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.2011 ‫ אוגוסט‬:‫ עלון מאושר‬."‫"פורמט עלון זה נקבע ע"י משרד הבריאות ותוכנו נבדק ואושר‬
“This leaflet format has been determined by the Ministry of Health and the content thereof has been
checked and approved.” Date of approval: August 2011.
OTAREX
TABLETS
Composition
Each scored tablet contains:
Active Ingredient
Hydroxyzine hydrochloride
25 mg
Other Ingredients
Lactose monohydrate*, microcrystalline cellulose, colloidal silicon dioxide,
magnesium stearate, FD&C yellow No. 6 aluminium lake 15-18%, D&C yellow No. 10
aluminium lake 18-24%.
* Lactose content: 135.2 mg per tablet.
Mechanism of Action
Otarex is a rapid-acting tranquilizer unrelated chemically to the phenothiazines. It
induces a calming effect in anxious, tense and psychoneurotic patients, usually
without impairing mental alertness.
Bronchodilator activity and antihistaminic and analgesic effects have been
demonstrated experimentally and confirmed clinically.
Otarex is also used as 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. Clinical effects are
usually noted within 15-30 minutes following oral administration.
Indications
Anxiety and tension.
Pruritus.
Behavioral disturbances in children.
Preoperative sedation.
Contraindications
Known hypersensitivity to cetirizine, to other piperazine derivatives, to
aminophylline, or to ethylenediamine, or to any other ingredient of the preparation.
Pregnancy and lactation.
Patients with porphyria.
Warnings
Otarex should be administered cautiously in patients with increased potential for
convulsions.
Dosage adjustments may be required if Otarex is used simultaneously with other
central nervous system depressant drugs or with drugs having anticholinergic
properties .
The concomitant use with alcohol should be avoided .
Caution is needed in patients who have a known predisposing factor to cardiac
arrhythmia, or who are concomitantly treated with a potentially arrhythmogenic drug.
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In patients with pre-existing prolonged QT intervals, use of 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
(see Contraindications)
Hydroxyzine is contraindicated in pregnancy.
Animal studies have shown reproductive toxicity.
Hydroxyzine crosses the placental barrier leading to higher fetal than maternal
concentrations.
To date, no relevant epidemiological data are available relating to exposure to
hydroxyzine during pregnancy.
In neonates whose mothers received hydroxyzine during late pregnancy and/or
labour, the following events were observed immediately or only a few hours after
birth : hypotonia, movement disorders including extrapyramidal disorders, clonic
movements, CNS depression, neonatal hypoxic conditions, or urinary retention.
Therefore, this product should not be used during pregnancy
Use in Breastfeeding
(see Contraindications)
It is not known whether this drug is excreted 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
In patients with hepatic dysfunction, it is recommended to reduce the daily dose by
33%.
As hydroxyzine is metabolized in the liver, an increase in hydroxyzine blood
concentrations may be expected when hydroxyzine is co-administered with other
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 renal function. It is
uncertain whether the drug may accumulate or have other adverse effects in such
patients. Otarex is completely metabolized and one of the metabolites is the active
metabolite cetirizine. Cetirizine is renally excreted and clearance is reduced in
patients with moderate renal impairment and on dialysis compared to normal
volunteers.
Use in the Elderly
In the elderly, it is advised to start with half the recommended dose due to a
prolonged action.
Precautions
Since hydroxyzine possesses antihistaminic effects (including an atropine-like
action), this drug should be used with caution in patients with a history of or suffering
from bronchial asthma, increased intraocular pressure, bladder outflow obstruction,
decreased gastro-intestinal motility, myasthenia gravis, or dementia, hyperthyroidism,
cardiovascular disease or hypertension.
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In other conditions, antihistamines are contraindicated. These include: narrowangle glaucoma, stenosing peptic ulcer, symptomatic prostatic hypertrophy, bladder
neck obstruction, pyloroduodenal obstruction.
Patients who experience drowsiness as a result of Otarex therapy should be
cautioned against engaging in potentially-hazardous activities requiring mental
alertness, such as driving a car or operating machinery.
Adverse Reactions
Undesirable effects are mainly related to CNS depressant or paradoxical CNS
stimulation effects, to anticholinergic activity, or to hypersensitivity reactions.
A Clinical trials
The following table list the relevant undesirable effects reported in placebocontrolled clinical trials for hydroxyzine and including 735 subjects exposed to
hydroxyzine up to 50 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 ( 1/10000 to <1/1000); very rare (<1/10000), not known (cannot be
estimated from the available data).
System Organ Class Adverse event preferred term
Frequency
Nervous system
disorders
Somnolence
Very common
Headache
Common
Dizziness
Uncommon
Insomnia
Uncommon
Disturbance in attention
Uncommon
Dry mouth
Common
Constipation
Uncommon
Nausea
Uncommon
Fatigue
Common
Asthenia
Uncommon
Gastrointestinal
disorders
General disorders
and administration
site conditions
B Post-marketing experience
The following table lists, per body system, the additional undesirable adverse
reactions reported during marketed use of the drug. No frequency can be estimated
from post-marketing reporting of events.
