This leaflet format has been determined by the Ministry of Health and the content has
been checked and approved in 01/2018
1. Name of the medicinal product
Clarinase Repetabs
Tablets
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 5 mg loratadine and 120 mg pseudoephedrine sulphate.
Excipients with known effect: The quantities of sucrose and lactose monohydrate in each
prolonged-release tablet are 173.23 mg and 156.80 mg respectively.
For the full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM
Round, biconvex, lustrous, white, coated tablet.
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Clarinase Repetabs is indicated for the relief of symptoms of seasonal allergic rhinitis when
both the antihistaminic properties and the nasal decongestant activity are desired.
4.2 Posology and method of administration
Posology
Adults and children 12 years of age and over:
One Clarinase Repetabs tablet twice daily with a glass of water.
The duration of treatment should be kept as short as possible and should not be continued
after the symptoms have disappeared. It is advisable to limit treatment to about 10 days, as
during chronic administration the activity of pseudoephedrine may diminish. After
improvement of the congestive condition of the mucosae of the upper airway, treatment
may be maintained with loratadine alone, if necessary.
Paediatric population
The safety and efficacy of Clarinase Repetabs in children below the age of 12 years have not
been established. No data are available. Clarinase Repetabs are not recommended for use in
children below the age of 12 years.
Elderly patients
The combination product should not be administered to patients above 60 years of age.
Patients 60 years or older are more likely to experience adverse reactions to
sympathomimetic medications (see section 4.4).
Patients with renal or hepatic impairment
The combination product should not be used in patients with impaired renal or hepatic
function (see section 4.4).
Method of administration
Oral use. The tablet must be swallowed entirely (without crushing, breaking or chewing it).
The tablet may be taken without regard to mealtime.
4.3 Contraindications
Hypersensitivity to the active substances or to any of the excipients listed in section 6.1, or
to adrenergic medicinal products.
As Clarinase Repetabs contains pseudoephedrine, it is also contraindicated in patients who
are receiving irreversible monoamine oxidase (MAO) inhibitor therapy or during the 2 weeks
following the stopping of such treatment, and in patients with:
- narrow-angle glaucoma
- urinary retention
- cardiovascular diseases such as ischaemic heart disease, tachyarrhythmia and severe
hypertension
- hyperthyroidism
- a history of haemorhagic stroke or with risk factors which could increase the risk of
haemorhagic stroke. This is due to the alpha-mimetic activity of pseudoephedrine, in
combination with other vasoconstrictors such as bromocripitine, pergolide, lisuride,
cabergoline, ergotamine, dihydroergotamine or any other decongestant medication used as
a nasal decongestant, either by oral route or by nasal route (such as phenylpropanolamine,
phenylephrine, ephedrine, oxymetazoline, naphazoline).
4.4 Special warnings and precautions for use
Do not exceed the recommended dosage and the duration of treatment (see section 4.2).
Patients of 60 years or older are more likely to experience adverse reactions to
sympathomimetic medications. The safety and efficacy of the combination have not been
established in this population, and there are insufficient data to give adequate dose
recommendations. The combination product should not be used in patients above 60 years
of age.
Renal or hepatic impairment: The safety and efficacy of the combination have not been
established in patients with impaired renal or hepatic function, and there are insufficient
data to give adequate dose recommendations. The combination product should not be used
in patients with impaired renal or hepatic function.
Patients should be informed that the treatment should be discontinued in case of
hypertension, tachycardia, palpitations or cardiac arrhythmias, nausea or any other
neurologic sign (such as headache or increased headache). Central nervous system
stimulation with convulsions or cardiovascular collapse with accompanying hypotension may
be produced by sympathomimetic amines. These effects may be more likely to occur in
children, the elderly, or in cases of overdose (see section 4.9).
Acute generalized exanthematous pustulosis (AGEP), a form of severe skin reaction, may
occur with pseudoephedrine-containing products in isolated cases. If signs and symptoms
such as fever, erythema, or small (generalized) pustules are observed, patients should
discontinue to use the drug and consult their physician.
