Zyrtec Tablets

Cetirizine hydrochloride, the active component of ZYRTEC® tablets and syrup, is an orally active and selective H1-receptor antagonist. The chemical name is (±) - [2- [4- [ (4-chlorophenyl)phenylmethyl] -1- piperazinyl] ethoxy]acetic acid, dihydrochloride. Cetirizine hydrochloride is a racemic compound with an empirical formula of C21H25ClN2O3•2HCl. The molecular weight is 461.82 and the chemical structure is shown below:

Cetirizine hydrochloride is a white, crystalline powder and is water soluble. Zyrtec Tablets are formulated as white, film-coated, rounded-off rectangular shaped tablets for oral administration and are available in 5 and 10 mg strengths. Inactive ingredients are: lactose monohydrate; microcrystalline cellulose; colloidal silicon dioxide; croscarmellose sodium; magnesium stearate; titanium dioxide; hypromellose; and polyethylene glycol.

ZYRTEC chewable tablets are formulated as purple round tablets for oral administration and are available in 5 and 10 mg strengths. Inactive ingredients of the chewable tablets are: acesulfame potassium; artificial grape flavor; betadex, NF; blue dye; colloidal silicon dioxide; lactose monohydrate; magnesium stearate; mannitol; microcrystalline cellulose; natural flavor; red dye (carmine).

ZYRTEC syrup is a colorless to slightly yellow syrup containing cetirizine hydrochloride at a concentration of 1 mg/mL (5 mg/5 mL) for oral administration. The pH is between 4 and 5. The inactive ingredients of the syrup are: banana flavor; glacial acetic acid; glycerin; grape flavor; methylparaben; propylene glycol; propylparaben; sodium acetate; sugar syrup; and water.

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

Activities Requiring Mental Alertness

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

Drug-Drug Interactions

No clinically significant drug interactions have been found with theophylline at a low dose, azithromycin, pseudoephedrine, ketoconazole, or erythromycin. There was a small decrease in the clearance of cetirizine caused by a 400-mg dose of theophylline; it is possible that larger theophylline doses could have a greater effect.

Carcinogenesis, Mutagenesis and Impairment of Fertility

In a 2-year carcinogenicity study in rats, cetirizine was not carcinogenic at dietary doses up to 20 mg/kg (approximately 15 times the maximum recommended daily oral dose in adults on a mg/m2 basis, or approximately 7 times the maximum recommended daily oral dose in infants on a mg/m2 basis). In a 2-year carcinogenicity study in mice, cetirizine caused an increased incidence of benign liver tumors in males at a dietary dose of 16 mg/kg (approximately 6 times the maximum recommended daily oral dose in adults on a mg/m2 basis, or approximately 3 times the maximum recommended daily oral dose in infants on a mg/m2 basis). No increase in the incidence of liver tumors was observed in mice at a dietary dose of 4 mg/kg (approximately 2 times the maximum recommended daily oral dose in adults on a mg/m2 basis, or approximately equivalent to the maximum recommended daily oral dose in infants on a mg/m2 basis). The clinical significance of these findings during long-term use of ZYRTEC is not known.

Cetirizine was not mutagenic in the Ames test, and not clastogenic in the human lymphocyte assay, the mouse lymphoma assay, and in vivo micronucleus test in rats.

In a fertility and general reproductive performance study in mice, cetirizine did not impair fertility at an oral dose of 64 mg/kg (approximately 25 times the maximum recommended daily oral dose in adults on a mg/m2 basis).

Pregnancy Category B

In mice, rats, and rabbits, cetirizine was not teratogenic at oral doses up to 96, 225, and 135 mg/kg, respectively (approximately 40, 180 and 220 times the maximum recommended daily oral dose in adults on a mg/m2 basis). There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, ZYRTEC should be used during pregnancy only if clearly needed.

Nursing Mothers

In mice, cetirizine caused retarded pup weight gain during lactation at an oral dose in dams of 96 mg/kg (approximately 40 times the maximum recommended daily oral dose in adults on a mg/m2 basis). Studies in beagle dogs indicated that approximately 3% of the dose was excreted in milk. Cetirizine has been reported to be excreted in human breast milk. Because many drugs are excreted in human milk, use of ZYRTEC in nursing mothers is not recommended.

Geriatric Use

Of the total number of patients in clinical studies of ZYRTEC, 186 patients were 65 years and older, and 39 patients were 75 years and older. No overall differences in safety were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out. With regard to efficacy, clinical studies of ZYRTEC for each approved indication did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently than younger patients.

ZYRTEC is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. (See Geriatric Patients and Renal Impairment subsections in CLINICAL PHARMACOLOGY .)

