P) for pruritus. Not approved for horses or other species.

Extra-Label (Off-Label) Use: In the US, extra-label use in food animals is prohibited due to lack of withdrawal times and potential residues. In non-food animals, extra-label use is permitted under AMDUCA with appropriate veterinary oversight.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Trimeprazine is a first-generation antihistamine with sedative properties, primarily used for pruritus in dogs and cats, often in combination with corticosteroids (e.g., Temaril-P). It is also used off-label for sedation and motion sickness. Due to its anticholinergic and CNS depressant effects, it should be used with caution in animals with cardiovascular disease, glaucoma, urinary retention, or seizure disorders. It is not recommended for food animals. Clinical monitoring should include assessment of sedation, appetite, and any signs of anticholinergic effects. For allergic pruritus, it may be less effective than newer antihistamines or corticosteroids, but it can be useful as an adjunctive therapy. Always consider the potential for drug interactions, especially with other CNS depressants. In horses, use is limited and should be under close supervision. For small mammals and exotic pets, use is off-label and based on anecdotal evidence; doses should be extrapolated cautiously. Withdrawal times are not established, so avoid in food-producing animals. Store away from light and moisture. Prescription required.

References & Literature

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