Alersis

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ALE R SIS (ALERSIS)

Composition:

Active substance: desloratadine;

1 ml of solution contains desloratadine 0.5 mg;

Excipients: sodium benzoate (E 211), sodium saccharin, sorbitol (E 420), propylene glycol, citric acid anhydrous, sodium citrate anhydrous, hydroxyethylcellulose, orange flavor, purified water.

Pharmaceutical form. Oral solution.

Main physicochemical properties: clear or slightly opalescent, practically colorless solution with an orange odor.

Pharmacotherapeutic group. Systemic antihistamines.

ATC code R06A X27.

Pharmacological Properties.

Pharmacodynamics.

Desloratadine is a potent, selective blocker of peripheral histamine H1-receptors, which does not exhibit sedative effects. Desloratadine is the primary active metabolite of loratadine.

After oral administration, Alercys selectively blocks peripheral H1-histamine receptors, as the drug barely penetrates the blood-brain barrier.

Numerous studies have shown that in addition to its antihistaminic activity, Alercys demonstrates anti-allergic and anti-inflammatory properties. It has been established that Alercys suppresses the cascade of various reactions underlying allergic inflammation, namely:

• release of proinflammatory cytokines, including IL-4, IL-6, IL-8, IL-13;
• release of proinflammatory chemokines, such as RANTES;
• production of superoxide anion by activated polymorphonuclear neutrophils;
• adhesion and chemotaxis of eosinophils;
• expression of adhesion molecules, such as P-selectin;
• IgE-dependent release of histamine, prostaglandin D2, and leukotriene C4;
• acute allergic bronchospasm and allergic cough in animal studies.

The safety of Alercys in children has been demonstrated in three clinical trials. The drug was administered to children aged 6 months to 11 years requiring antihistamine therapy at daily doses of 1 mg (age group 6 to 11 months), 1.25 mg (age group 1 to 5 years), or 2.5 mg (age group 6 to 11 years). The treatment was well tolerated, as confirmed by clinical laboratory test results, vital function status, and ECG data (including QT interval duration).

During clinical trials, daily administration of Alercys at doses up to 20 mg for 14 days was not associated with statistically or clinically significant cardiovascular changes. In a clinical-pharmacological study, administration of 45 mg/day (9 times higher than the therapeutic dose) for 10 days did not cause QT interval prolongation.

Desloratadine barely penetrates the blood-brain barrier. At the recommended dose of 5 mg, the incidence of somnolence did not exceed that in the placebo group. In clinical trials, Alercys did not affect psychomotor functions when administered at doses up to 7.5 mg.

In addition to the conventional classification of allergic rhinitis into seasonal and perennial forms, allergic rhinitis can alternatively be classified by symptom duration as intermittent or persistent. Intermittent allergic rhinitis is defined as symptoms occurring less than 4 days per week or for less than 4 weeks. Persistent allergic rhinitis is characterized by symptoms occurring 4 or more days per week or for more than 4 weeks.

The clinical efficacy of Alercys in the treatment of seasonal allergic rhinitis was demonstrated in four placebo-controlled clinical trials using multiple doses.

In patients with allergic rhinitis, Alercys effectively relieved symptoms such as sneezing, nasal discharge and itching, as well as eye irritation, tearing, redness, and itching of the palate.

Pharmacokinetics.

Desloratadine becomes detectable in plasma within 30 minutes after drug administration. Alercys effectively controls symptoms for 24 hours. Desloratadine is well absorbed. The maximum plasma concentration of desloratadine is reached on average within 3 hours; the elimination half-life averages 27 hours. The extent of desloratadine accumulation corresponds to its half-life (approximately 27 hours) and dosing frequency (once daily). The bioavailability of desloratadine was proportional to the dose in the range of 5 to 20 mg.

Desloratadine is moderately bound (83–87%) to plasma proteins. With administration of desloratadine at doses of 5 to 20 mg once daily for 14 days, no signs of clinically significant drug accumulation were observed.

A low rate of desloratadine metabolism was observed in approximately 8% of subjects, in whom a significant increase in plasma drug levels and prolonged elimination half-life were noted. The prevalence of slow metabolism may be influenced by race. This finding is currently considered clinically irrelevant.

Cross-comparative bioequivalence studies at the same dose have demonstrated bioequivalence between the tablet and syrup formulations of the drug.

Pharmacokinetic studies in pediatric practice have shown that AUC and Cmax values of desloratadine (when administered at recommended doses) are comparable to those in adults receiving desloratadine syrup at a dose of 5 mg.

Study results indicate that desloratadine does not inhibit CYP3A4 or CYP2D6 and is neither a substrate nor an inhibitor of P-glycoprotein.

Clinical characteristics.

Indications.

For relief of symptoms associated with allergic rhinitis, such as sneezing, nasal discharge, itching, swelling and nasal congestion, as well as eye itching and redness, tearing, itching of the palate, and cough.

For relief of symptoms associated with urticaria, such as itching and rash.

Contraindications.

Hypersensitivity to desloratadine, to any excipient of the medicinal product, or to loratadine.

Interaction with other medicinal products and other forms of interaction.

No clinically significant changes in plasma concentrations of desloratadine were observed during repeated co-administration with ketoconazole, erythromycin, azithromycin, fluoxetine, or cimetidine. Since the enzyme responsible for desloratadine metabolism has not been identified, interactions with other medicinal products cannot be completely excluded.

