Zyrtec Information
Zyrtec (Cetirizine hcl) Description
Cetirizine hydrochloride, the active component of Zyrtec (Cetirizine hcl) ® tablets and syrup, is an orally active and selective H-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 CHClNO•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 (Cetirizine hcl) 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 (Cetirizine hcl) 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 (Cetirizine hcl) 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 (Cetirizine hcl) Clinical Pharmacology
Studies in 69 adult normal volunteers (aged 20 to 61 years) showed that Zyrtec (Cetirizine hcl) at doses of 5 and 10 mg strongly inhibited the skin wheal and flare caused by the intradermal injection of histamine. The onset of this activity after a single 10-mg dose occurred within 20 minutes in 50% of subjects and within one hour in 95% of subjects; this activity persisted for at least 24 hours. Zyrtec (Cetirizine hcl) at doses of 5 and 10 mg also strongly inhibited the wheal and flare caused by intradermal injection of histamine in 19 pediatric volunteers (aged 5 to 12 years) and the activity persisted for at least 24 hours. In a 35-day study in children aged 5 to 12, no tolerance to the antihistaminic (suppression of wheal and flare response) effects of Zyrtec (Cetirizine hcl) was found. In 10 infants 7 to 25 months of age who received 4 to 9 days of cetirizine in an oral solution (0.25 mg/kg bid), there was a 90% inhibition of histamine-induced (10 mg/mL) cutaneous wheal and 87% inhibition of the flare 12 hours after administration of the last dose. The clinical relevance of this suppression of histamine-induced wheal and flare response on skin testing is unknown.
The effects of intradermal injection of various other mediators or histamine releasers were also inhibited by cetirizine, as was response to a cold challenge in patients with cold-induced urticaria. In mildly asthmatic subjects, Zyrtec (Cetirizine hcl) at 5 to 20 mg blocked bronchoconstriction due to nebulized histamine, with virtually total blockade after a 20-mg dose. In studies conducted for up to 12 hours following cutaneous antigen challenge, the late phase recruitment of eosinophils, neutrophils and basophils, components of the allergic inflammatory response, was inhibited by Zyrtec (Cetirizine hcl) at a dose of 20 mg.
In four clinical studies in healthy adult males, no clinically significant mean increases in QTc were observed in Zyrtec (Cetirizine hcl) treated subjects. In the first study, a placebo-controlled crossover trial, Zyrtec (Cetirizine hcl) was given at doses up to 60 mg per day, 6 times the maximum clinical dose, for 1 week, and no significant mean QTc prolongation occurred. In the second study, a crossover trial, Zyrtec (Cetirizine hcl) 20 mg and erythromycin (500 mg every 8 hours) were given alone and in combination. There was no significant effect on QTc with the combination or with Zyrtec (Cetirizine hcl) alone. In the third trial, also a crossover study, Zyrtec (Cetirizine hcl) 20 mg and ketoconazole (400 mg per day) were given alone and in combination. Zyrtec (Cetirizine hcl) caused a mean increase in QTc of 9.1 msec from baseline after 10 days of therapy. Ketoconazole also increased QTc by 8.3 msec. The combination caused an increase of 17.4 msec, equal to the sum of the individual effects. Thus, there was no significant drug interaction on QTc with the combination of Zyrtec (Cetirizine hcl) and ketoconazole. In the fourth study, a placebo-controlled parallel trial, Zyrtec (Cetirizine hcl) 20 mg was given alone or in combination with azithromycin (500 mg as a single dose on the first day followed by 250 mg once daily). There was no significant increase in QTc with Zyrtec (Cetirizine hcl) 20 mg alone or in combination with azithromycin.
In a four-week clinical trial in pediatric patients aged 6 to 11 years, results of randomly obtained ECG measurements before treatment and after 2 weeks of treatment showed that Zyrtec (Cetirizine hcl) 5 or 10 mg did not increase QTc versus placebo. In a one week clinical trial (N=86) of Zyrtec (Cetirizine hcl) syrup (0.25 mg/kg bid) compared with placebo in pediatric patients 6 to 11 months of age, ECG measurements taken within 3 hours of the last dose did not show any ECG abnormalities or increases in QTc interval in either group compared to baseline assessments. Data from other studies where Zyrtec (Cetirizine hcl) was administered to patients 6–23 months of age were consistent with the findings in this study.
The effects of Zyrtec (Cetirizine hcl) on the QTc interval at doses higher than 10 mg have not been studied in children less than 12 years of age.
