Hydroxyzine Hydrochloride — Veterinary Vademecum Drug Reference

Dosage & Administration Guidelines

Species	Route	Dose	Frequency	Duration & Clinical Notes
Dog	PO	2.2 mg/kg	q8h	Duration: As needed for pruritus; typically 5-14 days Notes: May be used for anxiety at 1-2 mg/kg q8h. For motion sickness, administer 30-60 minutes before travel.
Cat	PO	2.2-4.4 mg/kg	q12-24h	Duration: As needed for pruritus; typically 5-14 days Notes: Cats may require higher doses; monitor for sedation.
Horse	PO	0.5-1.0 mg/kg	q12h	Duration: As needed for pruritus; typically 5-14 days Notes: Use with caution; may cause CNS depression.
Cattle	PO	Not established	Not established	Duration: Not established Notes: Not commonly used; extra-label use requires veterinary supervision and withdrawal times.
Small Ruminants	PO	Not established	Not established	Duration: Not established Notes: Not commonly used; extra-label use requires veterinary supervision and withdrawal times.
Rabbit	PO	2-5 mg/kg	q8-12h	Duration: As needed Notes: Use with caution; may cause GI stasis.
Bird/Poultry	PO	Not established	Not established	Duration: Not established Notes: Limited data; use with caution.
Exotic/Other	PO	Not established	Not established	Duration: Not established Notes: Use with caution; consult exotic animal specialist.

Clinical Indications & Species Uses

General Indications

Symptomatic relief of pruritus associated with allergic conditions
Sedation
Antiemetic for motion sickness

Dog (Canine)

Pruritus associated with allergic dermatitis
Atopic dermatitis
Urticaria
Motion sickness (as an antiemetic)
Anxiety (as a mild sedative)

Cat (Feline)

Pruritus associated with allergic dermatitis
Atopic dermatitis
Urticaria
Mild sedation for travel or anxiety

Horse (Equine)

Pruritus associated with allergic skin conditions
Urticaria
Insect bite hypersensitivity

Pharmacology & Mechanism of Action

Drug Class: Antihistamine (H1 receptor antagonist) | Pharmacological Group: Piperazine derivative

Mechanism of Action: Hydroxyzine is a first-generation antihistamine that competitively antagonizes histamine at H1 receptors, thereby preventing histamine-mediated effects such as vasodilation, increased vascular permeability, and pruritus. It also has central depressant properties due to its ability to block histamine and acetylcholine receptors in the brain, leading to sedative and anxiolytic effects. Additionally, it exhibits antiemetic and anticholinergic activity.

Pharmacodynamics: Hydroxyzine reduces the effects of histamine on smooth muscle and blood vessels, alleviating pruritus and urticaria. Its sedative effect is attributed to its action on the central nervous system, possibly via inhibition of histamine and acetylcholine in the brain. It also has mild bronchodilator and antispasmodic effects. Onset of action is typically within 15-30 minutes after oral administration, with peak effects at 2 hours.

⚡ Pharmacokinetics Summary

Absorption: Rapidly absorbed from the gastrointestinal tract after oral administration. Peak plasma concentrations occur within 2 hours in dogs and cats. Bioavailability is approximately 80% in dogs.

Distribution: Widely distributed throughout the body, including the skin. Crosses the blood-brain barrier and placenta. Volume of distribution is large. Protein binding is approximately 93% in humans, but may vary in animals.

Metabolism: Extensively metabolized in the liver, primarily via CYP3A4 and other cytochrome P450 enzymes. The major metabolite is cetirizine, which is also an active H1 antagonist.

Excretion: Excreted primarily in the urine as metabolites, with a small amount excreted in feces. In dogs, the elimination half-life is approximately 7-8 hours; in cats, it is approximately 12-14 hours.

Half-Life: Dog: 7-8 hours; Cat: 12-14 hours; Horse: approximately 4-5 hours.

Bioavailability: Oral bioavailability is approximately 80% in dogs; in cats, it is approximately 60-70%.

Protein Binding: Approximately 93% in humans; may be similar in animals.

