CETIRIZINE HCL

CETIRIZINE HCL

2nd GENERATION ANTIHISTAMINE

Chemistry/Synonyms

Cetirizine HCl occurs as a white to almost white, crystalline powder that is freely soluble in water. A 5% solution has a pH of 1.2 – 1.8.

Cetirizine may also be known as: UCB-P071, P-071, cetirizina, cetirizini, cetirizin, ceterizino, or Zyrtec®; many internationally registered trade names are available.

Prescriber Highlights

Oral, relatively non-sedating antihistamine

Limited clinical experience in veterinary medicine; recommended dosages for dogs & cats vary widely but the drug appears well tolerated

Potentially may cause vomiting, hypersalivation, or somnolence in small animals

Expensive when compared to 1st generation antihistamines; generic products becoming available

Uses/Indications

Cetirizine is a H1 receptor blocking antihistamine agent that may be useful for the adjunctive treatment of histamine-mediated pruritic conditions in dogs or cats.

Pharmacology/Actions

Cetirizine, a human metabolite of hydroxyzine, is a piperazine-class non-sedating (when compared to first generation drugs) antihistamine.

It selectively inhibits peripheral H1 receptors. Cetirizine does not possess significant anticholinergic or anti-serotonergic effects.

Tolerance to its antihistaminic effects is thought not to occur.

Pharmacokinetics

No specific information was located for the pharmacokinetics of cetirizine in dogs. In a study performed in cats (Papich, Schooley et al. 2006) after an oral dose of 5 mg, volume of distribution was 0.26 L/kg and clearance about 0.3 mL/L/minute. Terminal elimination half-life was approximately 11 hours. The mean plasma concentrations remained above 0.85 mcg/mL (a concentration reported to be effective for humans) for 24 hours after dosing.

After oral administration to humans, cetirizine peak concentrations occur in about one hour. Food can delay, but not affect the extent of, absorption. It is 93% bound to human plasma proteins and brain levels are approximately 10% of those found in plasma.

Approximately 80% is excreted in the urine, primarily as unchanged drug. Terminal elimination half-life is around 8 hours; antihistaminic effect generally persists for 24 hours after a dose.

Contraindications/Precautions/Warnings

No specific information is available for veterinary patients. In humans, cetirizine is contraindicated in patients hypersensitive to it or hydroxyzine. Dosage adjustment is recommended in humans with severe renal or hepatic impairment, or older than 76 years of age.

The combination product containing pseudoephedrine is not appropriate for use in dogs or cats.

Adverse Effects

Cetirizine appears well tolerated in dogs and cats. Vomiting or hypersalivation after dosing have been reported in some dogs.

Drowsiness has been reported in small dogs at higher dosages.

In humans, the primary adverse effects reported have been drowsiness (13%) and dry mouth (5%). Rarely, hypersensitivity reactions or hepatitis have been reported.

Reproductive/Nursing Safety

In pregnant mice, rats, and rabbits, dosages of approximately 40X, 180X, and 220X respectively, of the human dose when compared on mg/m2 basis, caused no teratogenic effects. In humans, the FDA categorizes cetirizine as category B for use during pregnancy

(Animal studies have not yet demonstrated risk to the fetus, but there are no adequate studies in pregnant women; or animal studies have shown an adverse effect, but adequate studies in pregnant women have not demonstrated a risk to the fetus in the first trimester of pregnancy,

and there is no evidence of risk in later trimesters.)

In Beagles, approximately 3% of a dose was excreted into milk.

Although probably safe for use in nursing veterinary patients, the manufacturer does not recommend using cetirizine in nursing women.

Overdosage/Acute Toxicity

Limited information is available. Reported minimum lethal oral doses for mice and rats are 237 mg/kg (95X human adult dose on a mg/m2 basis) and 562 mg/kg (460X human adult dose on a mg/m2 basis), respectively. Unlike the earlier non-sedating antihistamines, terfenadine and astemizole (both no longer available in the USA), cetirizine does not appreciably prolong the QT interval on ECG at high serum levels.

Overdoses of cetirizine products that also contain pseudoephedrine (Zyrtec-D 12 Hour®) may be serious. It is advised to contact an animal poison control center in this event.

Drug Interactions

The following drug interactions have either been reported or are theoretical in humans or animals receiving cetirizine and may be of significance in veterinary patients:

CNS DEPRESSANTS: Additive CNS depression if used with cetirizine

Laboratory Considerations

None noted, however discontinue medication well in advance of any hypersensitivity skin testing

Doses

DOGS:

a) For atopic dermatitis: 1 mg/kg PO once daily with or without food. Satisfactory control of pruritus in 18% of dogs evaluated in the study.

b) For atopic dermatitis: 5 – 10 mg (total dose) PO once daily

c) For allergic dermatitis: 1 mg/kg PO q12h

CATS:

a) For adjunctive treatment of non-responsive chronic rhinosinusitis: 5 mg (total dose) PO q12h

b) For adjunctive treatment of eosinophilic dermatopathies: 5mg (total dose) PO q12h

c) For adjunctive treatment of pruritus: 2.5 – 5 mg (total dose) PO once daily.

Monitoring

Clinical efficacy

Adverse effects (vomiting, somnolence)

Client Information

Warn clients of the potential costs

Potential adverse effects include GI effects (vomiting, hypersalivation) and somnolence

May be given without regard to feeding status

Storage/Stability

Tablets should be stored at 20 – 25°C; excursions are permitted to 15 – 30°C. The oral syrup may be stored at room temperature or in the refrigerator.

Dosage Forms/Regulatory Status

VETERINARY-LABELED PRODUCTS: None

The ARCI (Racing Commissioners International) has designated this drug as a class 4 substance.

HUMAN-LABELED PRODUCTS:

Cetirizine HCl Tablets (film-coated): 5 mg & 10 mg; Zyrtec® (Pfizer), generic; (Rx)

Cetirizine HCl Chewable Tablets (grape flavor): 5 mg & 10 mg; Zyrtec® (Pfizer), generic; (Rx)

Cetirizine HCl Syrup: 1 mg/mL (banana-grape flavor) in 120 and 480 mL; Zyrtec® (Pfizer); (Rx)

Cetirizine HCl 5 mg with Pseudoephedrine HCl 120