In a six-week, placebo-controlled study of 186 patients (aged 12 to 64 years) with allergic rhinitis and mild to moderate asthma, Zyrtec (Cetirizine hcl) 10 mg once daily improved rhinitis symptoms and did not alter pulmonary function. In a two-week, placebo-controlled clinical trial, a subset analysis of 65 pediatric (aged 6 to 11 years) allergic rhinitis patients with asthma showed Zyrtec (Cetirizine hcl) did not alter pulmonary function. These studies support the safety of administering Zyrtec (Cetirizine hcl) to pediatric and adult allergic rhinitis patients with mild to moderate asthma.
Zyrtec (Cetirizine hcl) Contraindications
Zyrtec (Cetirizine hcl) is contraindicated in those patients with a known hypersensitivity to it or any of its ingredients or hydroxyzine.
Zyrtec (Cetirizine hcl) Precautions
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/m basis, or approximately 7 times the maximum recommended daily oral dose in infants on a mg/m 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/m basis, or approximately 3 times the maximum recommended daily oral dose in infants on a mg/m 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/m basis, or approximately equivalent to the maximum recommended daily oral dose in infants on a mg/m basis). The clinical significance of these findings during long-term use of Zyrtec (Cetirizine hcl) is not known.
Cetirizine was not mutagenic in the Ames test, and not clastogenic in the human lymphocyte assay, the mouse lymphoma assay, and 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/m basis).
Of the total number of patients in clinical studies of Zyrtec (Cetirizine hcl) , 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 (Cetirizine hcl) 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 (Cetirizine hcl) 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 and subsections in
The safety of Zyrtec (Cetirizine hcl) has been demonstrated in pediatric patients aged 6 months to 11 years. The safety of Zyrtec (Cetirizine hcl) , 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 (Cetirizine hcl) 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 (Cetirizine hcl) 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 (Cetirizine hcl) 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.
Zyrtec (Cetirizine hcl) Adverse Reactions
Controlled and uncontrolled clinical trials conducted in the United States and Canada included more than 6000 patients aged 12 years and older, with more than 3900 receiving Zyrtec (Cetirizine hcl) at doses of 5 to 20 mg per 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 Zyrtec (Cetirizine hcl) were mild or moderate. In placebo-controlled trials, the incidence of discontinuations due to adverse reactions in patients receiving Zyrtec (Cetirizine hcl) 5 or 10 mg was not significantly different from placebo (2.9% vs. 2.4%, respectively).
The most common adverse reaction in patients aged 12 years and older that occurred more frequently on Zyrtec (Cetirizine hcl) than placebo was somnolence. The incidence of somnolence associated with Zyrtec (Cetirizine hcl) was dose related, 6% in placebo, 11% at 5 mg and 14% at 10 mg. Discontinuations due to somnolence for Zyrtec (Cetirizine hcl) were uncommon (1.0% on Zyrtec (Cetirizine hcl) vs. 0.6% on placebo). Fatigue and dry mouth also appeared to be treatment-related adverse reactions. There were no differences by age, race, gender or by body weight with regard to the incidence of adverse reactions.
Table 1 lists adverse experiences in patients aged 12 years and older which were reported for Zyrtec (Cetirizine hcl) 5 and 10 mg in controlled clinical trials in the United States and that were more common with Zyrtec (Cetirizine hcl) than placebo.
In addition, headache and nausea occurred in more than 2% of the patients, but were more common in placebo patients.
Pediatric studies were also conducted with Zyrtec (Cetirizine hcl) . More than 1300 pediatric patients aged 6 to 11 years with more than 900 treated with Zyrtec (Cetirizine hcl) at doses of 1.25 to 10 mg per day were included in controlled and uncontrolled clinical trials conducted in the United States. The duration of treatment ranged from 2 to 12 weeks. Placebo-controlled trials up to 4 weeks duration included 168 pediatric patients aged 2 to 5 years who received cetirizine, the majority of whom received single daily doses of 5 mg. A placebo-controlled trial 18 months in duration included 399 patients aged 12 to 24 months treated with cetirizine (0.25 mg/kg bid), and another placebo-controlled trial of 7 days duration included 42 patients aged 6 to 11 months who were treated with cetirizine (0.25 mg/kg bid).
The majority of adverse reactions reported in pediatric patients aged 2 to 11 years with Zyrtec (Cetirizine hcl) were mild or moderate. In placebo-controlled trials, the incidence of discontinuations due to adverse reactions in pediatric patients receiving up to 10 mg of Zyrtec (Cetirizine hcl) was uncommon (0.4% on Zyrtec (Cetirizine hcl) vs. 1.0% on placebo).
