Clarinase

Repetab: Each tablet contains 5 mg loratadine and 120 mg pseudoephedrine sulphate.
Excipients with known effect: The quantities of sucrose and lactose monohydrate in each tablet are 173.23 mg and 156.80 mg respectively.
ER tab: Each extended-release tablet contains 10 mg loratadine and 240 mg pseudoephedrine sulphate.
Excipients with known effect: The quantity of sucrose in each extended-release tablet is 13.73 mg.
Excipients/Inactive Ingredients: Repetab: Core: Lactose monohydrate, Maize starch, Povidone (E1201), Magnesium stearate.
Coating: Acacia (E414), Calcium sulphate anhydrous (E516), Calcium sulphate dihydrate (E516), Carnauba wax (E903), Microcrystalline cellulose, Oleic acid, Colophonium, Soap powder, Sucrose, Talc (E553b), Titanium dioxide (E171), White beeswax (E901), Zein.
ER tab: Core: Hydroxypropyl methylcellulose, Ethylcellulose, Calcium phosphate, Povidone, Silicone dioxide, Magnesium stearate.
Coating: Polyethylene glycol 3350, Dye opaspray white, Polyethylene glycol 400, Sucrose, Carnauba wax, White wax.

Pharmacotherapeutic group: Antihistamines - H₁ antagonist. ATC code: R06A X13.
Pharmacotherapeutic group: Nasal decongestants for systemic use group. ATC code: R01BA52.
Pharmacology: Pharmacodynamics: 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 and Clarinase Extended-Release 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.
Pharmacokinetics: 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 (T_max) 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 (C_max) increased for loratadine and its active metabolite as compared to the AUCs and peak plasma levels (C_max) 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 (C_max) 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 breastmilk 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.
Toxicology: 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).

Clarinase Repetabs and Clarinase Extended-Release Tablets are indicated for the relief of symptoms associated with allergic rhinitis and the common cold, including nasal congestion, sneezing, rhinorrhea, pruritus and lacrimation.

Posology: Adults and children 12 years of age and over: Repetab: One Clarinase Repetabs tablet twice daily with a glass of water.
ER tab: One Clarinase Extended-Release Tablet once 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.
Method of administration: Oral use. The prolonged-release tablet or extended-release tablet must be swallowed entirely (without crushing, breaking or chewing it).
The prolonged-release tablet may be taken without regard to mealtime.
The extended-release tablet may be taken with or without food.

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 barbiturates, 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.

Hypersensitivity to the active substances or to any of the excipients listed in Description, or to adrenergic medicinal products.
As Clarinase Repetabs and Clarinase Extended-Release Tablets 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 haemorrhagic stroke or with risk factors which could increase the risk of haemorrhagic stroke. This is due to the alpha-mimetic activity of pseudoephedrine, in combination with other vasoconstrictors such as bromocriptine, 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).

Do not exceed the recommended dosage and the duration of treatment (see Dosage & Administration).
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 Overdosage).
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 linezolid [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 shoul that trd be informedeatment with pseudoephedrine could lead to positive dope-tests.
The administration of Clarinase Repetabs and Clarinase Extended-Release Tablets should be discontinued at least 48 hours before skin tests since antihistamines may prevent or reduce otherwise positive reactions to dermal reactivity index.
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.
Effects on ability to drive and use machines: Clarinase Repetabs and Clarinase Extended-Release Tablets 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.
Use in the Elderly: 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.
Repetab: 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.
ER tab: This medicinal product contains sucrose; thus patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase isomaltase insufficiency should not take this medicine.

Pregnancy: Neither loratadine nor the combination of loratadine and pseudoephedrine were teratogenic in animal studies. The safe use of Clarinase Repetabs and Clarinase Extended-Release Tablets 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 and Clarinase Extended-Release Tablets 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 and Clarinase Extended-Release Tablets should not be used during breast-feeding.
Fertility: There are no data available on male and female fertility.

Repetab: 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). (See Table 1.)

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Other adverse reactions reported during the post-marketing period are listed in the following table. (See Table 2.)

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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. Healthcare professionals are asked to report any suspected adverse reactions.
ER tab: Tabulated list of adverse reactions: The following adverse reactions reported during clinical trials in excess of placebo for 10 mg/240 mg extended-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). (See Table 3.)

Click on icon to see table/diagram/image

Other adverse reactions reported during the post-marketing period are listed in the following table. (See Table 4.)

Click on icon to see table/diagram/image

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. Healthcare professionals are asked to report any suspected adverse reactions.

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 Pharmacology: Pharmacokinetics under Actions).
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.

Store below 25°C. Store in the original packaging in order to protect from excessive moisture. Do not freeze.

Cough & Cold Preparations / Antihistamines & Antiallergics

R01BA52 - pseudoephedrine, combinations ; Belongs to the class of systemic sympathomimetic preparations used as nasal decongestants.

P₁