ALERSIS

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

Composition:

Active substance: desloratadine;

1 tablet contains 5 mg of desloratadine;

Excipients: anhydrous lactose, microcrystalline cellulose, anhydrous calcium hydrogen phosphate, hydroxypropylcellulose, magnesium stearate, colloidal anhydrous silicon dioxide;

Tablet coating: hypromellose, titanium dioxide (E 171), talc, indigo carmine (E 132), macrogol 600.

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: blue-colored, biconvex, round-shaped film-coated tablets.

Pharmacotherapeutic group. Antihistamines for systemic use.

ATC code R06A X27.

Pharmacological Properties.

Pharmacodynamics.

Desloratadine is a non-sedating, long-acting antihistamine with selective antagonistic activity at peripheral H1-receptors. After oral administration, desloratadine selectively blocks peripheral histamine H1-receptors.

In in vitro studies, desloratadine has demonstrated anti-allergic and anti-inflammatory properties on endothelial cells. This was manifested by inhibition of pro-inflammatory cytokine release, such as IL-4, IL-6, IL-8, and IL-13, from human mast cells/basophils, as well as suppression of adhesion molecule expression, including P-selectin. The clinical significance of these observations has yet to be confirmed.

In high-dose clinical studies where desloratadine was administered daily at doses up to 20 mg for 14 days, no statistically significant cardiovascular effects were observed. In a clinical pharmacology study using a daily dose of 45 mg (10 times the maximum recommended clinical daily dose) for 10 days, no QT interval prolongation was observed.

In patients with allergic rhinitis, Alersys effectively relieved symptoms such as sneezing, rhinorrhea, nasal pruritus, as well as ocular irritation, lacrimation, redness, and palatal itching. Alersys provided effective symptom control for 24 hours.

Desloratadine barely penetrates the central nervous system. In controlled clinical trials, at the recommended daily dose of 5 mg, the incidence of somnolence was not different from placebo. In clinical studies, a single dose of Alersys at 7.5 mg per day did not affect psychomotor performance.

Alersys effectively reduced the severity of seasonal allergic rhinitis, as measured by the total score of the rhino-conjunctivitis quality of life questionnaire. The greatest improvement was observed in questionnaire items related to practical problems and daily activities limited by symptoms.

Chronic idiopathic urticaria was studied in a clinical model of urticaria. Since histamine release is a causative factor in all forms of urticaria, desloratadine is expected to effectively relieve symptoms in other forms of urticaria besides chronic idiopathic urticaria.

In two placebo-controlled, 6-week studies involving patients with chronic idiopathic urticaria, Alersys effectively reduced pruritus and decreased the number and size of hives by the end of the first dosing interval. In each study, the effect lasted throughout the 24-hour dosing interval. A reduction in pruritus by more than 50% was observed in 55% of patients taking desloratadine, compared to 19% of patients taking placebo. The drug did not significantly affect sleep or daytime activity.

Pharmacokinetics.

Absorption.

Desloratadine plasma concentrations can be detected within 30 minutes after administration. Desloratadine is well absorbed, with peak concentrations reached approximately 3 hours after intake; the elimination half-life is approximately 27 hours. The extent of desloratadine accumulation corresponds to its half-life (approximately 27 hours) and once-daily dosing regimen. Desloratadine bioavailability was dose-proportional in the range of 5 to 20 mg.

In a pharmacokinetic study where patient demographics were comparable to the general population with seasonal allergic rhinitis, approximately 4% of participants showed higher desloratadine concentrations. This proportion may vary depending on ethnicity. Peak desloratadine concentration was approximately 3 times higher at about 7 hours, and the terminal half-life was approximately 89 hours. The safety profile in these patients did not differ from that in the general population.

Distribution.

Desloratadine is moderately bound to plasma proteins (83–87%). No evidence of clinically significant accumulation was observed after administration of desloratadine doses (5 to 20 mg) once daily for 14 days.

Biotransformation.

The enzyme responsible for desloratadine metabolism has not yet been identified; therefore, some potential for interaction with other medicinal products cannot be completely ruled out. Desloratadine does not inhibit CYP3A4 in vivo. In vitro studies have shown that the drug does not inhibit CYP2D6, nor is it a substrate or inhibitor of P-glycoprotein.