Immune system disorders :
Hypersensitivity, anaphylactic shock
Psychiatric disorders :
Agitation, confusion, disorientation, hallucination
Nervous system disorders :
Sedation, tremor, convulsions, dyskinesia
Eye disorders :
Accommodation disorder, vision blurred
Cardiac disorders :
Tachycardia
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Vascular disorders :
Hypotension
Respiratory, thoracic and mediastinal disorders :
Bronchospasm
Gastrointestinal disorders :
Vomiting
Skin and subcutaneous tissue disorders :
Pruritus, erythematous rash, maculo-papular rash, urticaria, dermatitis, angioneurotic
oedema, sweating increased, fixed drug eruption
Renal and urinary disorders :
Urinary retention
General disorders and administration site conditions :
Malaise, pyrexia
Investigations :
Liver function tests abnormal
Drug Interactions
Since hydroxyzine possesses antihistaminic effects, the potential of sharing
antihistamines drug interactions exists. Examples include:
Hydroxyzine/Alcohol/CNS Depressants/(including Tricyclic Antidepressants):
Antihistamines may have additive effects when used concurrently with alcohol or
other CNS depressants, 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
the anticholinergic (drying) effects of antihistamines. Therefore, concurrent use with
monoamine oxidase (MAO) inhibitor therapy or within 14 days of discontinuation of
such therapy should be avoided.
Hydroxyzine/Anticholinergic Agents or Other Agents Possessing Anticholinergic
Activity: Concurrent use of antihistamines with these agents may lead to a
potentiation of the anticholinergic effects. Therefore, caution should be exercised and
patients should be advised to promptly report occurrence of gastrointestinal
problems, since paralytic ileus may occur upon concurrent therapy of antihistamines
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: In rats, hydroxyzine antagonised the anticonvulsant action of
phenytoin.
Hydroxyzine/Cimetidine: Cimetidine 600 mg bid has been shown to increase the serum
concentrations of hydroxyzine by 36% and to decrease peak concentrations of the
metabolite cetirizine by 20%.
Hydroxyzine is an inhibitor of cytochrome P450 2D6 and may cause at high doses
drug-drug interactions with CYP2D6 substrates.
Hydroxyzine has no inhibitory effect at 100 µM on UDP-glucuronyl transferase
isoforms 1A1 and 1A6 in human liver microsomes. It inhibits cytochrome P450
2C9/C10, 2C19 and 3A4 isoforms at concentrations well above peak plasma
concentrations. The metabolite cetirizine at 100 µM has no inhibitory effect on human
liver cytochrome P450 (1A2, 2A6, 2C9/C10, 2C19, 2D6, 2E1 and 3A4) and UDPglucuronyl transferase isoforms. Therefore, this product is unlikely to impair the
metabolism of drugs which are substrates for these enzymes.
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Diagnostic Interference
The administration of hydroxyzine may interfere with measurements of urinary 17hydroxycorticosteroids.
The treatment should be stopped at least 5 days before allergy testing or
methacholine bronchial challenge, to avoid effects on the test results.
Dosage and Administration
1 tablet 3 times daily.
Overdosage
Manifestations
Symptoms observed after an important overdose are mainly associated with
excessive anticholinergic load, 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.
Treatment
Airway, breathing and circulatory status must be closely monitored with continuous
ECG recording and an adequate oxygen supply should be available. Cardiac and
blood pressure monitoring should be maintained until the patient is free of symptoms
for 24 hours. Patients with altered mental status should be checked for simultaneous
intake of other drugs or alcohol and should be given oxygen, naloxone, glucose, and
thiamine if deemed necessary.
Norepinephrine or metaraminol should be used if vasopressor is needed.
Epinephrine should not be used.
Syrup of ipecac should not be administered in symptomatic patients or those who
could rapidly become obtunded, comatose or convulsing, as this could lead to
aspiration pneumonitis. Gastric lavage with prior endotracheal intubation may be
performed if a clinically significant ingestion has occurred. Activated charcoal may be
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.
Literature data indicate that, in the presence of severe, life-threatening, intractable
anticholinergic effects unresponsive to other agents, a therapeutic trial dose of
physostigmine may be useful. Physostigmine should not be used just to keep the
patient awake. If cyclic antidepressants have been coingested, use of physostigmine
may precipitate seizures and intractable cardiac arrest. Also avoid physostigmine in
patients with cardiac conduction defects.
Registration Numbers
025 08 20756 00
025 08 20756 01.
Storage
Store in a dry place below 25C.
Manufacturer
Teva Pharmaceutical Industries Ltd
P.O.Box 3190, Petach Tikva
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