Zyrtec

Zyrtec information, interactions and side effects, Cetirizine hydrochloride, the active component of ZYRTEC® (cetirizine) 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:

cetiriz

Cetirizine hydrochloride is a white, crystalline powder and is water soluble. ZYRTEC (cetirizine) 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) 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) 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.

INDICATIONS

Seasonal Allergic Rhinitis: ZYRTEC (cetirizine) is indicated for the relief of symptoms associated with seasonal allergic rhinitis due to allergens such asragweed, grass and tree pollens in adults and children 2 years of age and older. Symptoms treated effectively include sneezing, rhinorrhea, nasalpruritus, ocular pruritus, tearing, and redness of the eyes.

Perennial Allergic Rhinitis: ZYRTEC (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 6 months of age and older. Symptoms treated effectively include sneezing, rhinorrhea, postnasal discharge, nasal pruritus, ocular pruritus, and tearing.

Chronic Urticaria: ZYRTEC (cetirizine) is indicated for the treatment of the uncomplicated skin manifestations of chronic idiopathic urticaria in adults and children 6 months of age and older. It significantly reduces the occurrence, severity, and duration of hives and significantly reduces pruritus.

DOSAGE AND ADMINISTRATION

ZYRTEC (cetirizine) can be taken without regard to food consumption. ZYRTEC (cetirizine) 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 (cetirizine) 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 (cetirizine) 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 (cetirizine) 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 (cetirizine) 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 (cetirizine) 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 (cetirizine) 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.

HOW SUPPLIED

ZYRTEC® (cetirizine) 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) ” on one side and “5” on the other. Bottles of 100: NDC 0069-0732-66
10 mg tablets are engraved with “ZYRTEC (cetirizine) ” on one side and “10” on the other. Bottles of 100: NDC 0069-0731-66

STORAGE: Store at 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F).

ZYRTEC (cetirizine) 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) C5” on one side. Boxes of 3 (Blister Cards of 10) NDC 0069-1440-03
10 mg tablets are engraved with “ZYRTEC (cetirizine) C10” on one side. Boxes of 3 (Blister Cards of 10) NDC 0069-1450-03

STORAGE: Store at 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F).

ZYRTEC (cetirizine) syrup is colorless to slightly yellow with a banana-grape flavor. Each teaspoon (5 mL) contains 5 mg cetirizine hydrochloride. ZYRTEC (cetirizine) syrup is supplied as follows:

120 mL amber glass bottles                                    NDC 0069-5530-47
480 mL amber glass bottles                                    NDC 0069-5530-93

STORAGE: Store at 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F) or Store refrigerated, 2-8°C (36-46°F).

SIDE EFFECTS

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) 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) were mild or moderate. In placebo-controlled trials, the incidence of discontinuations due to adverse reactions in patients receiving ZYRTEC (cetirizine) 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) than placebo wassomnolence. The incidence of somnolence associated with ZYRTEC (cetirizine) was dose related, 6% in placebo, 11% at 5 mg and 14% at 10 mg. Discontinuations due to somnolence for ZYRTEC (cetirizine) were uncommon (1.0% on ZYRTEC (cetirizine) vs. 0.6% on placebo). Fatigue and dry mouthalso 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) 5 and 10 mg in controlled clinical trials in the United States and that were more common with ZYRTEC (cetirizine) than placebo.

Table 1.
Adverse Experiences Reported in Patients Aged 12 Years and Older in
Placebo-Controlled United States ZYRTEC (cetirizine) Trials (Maximum Dose of 10 mg)
at Rates of 2% or Greater (Percent Incidence)

 

ADVERSE EXPERIENCE ZYRTEC
(N=2034)
PLACEBO
(N=1612)
Somnolence 13.7 6.3
Fatigue 5.9 2.6
Dry Mouth 5.0 2.3
Pharyngitis 2.0 1.9
Dizziness 2.0 1.2

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) . More than 1300 pediatric patients aged 6 to 11 years with more than 900 treated with ZYRTEC (cetirizine) 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) 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) was uncommon (0.4% on ZYRTEC (cetirizine) vs. 1.0% on placebo).

Table 2 lists adverse experiences which were reported for ZYRTEC (cetirizine) 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) 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.