Caution should be exercised in patients receiving digitalis, those with cardiac arrhythmias,
hypertension, a history of myocardial infarction, diabetes mellitus, bladder neck obstruction,
or positive anamnesis of bronchospasm.
Use with caution in patients with stenosing peptic ulcer, pyloroduodenal obstruction and
obstruction of the vesical cervix.
Oral administration of pseudoephedrine at the recommended dose can cause other
sympathomimetic effects, such as increased blood pressure, tachycardia or manifestations
of central nervous system excitation.
Concomitant administration of sympathomimetics and reversible MAO inhibitors (such as
linezolide [non-selective] and moclobemide [MAO-A selective] are not recommended.
Caution should also be exercised in patients being treated with other sympathomimetics,
including decongestants, anorexogenics or amphetamine-type psychostimulants,
antihypertensive agents, tricyclic antidepressants and other antihistamines.
Caution should be exercised in patients who are currently being treated with ergot alkaloid
vasoconstrictors.
As with other CNS stimulants, pseudoephedrine sulphate carries the risk of abuse. Increased
doses may ultimately produce toxicity. Continuous use can lead to tolerance resulting in an
increased risk of overdosing. Depression may follow rapid withdrawal.
Perioperative acute hypertension can occur if volatile halogenated anaesthetics are used
during treatment with indirect sympathomimetic agents. Therefore, if surgery is scheduled,
it is preferable to discontinue treatment 24 hours before anaesthesia.
Athletes should be informed that treatment with pseudoephedrine could lead to positive
dope-tests.
This medicinal product contains lactose and sucrose; thus patients with rare hereditary
problems of fructose, galactose intolerance, the Lapp lactase deficiency, glucose-galactose
malabsorption or sucrase isomaltase insufficiency should not take this medicine.
The administration of Clarinase Repetabs should be discontinued at least 48 hours before
skin tests since antihistamines may prevent or reduce otherwise positive reactions to dermal
reactivity index.
4.5 Interaction with other medicinal products and other forms of interaction
When administered concomitantly with alcohol, loratadine has no potentiating effects as
measured by psychomotor performance studies.
CYP3A4 and CYP2D6 inhibitors have been shown to increase loratadine and desloratadine
exposure. However, due to the wide therapeutic index of loratadine, no clinically relevant
interactions are expected and none were observed with co-administration of erythromycin,
ketoconazole and cimetidine in the conducted clinical trials (see section 5.2).
Concurrent administration of monoamine oxidase inhibitors (reversible or irreversible) and
sympathomimetic medicines can cause critical hypertension reactions.
Sympathomimetic medicines may reduce the effect of antihypertensive medicines.
The following combinations are not recommended:
Bromocriptine, cabergoline, lisuride, pergolide: risk of vasoconstriction and increase in blood
pressure.
Dihydroergotamine, ergotamine, methylergometrine: risk of vasoconstriction and increase in
blood pressure.
Reversible and irreversible MAO inhibitor(s): risk of vasoconstriction and increase in blood
pressure.
Other vasoconstrictors used as nasal decongestant, by oral or nasal route, (such as
phenylpropanolamine, phenylephrine, ephedrine, oxymetazoline, naphazoline): risk of
vasoconstriction.
Antacids increase the rate of pseudoephedrine sulphate absorption, kaolin decreases it.
Paediatric population
Interaction studies have only been performed in adults.
4.6 Fertility, pregnancy and lactation
Pregnancy
Neither loratadine nor the combination of loratadine and pseudoephedrine were
teratogenic in animal studies. The safe use of Clarinase Repetabs during pregnancy has not
been established; however experience from a large number of exposed pregnancies in
humans does not reveal any increase in the frequency of malformations as compared to the
incidence in the general population.
Because animal reproduction studies are not always predictive of human response, and due
to the vasoconstrictive properties of pseudoephedrine, Clarinase Repetabs should not be
used during pregnancy.
Breast-feeding
Physico-chemical data suggest excretion of loratadine and pseudoephedrine/metabolites in
human milk. Decreased milk production in nursing mothers has been reported with
pseudoephedrine. A risk to the newborns/infants cannot be excluded. Therefore Clarinase
Repetabs should not be used during breast-feeding.