Pediatric Use

The safety of ZYRTEC has been demonstrated in pediatric patients aged 6 months to 11 years. The safety of ZYRTEC, at daily doses of 5 or 10 mg, has been demonstrated in 376 pediatric patients aged 6 to 11 years in placebo-controlled trials lasting up to four weeks and in 254 patients in a non-placebo-controlled 12-week trial. The safety of cetirizine has been demonstrated in 168 patients aged 2 to 5 years in placebo-controlled trials of up to 4 weeks duration. On a mg/kg basis, most of the 168 patients received between 0.2 and 0.4 mg/kg of cetirizine HCl. The safety of cetirizine in 399 patients aged 12 to 24 months has been demonstrated in a placebo-controlled 18-month trial, in which the average dose was 0.25 mg/kg bid, corresponding to a range of 4 to 11 mg/day. The safety of ZYRTEC syrup has been demonstrated in 42 patients aged 6 to 11 months in a placebo-controlled 7-day trial. The prescribed dose was 0.25 mg/kg bid, which corresponded to a mean of 4.5 mg/day, with a range of 3.4 to 6.2 mg/day.

The effectiveness of ZYRTEC for the treatment of allergic rhinitis and chronic idiopathic urticaria in pediatric patients aged 6 months to 11 years is based on an extrapolation of the demonstrated efficacy of ZYRTEC in adults with these conditions and the likelihood that the disease course, pathophysiology and the drug's effect are substantially similar between these two populations. Efficacy is extrapolated down to 6 months of age for perennial allergic rhinitis and down to 2 years of age for seasonal allergic rhinitis because these diseases are thought to occur down to these ages in children. 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 6 to 23 months who received a mean of 2.3 mg in a single dose, and in subjects aged 2 to 5 years who received a single dose of 5 mg of cetirizine syrup and in pediatric subjects aged 6 to 11 years who received a single dose of 10 mg of cetirizine syrup were estimated to be intermediate between that observed in adults who received a single dose of 10 mg of cetirizine tablets and those who received a single dose of 20 mg of cetirizine tablets.

The safety and effectiveness of cetirizine in pediatric patients under the age of 6 months have not been established.

Overdosage has been reported with ZYRTEC. In one adult patient who took 150 mg of ZYRTEC, 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 overdose of ZYRTEC (approximately 180 mg), 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 ZYRTEC. ZYRTEC 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 (approximately 95 times the maximum recommended daily oral dose in adults on a mg/m2 basis, or approximately 40 times the maximum recommended daily oral dose in infants on a mg/m2 basis) and 562 mg/kg in rats (approximately 460 times the maximum recommended daily oral dose in adults on a mg/m2 basis, or approximately 190 times the maximum recommended daily oral dose in infants on a mg/m2 basis). In rodents, the target of acute toxicity was the central nervous system, and the target of multiple-dose toxicity was the liver.

ZYRTEC can be taken without regard to food consumption. ZYRTEC is available as 5 mg and 10 mg tablets, 1 mg/mL syrup, and 5 mg and 10 mg chewable tablets which can be taken with or without water.

Adults and Children 12 Years and Older

The recommended initial dose of ZYRTEC is 5 mg or 10 mg per day in adults and children 12 years and older, depending on symptom severity. Most patients in clinical trials started at 10 mg. ZYRTEC is given as a single daily dose. The time of administration may be varied to suit individual patient needs.

Children 6 to 11 Years

The recommended initial dose of ZYRTEC in children aged 6 to 11 years is 5 mg or 10 mg once daily depending on symptom severity. The time of administration may be varied to suit individual patient needs.

Children 2 to 5 Years

The recommended initial dose of ZYRTEC in children aged 2 to 5 years is 2.5 mg (½ teaspoon) syrup once daily. The dosage in this age group can be increased to a maximum dose of 5 mg per day given as 1 teaspoon syrup once a day or one ½ teaspoon syrup given every 12 hours, or one 5 mg chewable tablet once a day.

Children 6 months to <2 years

The recommended dose of ZYRTEC syrup in children 6 months to 23 months of age is 2.5 mg (½ teaspoon) once daily. The dose in children 12 to 23 months of age can be increased to a maximum dose of 5 mg per day, given as ½ teaspoon (2.5 mg) every 12 hours. Syrup is recommended for children under the age of 2 years.

Dose Adjustment for Renal and Hepatic Impairment

In patients 12 years of age and older with decreased renal function (creatinine clearance 11–31 mL/min), patients on hemodialysis (creatinine clearance less than 7 mL/min), and in hepatically impaired patients, a dose of 5 mg once daily is recommended. Similarly, pediatric patients aged 6 to 11 years with impaired renal or hepatic function should use the lower recommended dose. Because of the difficulty in reliably administering doses of less than 2.5 mg (½ teaspoon) of ZYRTEC syrup and in the absence of pharmacokinetic and safety information for cetirizine in children below the age of 6 years with impaired renal or hepatic function, its use in this impaired patient population is not recommended.

Dose Adjustment for Geriatric Patients

In patients 77 years of age and older, a dose of 5 mg once daily is recommended.