Food (high-fat, high-calorie meal) or grapefruit juice do not affect the distribution of desloratadine.

Effect on laboratory test results

Treatment with Alercis should be discontinued approximately 48 hours before skin testing, as antihistamines may prevent or reduce the manifestation of positive dermatological reactions to allergens.

Special precautions for use

During clinical pharmacological studies, Alersis did not enhance alcohol-induced effects such as psychomotor impairment and drowsiness. Results of psychomotor tests showed no significant differences between patients who took Alersis and those who received placebo, either alone or in combination with alcohol.

Alersis should be administered under medical supervision in patients with severe renal impairment. The medicinal product contains sorbitol and therefore should not be used in patients with hereditary fructose intolerance.

Desloratadine should be prescribed with caution in patients who have a history of seizures. Children may be more susceptible to developing a new seizure during desloratadine treatment. The physician must decide whether to discontinue desloratadine treatment in patients who experience a seizure while taking the drug.

Use during pregnancy or breastfeeding. Available data on the use of desloratadine during pregnancy (over 1000 cases) indicate no evidence of teratogenic or fetotoxic effects or adverse effects on the newborn. Studies in animals have not revealed any direct or indirect adverse effects on reproductive function. As a precautionary measure, it is advisable to avoid using the medicinal product Alersis during pregnancy.

Desloratadine is excreted into breast milk. Therefore, breastfeeding women should decide whether to discontinue breastfeeding or to avoid using the drug, taking into account the benefits of breastfeeding for the infant and the therapeutic benefits of the drug for the mother.

Fertility. Data on the effect on fertility are lacking.

Ability to affect reaction speed when driving or operating machinery.

Clinical study data indicate that Alersis has no effect or only a negligible effect on the ability to drive or operate machinery. Patients should be informed that most people do not experience drowsiness. Individual responses to medicinal products may vary. Patients are advised not to engage in activities requiring concentration, such as driving a car or operating machinery, until they have determined how they individually respond to the medicinal product.

Dosage and Administration.

To relieve symptoms associated with allergic rhinitis (including both intermittent and persistent forms) and urticaria, Alersis can be administered regardless of food intake in the following doses:

Adults and adolescents (≥ 12 years of age): 10 mL of syrup (5 mg of desloratadine) once daily.

Treatment of intermittent allergic rhinitis (symptoms present for less than 4 days per week or less than 4 weeks) should be guided by patient history: treatment should be discontinued upon symptom resolution and resumed upon symptom recurrence. For persistent allergic rhinitis (symptoms present for more than 4 days per week or more than 4 weeks), treatment should be continued throughout the entire period of allergen exposure.

Children. The efficacy and safety of Alersis solution in children under 6 months of age have not been established. The drug is not recommended for children under 6 months of age for the treatment of chronic idiopathic urticaria, or for children under 12 months of age for the treatment of allergic rhinitis. The following dosing regimen should be used:

• Children aged 6 to 11 months: 2 mL of solution (1 mg of desloratadine) once daily;
• Children aged 1 to 5 years: 2.5 mL of solution (1.25 mg of desloratadine) once daily;
• Children aged 6 to 11 years: 5 mL of solution (2.5 mg of desloratadine) once daily.

Overdose.

In case of overdose, standard measures aimed at removing the unabsorbed active substance should be taken, along with symptomatic treatment.

When desloratadine was administered at doses up to 45 mg (9 times the recommended dose) in clinical trials involving adults and adolescents, no clinically significant adverse effects were observed.

Desloratadine is not removed by hemodialysis; the possibility of its removal by peritoneal dialysis has not been established.

Adverse Reactions

During clinical trials for approved indications, including allergic rhinitis and chronic idiopathic urticaria, adverse events were reported in patients receiving a 5 mg daily dose 5% more frequently than in patients receiving placebo. The most commonly reported adverse reactions compared to placebo were fatigue (1.2%), dry mouth (0.8%), and headache (0.6%). During clinical trials of Alersis syrup in children aged 2 to 11 years, the incidence of adverse reactions was similar in both the syrup and placebo groups. In children aged 6 to 23 months, the most commonly reported adverse events (compared to placebo) were diarrhea (3.7%), fever (2.3%), and insomnia (2.3%).

There is a risk of psychomotor hyperactivity (abnormal behavior) associated with desloratadine use, which may manifest as irritability and aggression, as well as excitation.

In the post-marketing period, the following events have been observed (frequency unknown): QT interval prolongation, arrhythmias, and bradycardia.

Other adverse reactions reported very rarely during the post-marketing period are listed in the table below.

Other adverse reactions reported very rarely during the post-marketing period are listed in the table below. The frequency of adverse reactions is classified as follows: 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.

Desloratadine hardly penetrates into the central nervous system. When used at the recommended adult dose of 5 mg, no increase in the frequency of somnolence was observed compared with the placebo group. In clinical studies, the drug administered as a single daily dose of 7.5 mg had no effect on psychomotor performance.

Shelf life. 2 years.

Shelf life after first opening of the bottle – 48 days.

Storage conditions. Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of the reach of children.

Packaging. 60 ml of solution in a bottle with a measuring cup in a cardboard box.

Prescription status. Over-the-counter.

Manufacturer.

Laboratorios Normon S.A.

Manufacturer's address and site of operations.

Ronda de Valdecarrizo, 6, Tres Cantos, 28760 Madrid, Spain.