Fertility
There are no data available on male and female fertility.
4.7 Effects on ability to drive and use machines
Clarinase Repetabs has no or negligible influence on the ability to drive and use machines. In
clinical trials that assessed driving ability, no impairment occurred in patients receiving
loratadine. However, some people very rarely experience drowsiness, which may affect their
ability to drive or use machines.
It is not expected that pseudoephedrine sulphate impairs psychomotor performance.
4.8 Undesirable effects
Tabulated list of adverse reactions
The following adverse reactions reported during clinical trials in excess of placebo for 5
mg/120 mg prolonged-release tablets are listed in the following table by System Organ Class.
Frequencies are defined as very common (> 1/10); common (> 1/100, < 1/10); uncommon (>
1/1000, < 1/100); rare (> 1/10,000, < 1/1000); very rare (< 1/10,000); and not known (cannot
be estimated from the available data).
System Organ Class Frequency Category Adverse Reactions
Metabolism and nutrition Common Thirst
disorders
Psychiatric disorders Common Nervousness, somnolence,
depression, agitation,
anorexia
Very Common Insomnia
Nervous system disorders Uncommon Confusion, tremor, increased
sweating, hot flushes, taste
perversion
Common Dizziness
Eye disorders Uncommon Abnormal lacrimation
Ear and labyrinth disorders Uncommon Tinnitus
Cardiac disorders Uncommon Palpitation
Common Tachycardia
Respiratory, thoracic and Uncommon Epistaxis
mediastinal disorders
Common Pharyngitis, rhinitis
Gastrointestinal disorders Common Constipation, nausea, dry
mouth
Skin and subcutaneous Uncommon Pruritus
tissue disorders
Renal and urinary disorders Uncommon Micturition frequency and
disorder
General disorders and Common Headache, fatigue
administration site
conditions
Other adverse reactions reported during the post-marketing period are listed in the
following table.
System Organ Class Frequency Category Adverse Reactions
Immune system disorders Very rare Hypersensitivity reactions
(such as anaphylaxis, rash,
urticaria, and angioedema)
Nervous system disorders Very rare Vertigo, convulsions
Cardiac disorders Very rare Cardiac arrhythmias
Vascular disorders Very rare Hypertension
Respiratory, thoracic and Very rare Cough, bronchospasm
mediastinal disorders
Hepatobiliary disorders Very rare Abnormal hepatic function
Skin and subcutaneous Very rare Alopecia
tissue disorders
Renal and urinary disorders Very rare Urinary retention
Other adverse reactions that were only reported for loratadine in clinical trials and
during the post- marketing period include increased appetite, rash and gastritis.
From post-marketing experience, isolated cases of acute generalized exanthematous
pustulosis (AGEP), a form of severe skin reaction, have been reported with
pseudoephedrine-containing products.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is
important. It allows continued monitoring of the benefit/risk balance of the medicinal
product. Any suspected adverse events should be reported to the Ministry of Health
according to the Nationa Regulation by using an online form:
http://forms.gov.il/globaldata/getsequence/getsequence.aspx?formType=AdversEffectMedic
@moh.gov.il
4.9 Overdose
Symptoms of overdose
Symptoms of overdose are mostly of a sympathomimetic nature, except for slight sedation
that can be caused by loratadine at doses many times higher than the recommended dose.
Symptoms may vary from CNS depression (sedation, apnoea, diminished mental alertness,
cyanosis, coma, cardiovascular collapse) to CNS stimulation (insomnia, hallucination,
tremors, convulsions) with possible fatal outcome. Other symptoms may include: headache,
anxiety, micturition difficulty, muscle weakness and tenseness, euphoria, excitement,
respiratory failure, cardiac arrhythmias, tachycardia, palpitations, thirst, perspiration,
nausea, vomiting, precordial pain, dizziness, tinnitus, ataxia, blurred vision and hypertension
or hypotension. CNS stimulation is particularly likely in children, as are atropine-like
symptoms (dry mouth, fixed and dilated pupils, flushing, hyperthermia, and gastrointestinal
symptoms). Some patients may present with a toxic psychosis with delusions and
hallucinations.
