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Zyrtec - Drug Description , Side Effects & Drug
Interactions , Warnings & Precautions,Additional
Info,Clinical Pharmacology,
Overdosage & Contraindications ,Indications & Dosage
DESCRIPTION
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 461.82Cetirizine 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; magnesium stearate; povidone; titanium dioxide; hypromellose;
polyethylene glycol; and corn starch.
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 - Side Effects & Drug
Interactions : DVERSE 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 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 were
mild or moderate. In placebo-controlled trials, the incidence of
discontinuations due to adverse reactions in patients receiving
ZYRTEC 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 than placebo was
somnolence. The incidence of somnolence associated with ZYRTEC
was dose related, 6% in placebo, 11% at 5 mg and 14% at 10 mg.
Discontinuations due to somnolence for ZYRTEC were uncommon (1.0%
on ZYRTEC 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 5 and 10 mg in controlled
clinical trials in the United States and that were more common
with ZYRTEC 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. More than 1300 pediatric patients
aged 6 to 11 years with more than 900 treated
with ZYRTEC 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 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 was uncommon
(0.4% on ZYRTEC vs. 1.0% on placebo).
Table 2 lists adverse experiences which were reported for ZYRTEC
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 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
in U. S. trials, including an open adult study of six months duration.
A causal relationship of these infrequent events with ZYRTEC administration
has not been established.
Autonomic
Nervous System : anorexia, flushing, increased salivation, urinary retention.
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, increased sputum, pneumonia,
respiratory disorder, rhinitis, sinusitis, upper respiratory tract
infection.Reproductive
:dysmenorrhea, female breast pain, intermenstrual bleeding, leukorrhea,
menorrhagia, vaginitis.Reticuloendotheliallymphadenopathy.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, enlarged abdomen, face edema, fever, generalized edema, hot
flashes, increased weight,
leg edema, malaise, nasal polyp, pain, pallor, periorbital edema,
peripheral edema, rigors.
PRECAUTIONS
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 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/
m 2 basis, or approximately 7 times the maximum recommended daily
oral dose in infants on a mg/ m 2 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 2 basis, or approximately 3 times the maximum recommended
daily oral dose in infants on a mg/ m 2 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 2 basis, or approximately
equivalent to the maximum recommended daily oral dose in infants
on a mg/ m 2 basis). The clinical significance of these findings
during long-term use of ZYRTEC is not known.
CLINICAL PHARMACOLOGY
Mechanism of Actions
Cetirizine, a human metabolite of hydroxyzine, is
an antihistamine; its principal effects are mediated 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 vivo and ex vivo 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 vivo experiments
in the mouse have shown that systemically administered cetirizine
does not significantly occupy cerebral H1 receptors.
CONTRAINDICATIONS
ZYRTEC is contraindicated in those patients with a known hypersensitivity
to it or any of its ingredients or hydroxyzine.
OVERDOSAGE
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/ m 2 basis, or approximately 40 times the maximum recommended
daily oral dose in infants on a mg/ m 2 basis) and 562 mg/ kg in
rats (approximately 460 times the maximum recommended daily oral
dose in adults on a mg/ m 2 basis, or approximately 190 times the
maximum recommended daily oral dose in infants on a mg/ m 2 basis).
In rodents, the target of acute toxicity was the central nervous
system, and the target of multiple-dose toxicity was the liver.
INDICATIONS AND USAGE
Seasonal Allergic Rhinitis
ZYRTEC 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.
Perennial Allergic Rhinitis
ZYRTEC 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 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
Adults and Children 12 Years and Older: The recommended initial
dose of ZYRTEC is 5 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, with or without food. 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 or 10 mg (1 or 2 teaspoons) 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 syrup in children aged 2 to 5 years is 2.5
mg (½ teaspoon) once daily. The dosage in this age group
can be increased to a maximum dose of 5 mg per day given as 1 teaspoon
(5 mg) once daily, or as ½ teaspoon (2.5 mg) given every
12 hours.
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