Israel - English - Ministry of Health
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" עעבקנהזןולעטמרופ " רשואוקדבנונכותותואירבהדרשמי ." רשואמןולע : טסוגוא 2011 .
“This leaflet format has been determined by the Ministryof Healthand thecontent thereof has been
checked and approved.” Dateof approval:August2011.
Each scored tablet contains:
Hydroxyzine hydrochloride 25 mg
Lactosemonohydrate * , microcrystalline cellulose, colloidalsilicondioxide,
magnesiumstearate, FD&C yellow No.6 aluminium lake 15-18%, D&C yellow No.10
aluminium lake 18-24%.
* Lactose content: 135.2 mgper tablet.
Mechanism of Action
Otarex is a rapid-acting tranquilizer unrelated chemicallytothephenothiazines.It
inducesa calming effect in anxious, tense and psychoneurotic patients, usually
without impairing mental alertness.
Bronchodilatoractivity and antihistaminic and analgesic effects have been
demonstrated experimentallyand confirmed clinically.
Otarexisalsousedas an antiemetic, as an adjunct to pre- and post-operative
medication, and as a mild anticholinergic agent.
Otarex has a wide margin of safety and is well tolerated.
Hydroxyzine is rapidly absorbed from the gastrointestinal tract.Clinicaleffectsare
usually noted within 15-30 minutes following oral administration.
Anxiety and tension.
Behavioral disturbances in children.
Known hypersensitivity to cetirizine, to other piperazinederivatives,to
aminophylline, or to ethylenediamine, or toany other ingredient of the preparation.
Pregnancy and lactation.
Patients with porphyria.
Otarex should be administered cautiously in patients with increased potential for
Dosage adjustments may be required if Otarex is used simultaneouslywithother
central nervous system depressant drugsor with drugs havinganticholinergic
The concomitant use with alcohol should be avoided .
Caution is needed in patients who have a knownpredisposingfactortocardiac
arrhythmia, or who are concomitantly treated with a potentially arrhythmogenic drug.
In patients with pre-existing prolonged QT intervals,useof alternative treatments is
to be considered.
Otarex contains lactose. Patients with rare hereditiary problems of galactose
intolerance, the Lapp lactase deficiency or glucose-galactose mal-absorption should
not take this medicine.
Use in Pregnancy
Hydroxyzine is contraindicated in pregnancy.
Animal studies have shown reproductive toxicity.
Hydroxyzinecrossestheplacental barrier leading to higher fetal than maternal
To date, no relevant epidemiological data are availablerelatingtoexposureto
hydroxyzine during pregnancy.
In neonates whose mothers received hydroxyzine during late pregnancy and/or
labour, the following events were observed immediately or only afewhoursafter
birth : hypotonia, movement disorders including extrapyramidaldisorders,clonic
movements, CNS depression, neonatal hypoxic conditions, or urinary retention.
Therefore, this product should not be used during pregnancy
Use in Breastfeeding
Itisnotknown whether this drug isexcreted in human milk. Since many drugs are
so excreted, hydroxyzine should not be given to nursing mothers.
Use in Pediatrics
This product is not intended for use in children.
Use in Patients with Impaired Hepatic Function
Inpatientswithhepaticdysfunction,itis recommended to reduce the daily dose by
As hydroxyzine is metabolized in the liver,anincreaseinhydroxyzineblood
concentrations may be expected when hydroxyzine isco-administeredwithother
drugs known to be potent inhibitors of liver enzymes.
Use in Patients with Impaired Renal Function
Otarex should be used with caution in patients with impaired renalfunction.Itis
uncertainwhether the drug may accumulate or have other adverse effects in such
patients. Otarex is completely metabolized and one of the metabolitesistheactive
metabolitecetirizine.Cetirizineis renally excreted and clearance is reduced in
patients with moderate renal impairment and on dialysis compared to normal
Use in the Elderly
In the elderly, it is advised to start with half the recommended doseduetoa
Sincehydroxyzinepossessesantihistaminic effects (including an atropine-like
action), this drug should be used with caution in patients with a historyoforsuffering
from bronchial asthma, increased intraocularpressure,bladderoutflowobstruction,
decreased gastro-intestinal motility, myasthenia gravis, or dementia, hyperthyroidism,
cardiovascular disease or hypertension.
Inotherconditions,antihistamines are contraindicated. These include: narrow-
angleglaucoma,stenosingpeptic ulcer, symptomatic prostatic hypertrophy, bladder
neck obstruction, pyloroduodenal obstruction.
Patientswhoexperience drowsiness as a result of Otarex therapy should be
cautioned against engaging in potentially-hazardous activitiesrequiringmental
alertness, such as driving a car or operating machinery.
Undesirable effects are mainly related to CNSdepressantorparadoxicalCNS
stimulation effects, to anticholinergic activity, or to hypersensitivity reactions.
A Clinical trials
The following table list the relevantundesirableeffectsreportedinplacebo-
controlledclinicaltrialsfor hydroxyzine and including 735 subjects exposed to
hydroxyzineupto50 mg daily. The frequency has been estimated using the following
definitions: very common (1/10); common (1/100 to < 1/10); uncommon (1/1000
to <1/100); rare (1/10000to<1/1000);very rare (<1/10000), not known (cannot be
estimated from the available data).
System Organ ClassAdverse event preferred term Frequency
InsomniaUncommon Nervous system
Disturbance in attention Uncommon
Dry mouth Common
FatigueCommon General disorders
site conditions AstheniaUncommon
B Post-marketing experience
Thefollowingtablelists,per body system, the additional undesirable adverse
reactionsreported during marketed use of the drug. No frequency can be estimated
from post-marketing reporting of events.