Table 2 lists adverse experiences which were reported for Zyrtec (Cetirizine hcl) 5 and 10 mg in pediatric patients aged 6 to 11 years in placebo-controlled clinical trials in the United States and were more common with Zyrtec (Cetirizine hcl) than placebo. Of these, abdominal pain was considered treatment-related and somnolence appeared to be dose-related, 1.3% in placebo, 1.9% at 5 mg and 4.2% at 10 mg. The adverse experiences reported in pediatric patients aged 2 to 5 years in placebo-controlled trials were qualitatively similar in nature and generally similar in frequency to those reported in trials with children aged 6 to 11 years.
In the placebo-controlled trials of pediatric patients 6 to 24 months of age, the incidences of adverse experiences were similar in the cetirizine and placebo treatment groups in each study. Somnolence occurred with essentially the same frequency in patients who received cetirizine and patients who received placebo. In a study of 1 week duration in children 6–11 months of age, patients who received cetirizine exhibited greater irritability/fussiness than patients on placebo. In a study of 18 months duration in patients 12 months and older, insomnia occurred more frequently in patients who received cetirizine compared to patients who received placebo (9.0% v. 5.3%). In those patients who received 5 mg or more per day of cetirizine as compared to patients who received placebo, fatigue (3.6% v. 1.3%) and malaise (3.6% v. 1.8%) occurred more frequently.
The following events were observed infrequently (less than 2%), in either 3982 adults and children 12 years and older or in 659 pediatric patients aged 6 to 11 years who received Zyrtec (Cetirizine hcl) in U.S. trials, including an open adult study of six months duration. A causal relationship of these infrequent events with Zyrtec (Cetirizine hcl) administration has not been established.
Occasional instances of transient, reversible hepatic transaminase elevations have occurred during cetirizine therapy. Hepatitis with significant transaminase elevation and elevated bilirubin in association with the use of Zyrtec (Cetirizine hcl) has been reported.
Zyrtec (Cetirizine hcl) Drug Abuse And Dependence
There is no information to indicate that abuse or dependency occurs with Zyrtec (Cetirizine hcl) .
Zyrtec (Cetirizine hcl) Overdosage
Overdosage has been reported with Zyrtec (Cetirizine hcl) . In one adult patient who took 150 mg of Zyrtec (Cetirizine hcl) , 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 (Cetirizine hcl) (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 (Cetirizine hcl) . Zyrtec (Cetirizine hcl) 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/m basis, or approximately 40 times the maximum recommended daily oral dose in infants on a mg/m basis) and 562 mg/kg in rats (approximately 460 times the maximum recommended daily oral dose in adults on a mg/m basis, or approximately 190 times the maximum recommended daily oral dose in infants on a mg/m basis). In rodents, the target of acute toxicity was the central nervous system, and the target of multiple-dose toxicity was the liver.
Zyrtec (Cetirizine hcl) Dosage And Administration
Zyrtec (Cetirizine hcl) can be taken without regard to food consumption. Zyrtec (Cetirizine hcl) 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.
Zyrtec (Cetirizine hcl) How Supplied
Zyrtec (Cetirizine hcl) tablets are white, film-coated, rounded-off rectangular shaped containing 5 mg or 10 mg cetirizine hydrochloride.
5 mg tablets are engraved with "Zyrtec (Cetirizine hcl) " on one side and "5" on the other. Bottles of 100: NDC 0069-0732-66
10 mg tablets are engraved with "Zyrtec (Cetirizine hcl) " on one side and "10" on the other. Bottles of 100: NDC 0069-0731-66
Zyrtec (Cetirizine hcl) chewable tablets are purple round tablets containing 5 mg or 10 mg cetirizine hydrochloride. The tablets are packaged in blister cards as follows:
5 mg tablets are engraved with "Zyrtec (Cetirizine hcl) C5" on one side. Boxes of 3 (Blister Cards of 10) NDC 0069-1440-03
10 mg tablets are engraved with "Zyrtec (Cetirizine hcl) C10" on one side. Boxes of 3 (Blister Cards of 10) NDC 0069-1450-03
Zyrtec (Cetirizine hcl) syrup is colorless to slightly yellow with a banana-grape flavor. Each teaspoon (5 mL) contains 5 mg cetirizine hydrochloride. Zyrtec (Cetirizine hcl) syrup is supplied as follows:
120 mL amber glass bottles NDC 0069-5530-47 480 mL amber glass bottles NDC 0069-5530-93
Zyrtec (Cetirizine hcl)