Table 2.
Adverse Experiences Reported in Pediatric Patients Aged 6 to 11 Years in Placebo-Controlled United States ZYRTEC (cetirizine) Trials (5 or 10 mg Dose) Which Occurred at a Frequency of =2% in Either the 5-mg or the 10-mg ZYRTEC (cetirizine) Group, and More Frequently< Than in the Placebo Group

ADVERSE EXPERIENCES PLACEBO
(N=309)
ZYRTEC
5 MG
(N=161)
10 MG
(N=215)
Headache 12.3% 11.0% 14.0%
Pharyngitis 2.9% 6.2% 2.8%
Abdominal pain 1.9% 4.4% 5.6%
Coughing 3.9% 4.4% 2.8%
Somnolence 1.3% 1.9% 4.2%
Diarrhea 1.3% 3.1% 1.9%
Epistaxis 2.9% 3.7% 1.9%
Bronchospasm 1.9% 3.1% 1.9%
Nausea 1.9% 1.9% 2.8%
Vomiting 1.0% 2.5% 2.3%

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) in U.S. trials, including an open adult study of six months duration. A causal relationship of these infrequent events with ZYRTEC (cetirizine) administration has not been established.

Autonomic Nervous System: anorexia, flushing, increased salivation, urinaryretention.

Cardiovascular: cardiac failure, hypertension, palpitation, tachycardia.

Central and Peripheral Nervous Systems: abnormal coordination, ataxia, confusion, dysphonia, hyperesthesia, hyperkinesia, hypertonia, hypoesthesia,leg cramps, migraine, myelitis, paralysis, paresthesia, ptosis, syncope, tremor, twitching, vertigo, visual field defect.

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

Genitourinary: cystitis, dysuria, hematuria, micturition frequency, polyuria,urinary incontinence, urinary tract infection.

Hearing and Vestibular: deafness, earache, ototoxicity, tinnitus.

Metabolic/Nutritional: dehydration, diabetes mellitus, thirst.

Musculoskeletal: arthralgia, arthritis, arthrosis, muscle weakness, myalgia.

Psychiatric: abnormal thinking, agitation, amnesia, anxiety, decreased libido, depersonalization, depression, emotional lability, euphoria, impaired concentration, insomnia, nervousness, paroniria, sleep disorder.

Respiratory System: bronchitis, dyspnea, hyperventilation, increasedsputum, pneumonia, respiratory disorder, rhinitis, sinusitis, upper respiratory tract infection.

Reproductive: dysmenorrhea, female breast pain, intermenstrual bleeding, leukorrhea, menorrhagia, vaginitis.

Reticuloendothelial: lymphadenopathy.

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

Special Senses: parosmia, taste loss, taste perversion.

Vision: blindness, conjunctivitis, eye pain, glaucoma, loss of accommodation,ocular hemorrhage, xerophthalmia.

Body as a Whole: accidental injury, asthenia, back pain, chest pain, enlargedabdomen, face edema, fever, generalized edema, hot flashes, increased weight, leg edema, malaise, nasal polyp, pain, pallor, periorbital edema, peripheral edema, rigors.

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) has been reported.

Post-Marketing Experience

In the post-marketing period, the following additional rare, but potentially severe adverse events have been reported: aggressive reaction, anaphylaxis, cholestasis, convulsions, glomerulonephritis, hallucinations, hemolytic anemia, hepatitis, orofacial dyskinesia, severe hypotension, stillbirth, suicidal ideation, suicide and thrombocytopenia.

Drug Abuse And Dependence

There is no information to indicate that abuse or dependency occurs with ZYRTEC (cetirizine) .

DRUG INTERACTIONS

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.

PRECAUTIONS

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

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 ofbenign 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 vivomicronucleus 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 notteratogenic 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 (cetirizine) 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 (cetirizine) in nursing mothers is not recommended.

Geriatric Use: Of the total number of patients in clinical studies of ZYRTEC (cetirizine) , 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) 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) 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.

Pediatric Use: The safety of ZYRTEC (cetirizine) has been demonstrated in pediatric patients aged 6 months to 11 years. The safety of ZYRTEC (cetirizine) , 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) 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) for the treatment of allergic rhinitisand chronic idiopathic urticaria in pediatric patients aged 6 months to 11 years is based on an extrapolation of the demonstrated efficacy of ZYRTEC (cetirizine) 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.

This monograph has been modified to include the generic and brand name in many instances.

OVERDOSE

Overdosage has been reported with ZYRTEC (cetirizine) . In one adult patient who took 150 mg of ZYRTEC (cetirizine) , the patient was somnolent but did not display any other clinical signs or abnormal blood chemistry or hematologyresults. In an 18 month old pediatric patient who took an overdose of ZYRTEC (cetirizine) (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) . ZYRTEC (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 (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.

CONTRAINDICATIONS

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

This monograph has been modified to include the generic and brand name in many instances.

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