Management of overdose
In the event of overdosage, start symptomatic and supportive treatment immediately and
maintain it for as long as necessary. Adsorption of active substance remaining in the
stomach may be attempted by administration of active charcoal suspended in water.
Perform gastric lavage with physiologic saline solution, particularly in children. In adults, tap
water can be used. Remove as much as possible of the amount administered before the next
instillation. Loratadine is not removed by haemodialysis and it is not known if loratadine is
eliminated by peritoneal dialysis. After emergency treatment, continue to monitor the
patient medically.
Treatment of the pseudoephedrine overdosage is symptomatic and supportive. Stimulants
(analeptics) must not be used. Hypertension can be controlled with an alpha-blocking agent
and tachycardia with a beta-blocking agent. Short acting barbituates, diazepam or
paraldehyde may be administered to control seizures. Hyperpyrexia, especially in children,
may require treatment with tepid water sponge baths or hypothermia blanket. Apnoea is
treated with respiratory assistance.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: antihistamines – H1 antagonist, ATC code: R06A X13.
Pharmacotherapeutic group: Nasal decongestants for systemic use group, ATC code:
R01BA52.
Mechanism of action
Loratadine is a tricyclic antihistamine with selective, peripheral H1-receptor activity.
Pseudoephedrine sulphate (d-isoephedrine sulphate) is a sympathomimetic agent with
mostly α-mimetic activity in comparison with the β-activity. Pseudoephedrine sulphate
provides a nasal decongestant effect after oral administration due to its vasoconstrictive
action. It has an indirect sympathomimetic effect due primarily to the release of adrenergic
mediators from the post-ganglionic nerve endings.
Pharmacodynamic effects
The pharmacodynamics of Clarinase Repetabs tablets are directly related to that of its
components.
Loratadine has no clinically significant sedative or anticholinergic properties in the majority
of the population and when used at the recommended dosage.
During long-term treatment there were no clinically significant changes in vital signs,
laboratory test values, physical examinations or electrocardiograms.
Loratadine has no significant H2-receptor activity. It does not inhibit norepinephrine uptake
and has practically no influence on cardiovascular function or on intrinsic cardiac pacemaker
activity.
5.2 Pharmacokinetic properties
Loratadine
Absorption
Loratadine is rapidly and well-absorbed. Concomitant ingestion of food can delay slightly the
absorption of loratadine but without influencing the clinical effect. The bioavailability of
loratadine and of the active metabolite are dose proportional.
Increase in plasma concentrations of loratadine has been reported after concomitant use
with ketoconazole, erythromycin, and cimetidine in controlled trials, but without clinically
significant changes (including electrocardiographic).
Distribution
Loratadine is highly bound (97 % to 99 %) and its active major metabolite desloratadine (DL)
moderately bound (73 % to 76 %) to plasma proteins.
In healthy subjects, plasma distribution half-lives of loratadine and its active metabolite are
approximately 1 and 2 hours, respectively.
Biotransformation
After oral administration, loratadine undergoes an extensive first pass metabolism, mainly
by CYP3A4 and CYP2D6. The major metabolite-desloratadine (DL) is pharmacologically active
and responsible for a large part of the clinical effect. Loratadine and DL achieve maximum
plasma concentrations (Tmax) between 1–1.5 hours and 1.5–3.7 hours after administration,
respectively.
Elimination
Approximately 40 % of the dose is excreted in the urine and 42 % in the faeces over a 10 day
period and that, mainly in the form of conjugated metabolites. Approximately 27 % of the
dose is eliminated in the urine during the first 24 hours. Less than 1 % of the active
substance is excreted unchanged in active form, as loratadine or DL.
The mean elimination half-lives are 8.4 hours (range = 3 to 20 hours) for loratadine and 28
hours (range = 8.8 to 92 hours) for the active metabolite.
