Promethazine Hydrochloride — Veterinary Vademecum Drug Reference

Dosage & Administration Guidelines

Species	Route	Dose	Frequency	Duration & Clinical Notes
Dog	PO	0.2-0.5 mg/kg (antihistamine); 1-2 mg/kg (antiemetic/sedative)	q8-12h	Duration: As needed for clinical signs; usually 3-7 days Notes: Start with lower dose for antihistamine effect; higher doses for sedation/antiemesis.
Dog	IM	0.2-0.5 mg/kg	q8-12h	Duration: Short-term use Notes: IM administration may be painful; use deep IM.
Cat	PO	0.2-0.4 mg/kg	q12h	Duration: As needed Notes: Cats may be sensitive to anticholinergic effects; use cautiously.
Horse	IV/IM	0.5-1 mg/kg	q8-12h	Duration: Short-term Notes: IV administration should be slow; may cause excitement in some horses.
Cattle	IM	0.5-1 mg/kg	q12h	Duration: Short-term Notes: Extra-label; observe withdrawal times.

Clinical Indications & Species Uses

General Indications

Symptomatic relief of allergic conditions
Prevention and treatment of motion sickness
Antiemetic
Sedation

Dog (Canine)

Antihistamine for allergic dermatitis, pruritus, urticaria
Antiemetic for motion sickness and chemotherapy-induced nausea
Sedative premedication
Adjunct in anaphylaxis (not primary)

Cat (Feline)

Antihistamine for allergic skin conditions (limited efficacy)
Antiemetic (off-label)
Sedation (off-label)

Horse (Equine)

Antihistamine for allergic reactions, urticaria, pruritus (off-label)
Sedative adjunct (off-label)

Cattle (Bovine)

May be used for allergic reactions (off-label)

Rabbit & Small Mammals

Potential for anticholinergic side effects

Pharmacology & Mechanism of Action

Drug Class: Phenothiazine Antihistamine (H1 receptor antagonist) | Pharmacological Group: Antihistamine, Antiemetic, Sedative

Mechanism of Action: Promethazine is a phenothiazine derivative that acts primarily as a competitive antagonist at histamine H1 receptors, thereby preventing histamine-mediated effects such as vasodilation, increased vascular permeability, and bronchoconstriction. It also exhibits central antiemetic activity by blocking dopamine D2 receptors in the chemoreceptor trigger zone (CTZ) and possibly by anticholinergic effects on the vestibular apparatus. Additionally, it has sedative properties due to antagonism of central histamine and dopamine receptors, and it possesses local anesthetic and antimuscarinic actions.

Pharmacodynamics: Promethazine produces dose-dependent sedation, antihistaminic effects, and antiemesis. It reduces capillary permeability, pruritus, and allergic reactions. Its central effects include sedation, antiemesis, and some anticholinergic effects (dry mouth, urinary retention). It has minimal effect on gastric acid secretion. The duration of action is typically 4-6 hours for antihistamine effects, but sedation may last longer.

⚡ Pharmacokinetics Summary

Absorption: Promethazine is well absorbed after oral, IM, or rectal administration. Peak plasma concentrations occur within 2-3 hours after oral dosing. Food may delay absorption.

Distribution: Widely distributed throughout the body, including the CNS. It crosses the blood-brain barrier and placenta, and is distributed into milk. Volume of distribution is large. Protein binding is approximately 76-93%.

Metabolism: Extensively metabolized in the liver via oxidation, N-demethylation, and sulfoxidation, primarily by CYP2D6 and other cytochrome P450 enzymes. Metabolites are excreted in urine.

Excretion: Excreted primarily in urine as metabolites and unchanged drug (less than 1%). Biliary excretion also occurs. The elimination half-life in dogs is approximately 6-8 hours, but may be prolonged in neonates or with hepatic impairment.

Half-Life: Dogs: 6-8 hours; Cats: approximately 4-6 hours (estimated); Horses: 2-4 hours (estimated); Humans: 10-14 hours.

Bioavailability: Oral bioavailability is approximately 25% due to extensive first-pass metabolism; IM bioavailability is nearly complete.

