Antihistamines, histamine H1-receptor antagonist.

Cetirizine, a human metabolite of hydroxyzine, is an antihistamine; its principal effects are medicated via selective inhibition of peripheral H1 receptors. The antihistaminic activity of cetirizine has been clearly documented in a variety of animal and human models. In vitro and ex vitro animal models have shown negligible anticholinergic and antiserotonergic activity. In clinical studies, however, dry mouth was more common with cetirizine than with placebo. In vitro receptor binding studies have shown no measurable affinity for other than H1 receptors. Autoradiographic studies with radiolabeled cetirizine in the rat have shown negligible penetration into the brain. Ex vitro experiments in the mouse have shown that systemically administered cetirizine does not significantly occupy cerebral H1 receptors.

Cetirizine was rapidly absorbed with a time to maximum concentration of approximately 1 hour following oral administration of tablets or syrup in adults. Comparable bioavailability was found between the tablet and syrup dosage forms. When healthy volunteers were administered multiple doses of cetirizine a mean peak plasma concentration of 311 ng/ml was observed. No accumulation was observed. Cetirizine pharmacokinetics were linear for oral doses ranging from 5-60 mg. Food had no effect on the extent of cetirizine exposure but Tmax was delayed by 1.7 hours and Cmax was decreased by 23% in the presence of food.

Cetirizine is indicated for the relief of symptoms associated with seasonal allergic rhinitis due to allergens such as ragweed, grass and tree pollens in adults and children 2 years of age and older. Symptoms treated effectively include sneezing, rhinorrhea, nasal pruritus, ocular pruritus, tearing and redness of the eyes.

Cetirizine is indicated for the relief of symptoms associated with perennial allergic rhinitis due to allergens such as dust mites, animal dander and molds in adults and children 2 years of age and older. Symptoms treated effectively include sneezing, rhinorrhea, postnasal discharge, nasal pruritus, ocular pruritus and tearing.

Cetirizine is indicated for the treatment of the uncomplicated skin manifestations of chronic idiopathic urticaria in adults and children 2 years of age and older. It significantly reduces the occurrence, severity and duration of hives and significantly reduces pruritus.

Overdosage has been reported with cetirizine. In one adult patient who took 150 mg of cetirizine, the patient was somnolent but did not display any other clinical signs or abnormal blood chemistry or hematology results. In an 18 month old pediatric patient who took an overdosage of cetirizine, restlessness and irritability were observed initially; this was followed by drowsiness. Should overdose occur, treatment should be symptomatic or supportive, taking into account any concomitantly ingested medications. There is no known specific antidote to cetirizine. Cetirizine is not effectively removed by dialysis and dialysis will be ineffective unless a dialyzable agent has been concomitantly ingested. The acute minimal lethal oral doses were 237 mg/kg in mice and 562 mg/kg in rats. In rodents, the target of acute toxicity was the central nervous system and the target of multiple-dose toxicity was the liver.

Controlled and uncontrolled clinical trials conducted in the US and Canada included more than 6000 patients aged 12 years and older, with more than 3900 receiving cetirizine at doses of 5-20 mg/day. The duration of treatment ranged from 1 week to 6 months with a mean exposure of 30 days.

Most adverse reactions reported during therapy with cetirizine were mild or moderate. In placebo-controlled trials, the incidence of discontinuations due to adverse reactions in patients receiving cetirizine 5 or 10 mg was not significantly different from placebo.

Body as a whole : Accidental injury, asthenia, back pain, chest pain, enlarged abdomen, face edema, fever, generalized edema, hot flashes, increased weight, leg edema, malaise, nasal polyp, pain, pallor, periorbital edema, peripheral edema, rigors.

Autonomic Nervous system : Anorexia, flushing, increased salivation, urinary retention.

Cardiovascular : Cardiac failure, hypertension, palpitation, tachycardia

Gastrointestinal : Abnormal hepatic function, aggravated tooth caries, constipation, dyspepsia, eructation, flatulence, gastritis, hemorrhoids, increased appetite, melena, rectal hemorrhage, stomatitis including ulcerative stomatitis, togue discoloration, tongue edema.

Skin : Acne, alopecia, angioedema, bullous eruption, dermatitis, dry skin, eczema, erythematous rash, furunculosis, hyperkeratosis, hypertrichosis, increased sweating, maculopapular rash, photosensitivity raction, photosensitivity toxic reaction, pruritus, purpura, rash, seborrhea, skin disorder, skin nodule, urticaria.

In clinical trials, the occurrence of somnolence has been reported in some patients taking cetirizine; due caution should therefore be exercised when driving a car or operating potentially dangerous machinery. Concurrent use of cetirizine with alcohol or other CNS depressants should be avoided because additional reductions in alertness and additional impairment of CNS performance may occur.

The effectiveness of cetirizine for the treatment of seasonal and perennial allergic rhinitis and chronic idiopathic urticaria in pediatric patients aged 2-11 years is based on an extrapolation of the demonstrated efficacy of cetirizine in adults in these conditions and the likelihood that the disease course, pathophysiology and the drug’s effect are substantially similar between these two populations. The recommended doses for the pediatric population are based on cross-study comparisons of the pharmacokinetics and pharmacodynamics of cetirizine in adult and pediatric subjects and on the safety profile of cetirizine in both adult and pediatric patients at doses equal to or higher than the recommended doses.

The cetirizine AUC and Cmax in pediatric subjects aged 2-5 years who received a single dose of 5 of 10 mg of cetirizine syrup were estimated to be intermediate between that observed in adults who received a single dose of 10 mg cetirizine tablets and those who received a single dose of cetirizine tablets.

The safety and effectiveness of cetirizine in pediatric patients under the age of 2 years have not yet been established.

Cetirizine is contraindicated in those patients with a known hypersensitivity to it or any of its ingredients or hydroxyzine.

Keep in cool, dry place and protect from moisture and light. Store at a temperature of 25°C.