Renal impairment
In patients with chronic renal impairment, both the area under the curve (AUC) and peak
plasma levels (Cmax) increased for loratadine and its active metabolite as compared to the
AUCs and peak plasma levels (Cmax) of patients with normal renal function. The mean
elimination half-lives of loratadine and its active metabolite were not significantly different
from those observed in normal subjects. Haemodialysis does not have an effect on the
pharmacokinetics of loratadine or its active metabolite in subjects with chronic renal
impairment.
Hepatic impairment
In patients with chronic alcoholic liver disease, the AUC and peak plasma levels (Cmax) of
loratadine were double while the pharmacokinetic profile of the active metabolite was not
significantly changed from that in patients with normal liver function. The elimination half-
lives for loratadine and its metabolite were 24 hours and 37 hours, respectively, and
increased with increasing severity of liver disease.
Elderly
The pharmacokinetic profile of loratadine and its metabolites is comparable in healthy adult
volunteers and in healthy geriatric volunteers.
Pseudoephedrine sulphate
Absorption
After oral administration, pseudoephedrine sulphate is rapidly and completely absorbed.
Onset of action occurs within 30 minutes and a dose of 60 mg has a decongestive action
lasting for 4 to 6 hours.
Food may increase the amount of loratadine absorbed, but without clinically significant
results. This is not observed with pseudoephedrine.
Distribution
Pseudoephedrine is presumed to cross the placenta and the haematoencephalic barrier.
The active substance is excreted in breast milk of lactating women.
Biotransformation
Pseudoephedrine sulphate undergoes incomplete hepatic metabolism by N-demethylation
to an inactive metabolite.
Elimination
Its elimination half-life in humans, at an approximate urinary pH of 6, ranges from 5 to 8
hours. The active substance and its metabolite are excreted in urine, 55-75 % of the
administered dose is excreted unchanged. The rate of excretion is accelerated and the
duration of action decreased in acidic urine (pH5). In case of alkalinization of the urine, a
partial resorption takes place.
5.3 Preclinical safety data
Non-clinical data for loratadine reveal no special hazard for humans based on conventional
studies of safety, pharmacology, repeated dose toxicity, genotoxicity and carcinogenicity.
Toxicity for the combination: In acute and multiple-dose studies, the combination of
loratadine/pseudoephedrine sulphate exhibited a low order of toxicity. The combination
was not more toxic than their individual components, and observed effects were generally
related to the pseudoephedrine component.
In reproductive toxicity studies of loratadine, no teratogenic effects were observed.
However, prolonged parturition and reduced viability of offspring were observed in rats at
plasma levels (AUC) 10 times higher than those achieved with clinical doses.
During reproductive toxicity studies, the combination of loratadine/pseudoephedrine was
not teratogenic when administered orally to rats at doses up to 150 mg/kg/day (30 times the
proposed clinical dose) and rabbits at doses up to 120 mg/kg/day (24 times the proposed
clinical dose).
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Core:
Lactose monohydrate
Corn starch
Povidone
Magnesium stearate
Coating:
Sucrose
Calcium sulphate anhydrous
Calcium sulphate dihydrate
Talc
Gum rosin nelio
Acacia
Zein
Titanium dioxide
Oleic acid
Cellulose microcrystalline
Soap powder
Carnauba wax
White wax
Incompatibilities
Not applicable.
6.3 Shelf life
The expiry date of the product is indicated on the packaging materials.
6.4 Special precautions for storage
Do not store above 25°C. Store in the original blister packaging in order to protect from
moisture. Do not freeze.
6.5 Nature and contents of container
Blister strip consisting of a clear, transparent PVC-PCTFE film (PVC in contact with product)
and a lidding of aluminium foil with vinyl heat seal coating. The blister strips are enclosed in
cartons in pack sizes of 2, 4, 10, 14, 20, 28, 30 and 50 tablets.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
Any unused medicinal product or waste material should be disposed of in accordance with
local requirements.
6.7 MANUFACTURER
SCHERING-PLOUGH LAB. NV,
HEIST-OP-DEN-BERG
BELGIUM
6.8 REGISTRATION HOLDER
Bayer Israel Ltd.
36 Hacharash St.
Hod Hasharon 45240
