First-Generation Antihistamines

Chlorpheniramine

Propylamine-derivative antihistamine

Therapeutic dose:

• Dogs: 2–8 mg/dog, PO, q 8–12 h

• Cats: 1–2 mg/cat, PO, q 8–12 h

Toxic dose:

• Mild clinical signs (depression, GI upset) can occur at < 1 mg/kg.

• Peak plasma concentrations in 2–6 h

• Substantial first-pass effect

• Metabolized in liver

• Chlorpheniramine and metabolites primarily excreted in urine

Within 2–4 h of ingestion

Clemastine

Ethanolamine-derivative antihistamine

1.35 mg clemastine fumarate is equivalent to 1 mg clemastine.

Therapeutic dose:

• Dogs: 0.05–0.1 mg/kg, PO, q 12 h

• Cats: 0.34–0.68 mg/cat, PO, q 12 h

Toxic dose:

• Unknown; LD₅₀ in dogs is 175 mg/kg.

• Low oral bioavailability in dogs (3%, vs 20–70% in humans)

• Peak plasma concentrations in 2–5 h

• Highly protein bound

• Extensively metabolized in liver

• Eliminated in urine

Within 30–60 min of ingestion

Dimenhydrinate and diphenhydramine

Ethanolamine-derivative antihistamine

Therapeutic dose:

• Dimenhydrinate: Dogs/cats: 4–8 mg/kg, PO, IM, or IV, q 8 h

• Diphenhydramine: Dogs/cats: 2–4 mg/kg, PO, IM, or IV, q 8 h

Toxic dose:

• Unknown; LD₅₀ in rats is 1,320 mg/kg, and in mice, 203 mg/kg.

• Peak plasma concentrations in 1–5 h

• First-pass effect

• Metabolized in liver

• Eliminated in urine

Within 30–60 min of ingestion

Doxylamine succinate

Ethanolamine-derivative antihistamine

Therapeutic dose:

• Dogs and cats: 1.1–2.2 mg/kg, PO, q 8–12 h

Toxic dose:

• Unknown; LD₅₀ in rats is 600 mg/kg, and in mice, 160 mg/kg.

• Peak plasma concentrations in 2–3 h

• Metabolized in liver

• Eliminated in urine

Within 30–60 min of ingestion

Hydroxyzine

Piperazine-derivative antihistamine

Therapeutic dose:

• Dogs: 2–3 mg/kg, PO, q 8–12 h

• Cats: 5–10 mg/cat, PO, q 12 h

Toxic dose:

• Unknown; mild clinical signs can occur at therapeutic doses.

• Peak plasma concentrations in 3 h

• Extensively metabolized in liver

Within 2 h of ingestion

Meclizine

Piperazine-derivative antihistamine

Therapeutic dose:

• Dogs: 12.5–50 mg/dog, PO, q 24 h

• Cats: 6.25–12.5 mg/cat, PO, q 24 h

Toxic dose:

• Unknown; mild clinical signs can occur at < 33 mg/kg in dogs.

• Peak plasma concentrations in 2–3 h

• Metabolized in liver

• Eliminated in urine

Within 9 h of ingestion

Promethazine

Phenothiazine-derivative antihistamine

Therapeutic dose:

• Dogs: 0.2–0.5 mg/kg, PO, q 6–8 h for motion sickness

• Cats: 2 mg/kg, IM, once

Toxic dose:

• Not well established.

• Low oral bioavailability in dogs (10%)

• Metabolized in liver

• Eliminated in urine

Within 30 min of ingestion,

CNS depression is more common than agitation.