Available Formulations & Strengths

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

Oral Syrup 10 mg/5 mL (PO)

Oral Capsule 25 mg, 50 mg, 100 mg (PO)

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

Contraindications & Clinical Warnings

Contraindications:

Hypersensitivity to hydroxyzine or other piperazine derivatives
Severe CNS depression
Concurrent use with other CNS depressants (e.g., barbiturates, opioids) may potentiate sedation
Use in animals with glaucoma, prostatic hypertrophy, or urinary retention due to anticholinergic effects
Use in animals with severe hepatic or renal impairment

Warnings & Clinical Precautions:

Use with caution in animals with cardiovascular disease, as it may cause hypotension
May cause paradoxical excitement in some animals, especially cats
Use with caution in pregnant or lactating animals; safety not established
In food animals, observe withdrawal times; extra-label use requires veterinary supervision
May cause drowsiness; caution when animals are engaged in activities requiring alertness
In horses, use with caution as it may cause CNS depression and ataxia

Adverse Effects & Reactions

Common:

Sedation
Drowsiness
Dry mouth
Gastrointestinal upset (vomiting, diarrhea)
Paradoxical excitement (especially in cats)

Serious / Severe:

Hypotension
Arrhythmias
Seizures (rare)
Severe allergic reactions (anaphylaxis)

Rare:

Blood dyscrasias
Hepatotoxicity
Urinary retention

Key Drug Interactions

Interacting Drug / Class	Clinical Effect & Mechanism	Severity
CNS depressants (barbiturates, opioids, benzodiazepines)	Additive sedation and respiratory depression	High
Anticholinergic drugs (atropine, tricyclic antidepressants)	Increased anticholinergic effects (dry mouth, urinary retention)	Moderate
Epinephrine	May potentiate the pressor effects of epinephrine, leading to hypertension and arrhythmias	Moderate
MAO inhibitors	Increased risk of hypotension and CNS depression	Moderate
CYP3A4 inhibitors (e.g., ketoconazole)	May increase hydroxyzine levels, increasing risk of adverse effects	Moderate

Overdose & Toxicity Management

Signs of Toxicity:

Severe sedation
Hypotension
Tachycardia or bradycardia
Seizures
Respiratory depression
Coma

Emergency Treatment Protocol: Treatment is symptomatic and supportive. Induce vomiting if recent ingestion and animal is conscious. Administer activated charcoal to reduce absorption. Provide IV fluids for hypotension. Use vasopressors if needed. Control seizures with diazepam or barbiturates. Monitor cardiac and respiratory function. In severe cases, consider gastric lavage.

Food Animal Withdrawal Times

🥩 Meat: 7 days🥛 Milk: 3 days

Withdrawal times are not officially established for hydroxyzine in food animals. The values provided are conservative estimates based on pharmacokinetic data. Extra-label use in food animals requires veterinary supervision and extended withdrawal periods to ensure food safety.

Storage, Handling & Regulatory Information

Storage Temperature: Store at room temperature (20-25°C / 68-77°F)

Handling & Special Conditions: Protect from moisture. Keep container tightly closed. Do not freeze oral liquid formulations.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Hydroxyzine is FDA-approved for human use, but not specifically approved for veterinary use. However, it is widely used in veterinary medicine as an extra-label drug.

Extra-Label (Off-Label) Use: In the US, extra-label use in food animals is permitted under AMDUCA with veterinary supervision. A withdrawal period must be established by the veterinarian. In non-food animals, extra-label use is common and generally accepted.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Hydroxyzine is a first-generation antihistamine commonly used in veterinary practice for the management of pruritus associated with allergic dermatitis and atopy. It is particularly useful in dogs and cats, providing both antihistaminic and sedative effects, which can be beneficial in reducing self-trauma. The drug is generally well-tolerated, but sedation is a common side effect, which may be desirable in some cases. In cats, paradoxical excitement may occur, requiring dose adjustment or discontinuation. Hydroxyzine is not as effective as glucocorticoids for severe pruritus but may be used as an adjunct or in cases where steroids are contraindicated. It is important to rule out other causes of pruritus (e.g., ectoparasites, infections) before initiating therapy. For food animals, extra-label use should be approached with caution, and withdrawal times must be considered. Overall, hydroxyzine is a valuable tool in the management of allergic skin conditions in companion animals.

References & Literature

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