Immune systemdisorders :
Hypersensitivity, anaphylactic shock
Psychiatric disorders :
Agitation, confusion, disorientation, hallucination
Nervous systemdisorders :
Sedation, tremor, convulsions, dyskinesia
Eye disorders :
Accommodation disorder, vision blurred
Cardiac disorders :
Vascular disorders :
Respiratory, thoracic and mediastinal disorders :
Gastrointestinal disorders :
Skin and subcutaneous tissue disorders :
Pruritus,erythematousrash,maculo-papular rash, urticaria, dermatitis, angioneurotic
oedema, sweating increased, fixed drug eruption
Renal and urinary disorders :
General disorders and administration site conditions :
Liver function tests abnormal
Since hydroxyzine possesses antihistaminic effects, the potentialofsharing
antihistamines drug interactions exists. Examples include:
Hydroxyzine/Alcohol/CNS Depressants/(including Tricyclic Antidepressants):
Antihistaminesmayhaveadditive effects when used concurrently with alcohol or
otherCNSdepressants,e.g. barbiturates, hypnotics, sedatives, tranquilizers,
antianxiety agents, narcotic analgesics.
Hydroxyzine/ Monoamine Oxidase (MAO)Inhibitors: Concurrent use of
antihistamines with monoamine oxidase (MAO) inhibitors may prolong and intensify
theanticholinergic(drying)effects of antihistamines. Therefore, concurrent use with
monoamine oxidase (MAO) inhibitor therapyor within 14 days of discontinuation of
such therapy should be avoided.
Hydroxyzine/AnticholinergicAgentsor Other Agents Possessing Anticholinergic
Activity: Concurrent use of antihistamines with theseagentsmayleadtoa
potentiation of the anticholinergic effects. Therefore, caution should be exercised and
patients should be advised to promptly report occurrence ofgastrointestinal
problems, since paralytic ileus may occur uponconcurrenttherapyofantihistamines
and anticholinergic agents.
Hydroxyzine/Betahistine/Anticholinesterase Drugs :Hydroxyzine antagonizes the
effects of betahistine, and of anticholinesterase drugs.
Hydroxyzine/Epinephrine : ounteracts the epinephrine pressor action.
Hydroxyzine/Phenytoin :Inrats,hydroxyzine antagonised the anticonvulsant action of
Hydroxyzine/Cimetidine: Cimetidine 600 mg bid has been shown to increasetheserum
concentrationsofhydroxyzineby36% and to decrease peak concentrations of the
metabolite cetirizine by 20%.
Hydroxyzine is an inhibitor of cytochrome P450 2D6 and may cause athighdoses
drug-drug interactions with CYP2D6 substrates.
Hydroxyzinehasnoinhibitoryeffect at 100 µM on UDP-glucuronyl transferase
isoforms 1A1 and 1A6 in human liver microsomes.ItinhibitscytochromeP
2C9/C10, 2C19 and 3A4 isoforms at concentrations well above peakplasma
concentrations. The metabolite cetirizine at 100 µM has noinhibitoryeffectonhuman
liver cytochrome P
(1A2,2A6, 2C9/C10, 2C19, 2D6, 2E1 and 3A4) and UDP-
glucuronyltransferaseisoforms.Therefore, this product is unlikely to impair the
metabolism of drugs which are substrates for these enzymes.
Theadministrationof hydroxyzine may interfere with measurements of urinary 17-
The treatment should be stopped at least 5daysbeforeallergytestingor
methacholine bronchial challenge, to avoid effects on the test results.
Dosage and Administration
1 tablet 3 times daily.
Symptomsobservedafteranimportant overdose are mainly associated with
excessiveanticholinergicload,CNS depression or CNS paradoxical stimulation.
They include nausea, vomiting, tachycardia, pyrexia, somnolence, impaired pupillary
reflex,tremor,confusion,or hallucination. This may be followed by depressed level of
consciousness,respiratory depression, convulsions, hypotension, or cardiac
arrhythmia. Deepening coma and cardiorespiratory collapse may ensue.
Airway, breathing and circulatory status must becloselymonitoredwithcontinuous
ECG recording and an adequate oxygen supply should be available. Cardiac and
bloodpressuremonitoringshould be maintained until the patient is free of symptoms
for24 hours. Patients with altered mental status should be checked for simultaneous
intakeofotherdrugsoralcoholand should be given oxygen, naloxone, glucose, and
thiamine if deemed necessary.
Norepinephrineormetaraminol should be used if vasopressor is needed.
Epinephrine should not be used.
Syrup of ipecac should not be administered in symptomatic patients or thosewho
could rapidly become obtunded, comatose or convulsing, as thiscouldleadto
aspiration pneumonitis. Gastric lavage with prior endotracheal intubationmaybe
performed if a clinically significant ingestion has occurred. Activated charcoal maybe
left in the stomach but there are scant data to support its efficacy.
It is doubtful that hemodialysis or hemoperfusion would be of any value.
There is no specific antidote.
Literaturedataindicatethat, in the presence of severe, life-threatening, intractable
anticholinergiceffects unresponsive to other agents, a therapeutic trial dose of
physostigmine may be useful. Physostigmine should not be used just to keepthe
patientawake.Ifcyclic antidepressants have been coingested, use of physostigmine
may precipitate seizures and intractable cardiac arrest.Alsoavoidphysostigminein
patients with cardiac conduction defects.
025 08 20756 00
025 08 20756 01.
Store in a dry place below 25 C.
Teva Pharmaceutical Industries Ltd
P.O.Box 3190, Petach Tikva