Protein Binding: 76-93%

Available Formulations & Strengths

Oral Tablet 12.5 mg, 25 mg, 50 mg (PO)

Oral Syrup 6.25 mg/5 mL, 25 mg/5 mL (PO)

Injectable Solution 25 mg/mL, 50 mg/mL (IM/IV)

Suppository 12.5 mg, 25 mg, 50 mg (Rectal)

Contraindications & Clinical Warnings

Contraindications:

Hypersensitivity to promethazine or other phenothiazines
Comatose patients or those with CNS depression
Severe cardiovascular disease (hypotension, arrhythmias)
Concurrent use of MAO inhibitors
Neonates or debilitated animals (risk of respiratory depression)
History of seizures (may lower seizure threshold)

Warnings & Clinical Precautions:

Use with caution in animals with hepatic disease, cardiovascular disease, glaucoma, prostatic hyperplasia, or urinary retention.
May cause paradoxical excitement in some animals, especially cats and horses.
May cause respiratory depression in neonates or animals with respiratory compromise.
Phenothiazines can cause hypotension, especially after IV administration.
Prolonged use may cause extrapyramidal signs.
In food animals, observe withdrawal times; extra-label use requires veterinary oversight.
Avoid perivascular injection as it is irritating.

Adverse Effects & Reactions

Common:

Sedation
Drowsiness
Dry mouth
Constipation
Urinary retention
Mydriasis

Serious / Severe:

Hypotension
Respiratory depression
Arrhythmias
Seizures
Extrapyramidal signs (muscle tremors, rigidity)
Blood dyscrasias (rare)
Neuroleptic malignant syndrome (rare)

Rare:

Photosensitivity
Cholestatic jaundice
Agranulocytosis
Anaphylactoid reactions

Key Drug Interactions

Interacting Drug / Class	Clinical Effect & Mechanism	Severity
CNS depressants (barbiturates, opioids, anesthetics)	Additive sedation and respiratory depression	High
Anticholinergic drugs (atropine, tricyclic antidepressants)	Additive anticholinergic effects (dry mouth, ileus, tachycardia)	Moderate
MAO inhibitors	Increased risk of hypotension and extrapyramidal effects	High
Epinephrine	May cause paradoxical hypotension due to alpha-adrenergic blockade	Moderate
CYP2D6 inhibitors (e.g., fluoxetine, quinidine)	Increased promethazine levels and toxicity	Moderate

Overdose & Toxicity Management

Signs of Toxicity:

Severe CNS depression
Respiratory depression
Hypotension
Tachycardia or bradycardia
Seizures
Extrapyramidal signs
Coma
Mydriasis
Hyperthermia or hypothermia

Emergency Treatment Protocol: Treatment is symptomatic and supportive. Induce emesis if recent oral ingestion and animal is conscious (use caution with CNS depression). Administer activated charcoal and a cathartic. Provide respiratory support (oxygen, ventilation). Treat hypotension with IV fluids and vasopressors (e.g., norepinephrine, phenylephrine; avoid epinephrine). Control seizures with diazepam or barbiturates. Treat extrapyramidal signs with diphenhydramine (if not contraindicated) or anticholinergics. Monitor cardiac function and body temperature.

Food Animal Withdrawal Times

🥩 Meat: 7 days🥛 Milk: 3 days

Withdrawal times are not established for promethazine in food animals; these are suggested based on general phenothiazine data. Extra-label use requires veterinary oversight and extended withdrawal periods may be prudent.

Storage, Handling & Regulatory Information

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

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

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

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Approved for human use; not FDA-approved for veterinary use, but may be used off-label in animals.

Extra-Label (Off-Label) Use: In the US, extra-label use in food animals is permitted under AMDUCA with veterinary oversight, but requires a valid VCPR and extended withdrawal times. Not approved for use in food animals.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Promethazine is a first-generation antihistamine with sedative and antiemetic properties. In veterinary medicine, it is used primarily for allergic conditions, motion sickness, and as a sedative adjunct. However, its efficacy as an antihistamine in animals is variable, and newer antihistamines (e.g., cetirizine, loratadine) may be preferred for allergic dermatitis. Promethazine should be used with caution in animals with cardiovascular disease, seizures, or glaucoma. It can cause significant sedation, which may be desirable in some situations but undesirable in others. For motion sickness, it is best administered 30-60 minutes before travel. In horses, IV administration should be slow to avoid hypotension. In food animals, use is extra-label and requires careful consideration of withdrawal times. Always monitor for adverse effects, especially in young, old, or debilitated animals.

References & Literature

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