Elegius

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT ELEGIUS (ELEHIUS)

Composition:

Active substance: desloratadine;

1 ml of syrup contains 0.5 mg of desloratadine;

Excipients: propylene glycol; sorbitol (E 420); citric acid monohydrate; sodium citrate; sodium benzoate (E 211); disodium edetate; sucrose; colouring agent "Yellow Sunset FCF" (E 110); purified water.

Pharmaceutical form. Syrup.

Main physicochemical properties: clear orange-coloured liquid.

Pharmacotherapeutic group. Systemic antihistamines.

ATC code R06AX27.

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, desloratadine 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, desloratadine possesses anti-allergic and anti-inflammatory properties. It has been established that desloratadine suppresses the cascade of various reactions underlying allergic inflammation, namely:

• release of pro-inflammatory cytokines, including IL-4, IL-6, IL-8, IL-13;
• release of pro-inflammatory 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 desloratadine use in children has been demonstrated in three clinical trials. The drug was administered to children aged 1 to 11 years requiring antihistamine therapy at a daily dose of 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 desloratadine 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 desloratadine at 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 drowsiness did not exceed that in the placebo group. In clinical trials, desloratadine did not affect psychomotor performance 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 according to symptom duration as intermittent or persistent. Intermittent allergic rhinitis is defined as symptoms occurring less than 4 days per week or 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 desloratadine in the treatment of seasonal allergic rhinitis has been demonstrated in four placebo-controlled clinical trials using multiple doses.

In patients with allergic rhinitis, desloratadine effectively relieved symptoms such as sneezing, rhinorrhea, nasal itching, as well as ocular irritation, tearing, redness, and palatal itching.

Pharmacokinetics

Desloratadine becomes detectable in plasma within 30 minutes after drug administration. Desloratadine effectively controls symptoms for 24 hours. Desloratadine is well absorbed. 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 frequency of administration (once daily). The bioavailability of desloratadine was proportional to the dose in the range of 5 to 20 mg.

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

A low rate of desloratadine metabolism has been 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 factor is currently considered clinically irrelevant.

Cross-over comparative studies at the same dosage demonstrated bioequivalence between the tablet and syrup formulations.

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

The medicinal product Elegius is indicated for use in adults and children from 1 year of age for reduction of symptoms associated with:

• allergic rhinitis (sneezing, nasal discharge, itching, nasal swelling and congestion, eye itching and redness, lacrimation, itching of the palate area, and cough);
• urticaria (itching, 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 breakfast) or grapefruit juice do not affect the distribution of desloratadine.

Effect on laboratory test results

Desloratadine 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, desloratadine did not enhance alcohol-induced effects such as psychomotor impairment and drowsiness. Results of psychomotor performance tests did not differ significantly between patients receiving desloratadine and those receiving placebo, either alone or in combination with alcohol.

Desloratadine should be administered under medical supervision in patients with severe renal impairment. Desloratadine should be used with caution in patients with a history of seizures. Children may be more susceptible to developing a new seizure episode during treatment with desloratadine. Physicians should consider discontinuing desloratadine in patients who experience a seizure while taking the medication.

The medicinal product contains sorbitol and therefore should not be used in patients with hereditary fructose intolerance.

The product contains propylene glycol, which may produce symptoms similar to those caused by alcohol consumption.

The medicinal product contains sucrose, which may have adverse effects on teeth.

The product also contains the dye "Yellow FCF", which may cause allergic reactions.

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. Animal studies 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 Elegius during pregnancy.

Desloratadine passes into breast milk; therefore, breastfeeding women should decide whether to discontinue breastfeeding or to avoid using the medicinal product, taking into account the benefits of breastfeeding for the child and the therapeutic benefits of the drug for the mother.

Fertility. Data on the effect on fertility are lacking.

Ability to influence reaction speed when driving or operating machinery

Clinical trial data indicate that desloratadine 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, but individual responses to the medicinal product may vary. Patients are advised not to engage in activities requiring mental alertness, such as driving a car or operating machinery, until they have determined how they react to the medication.

Dosage and Administration

To relieve symptoms associated with allergic rhinitis (including intermittent and persistent forms) and urticaria, Elegius should be taken regardless of food intake, in the following doses:

Adults and children aged 12 years and older: 10 mL of syrup (5 mg of desloratadine) once daily.

Treatment of intermittent allergic rhinitis (symptoms present less than 4 days per week or for less than 4 weeks) should be based on patient history: treatment should be discontinued after symptoms resolve and resumed upon their recurrence. For persistent allergic rhinitis (symptoms present more than 4 days per week or for more than 4 weeks), treatment should continue throughout the entire period of allergen exposure.

Children

The efficacy and safety of the syrup in children under 1 year of age have not been established. The medicinal product is not recommended for children under 1 year of age for the treatment of chronic idiopathic urticaria or allergic rhinitis. The following dosing regimen should be used for treatment:

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

Overdose

In case of overdose, standard measures should be taken to remove the unabsorbed active substance, along with symptomatic treatment.

During clinical trials, administration of desloratadine at doses up to 45 mg (9 times the recommended dose) in adults and children aged 12 years and older did not result in clinically significant effects.

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

Adverse Reactions

During clinical trials for indications including allergic rhinitis and chronic idiopathic urticaria, adverse events were reported in patients receiving a 5 mg daily dose 3% more frequently than in patients receiving placebo. The most commonly reported adverse events compared to placebo were: fatigue (1.2%), dry mouth (0.8%), and headache (0.6%). In clinical trials of desloratadine in children aged 2 to 11 years, the incidence of adverse reactions was similar in both the syrup treatment group and the placebo group. 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, very rarely reported 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 frequency not known.

Desloratadine hardly penetrates into the central nervous system. When used at the recommended adult dose of 5 mg, no increase in the incidence of somnolence was observed compared to the placebo group. In clinical studies, desloratadine at a single daily dose of 7.5 mg did not affect psychomotor performance.

Reporting of adverse reactions after drug registration is of great importance. It enables ongoing monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, are encouraged to report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Shelf life after opening the bottle — 90 days.

Storage conditions

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

Keep out of reach of children.

Packaging

60 ml or 100 ml in bottles with a measuring spoon, 1 bottle in a cardboard box.

Supply classification. Over-the-counter (without prescription).

Manufacturer/Marketing Authorization Holder

LLC "Ternofarm".

Manufacturer's address / Marketing Authorization Holder's address

4 Fabrychna Street, Ternopil, 46010, Ukraine.