Elimination.

In a single-dose study of 7.5 mg desloratadine, food intake (a high-fat, high-calorie breakfast) did not affect the pharmacokinetics of desloratadine. It has also been established that grapefruit juice does not affect the pharmacokinetics of desloratadine.

Clinical characteristics.

Indications.

Relief of symptoms associated with:

• allergic rhinitis (see section "Pharmacological properties");
• urticaria (see section "Pharmacological properties").

Contraindications.

Hypersensitivity to the active substance or to any of the excipients of the medicinal product or to loratadine.

Interaction with other medicinal products and other forms of interaction.

In clinical studies of desloratadine tablets, no clinically significant interactions were observed when co-administered with erythromycin or ketoconazole.

In clinical pharmacological studies, no enhancement of the negative effect of ethanol on psychomotor function was observed when the drug was used concomitantly with alcohol. However, during the post-marketing period, cases of alcohol intolerance and alcohol intoxication during the use of the drug were reported. Therefore, caution should be exercised when consuming alcohol during treatment with Alersys.

Special precautions for use.

In patients with severe renal impairment, the use of Alersis should be carried out under medical supervision.

Patients with rare hereditary conditions of galactose intolerance, lactase deficiency, or glucose-galactose malabsorption should not take this medication.

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

Use during pregnancy or breastfeeding.

Desloratadine did not show teratogenic effects in animal studies.

The safety of using the drug during pregnancy has not been established. Therefore, the use of Alersis during pregnancy is not recommended.

Breastfeeding period.

Desloratadine is excreted in breast milk; therefore, the use of Alersis in breastfeeding women is not recommended.

Ability to influence reaction speed when driving or operating machinery.

In clinical studies assessing the ability to drive, no impairment was observed in patients taking desloratadine. Nevertheless, patients should be informed that in individual cases, some people may experience drowsiness, which could affect their ability to drive or operate complex machinery.

Method of Administration and Dosage.

For adults and children aged 12 years and older: 1 tablet once daily, regardless of food intake, to relieve symptoms associated with allergic rhinitis (including intermittent and persistent allergic rhinitis) and urticaria.

Treatment of intermittent allergic rhinitis (symptoms present for less than 4 days per week or less than 4 weeks) should be based on patient history: discontinue after symptoms resolve and resume upon their 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.

There are limited clinical data on the efficacy of desloratadine tablets in adolescents aged 12 to 17 years (see section "Adverse Reactions").

The efficacy and safety of Alercis tablets in children under 12 years of age have not been established.

Overdose.

In case of overdose, standard measures should be applied to remove the unabsorbed active substance. Symptomatic and supportive therapy is recommended. In clinical studies where desloratadine was administered at doses of 45 mg (9 times higher than the recommended dose), no clinically significant adverse reactions were observed. Desloratadine is not removed by hemodialysis; the possibility of its removal by peritoneal dialysis has not been established.

Adverse Reactions

In clinical trials for the approved indications, including allergic rhinitis and chronic idiopathic urticaria, adverse events were reported 3% more frequently in patients receiving a 5 mg daily dose compared to those receiving placebo.

The most commonly reported adverse reactions compared to placebo were fatigue (1.2%), dry mouth (0.8%), and headache (0.6%).

Children. In clinical trials involving 578 adolescents aged 12 to 17 years, the most commonly reported adverse reaction was headache, occurring in 5.9% of patients taking desloratadine and 6.9% of patients receiving placebo.

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

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

Summary table of adverse reaction frequencies.

The frequency of adverse reactions is classified according to the following criteria: 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 frequency not known (cannot be estimated from available data).

Shelf life. 2 years.

Storage conditions. Store in the original packaging at a temperature not exceeding 25 °C. Keep out of reach of children.

Packaging. 10 tablets in a blister pack, 1 blister pack in a cardboard box.

Availability. Over-the-counter (without prescription).

Manufacturer. Laboratorios Normon S.A.

Manufacturer's address and place of business. Ronda de Valdecarrizo, 6, Tres Cantos, 28760 Madrid, Spain.