Elegius

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT ELEGIUS ELEHIUS

Composition:

Active substance: desloratadine;

1 tablet contains 5 mg of desloratadine;

Excipients: calcium hydrogen phosphate dihydrate, microcrystalline cellulose, corn starch, talc, film coating "Wincoat WT-AQ-1247 Blue" [hypromellose (hydroxypropylmethylcellulose), polyethylene glycol, titanium dioxide (E 171), talc, brilliant blue FCF (E 133)].

Pharmaceutical form. Film-coated tablets.

Main physicochemical characteristics: round, biconvex, film-coated tablets of blue color.

Pharmacotherapeutic group. Systemic antihistamines.

ATC code R06AX27.

Pharmacological Properties

Pharmacodynamics

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

In in vitro studies on endothelial cells, desloratadine demonstrated anti-allergic and anti-inflammatory properties. 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 by suppression of adhesion molecule expression, such as 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, desloratadine effectively relieved symptoms such as sneezing, rhinorrhea, nasal and ocular itching, tearing, redness, and palate itching. Desloratadine provided effective symptom control for 24 hours.

Desloratadine penetrates the central nervous system to a minimal extent. In controlled clinical trials, at the recommended dose of 5 mg daily, the incidence of somnolence was not different from that in the placebo group. In clinical studies, a single dose of desloratadine at 7.5 mg daily did not affect psychomotor performance.

Desloratadine effectively improves the course of seasonal allergic rhinitis, as evidenced by the total score of the rhinoconjunctivitis 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 conditions. Since histamine release is a causative factor in all forms of urticaria, desloratadine is expected to effectively relieve symptoms in other forms of urticaria, including chronic idiopathic urticaria.

In two placebo-controlled, 6-week studies involving patients with chronic idiopathic urticaria, desloratadine effectively reduced itching 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. Relief of itching by more than 50% was observed in 55% of patients taking desloratadine, compared to 19% of patients receiving placebo. The drug did not significantly affect sleep or daytime activity.

Pharmacokinetics

Absorption

Desloratadine plasma concentrations can be detected within 30 minutes after drug administration. Desloratadine is well absorbed, with peak concentrations reached approximately 3 hours after administration; 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. Desloratadine bioavailability was dose-proportional over 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. Maximum 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 was not different 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 of 5 to 20 mg once daily for 14 days.

Biotransformation

The enzyme responsible for desloratadine metabolism has not yet been identified; therefore, some interactions with other medicinal products cannot be completely excluded. 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 meal) 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. Use for the 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 noted when the medicinal product was used concomitantly with alcohol. However, during the post-marketing period, cases of alcohol intolerance and alcohol intoxication have been reported during use of the medicinal product. Therefore, caution should be exercised when consuming alcohol during treatment with desloratadine.

Special precautions for use

ELEGIUS should be administered under medical supervision in patients with severe renal impairment.

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

Use during pregnancy or breastfeeding

Pregnancy. Desloratadine did not show teratogenic effects in animal studies.

The safety of desloratadine use during pregnancy has not been established; therefore, the use of the medicinal product ELEGIUS during pregnancy is not recommended.

Breastfeeding. Desloratadine passes into breast milk; therefore, the use of the medicinal product ELEGIUS in breastfeeding women is not recommended.

Ability to affect reaction speed when driving or operating machinery

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

Dosage and Administration

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 less than 4 days per week or less than 4 weeks) should be based on patient history: discontinue after symptoms resolve and resume if symptoms reappear.

For persistent allergic rhinitis (symptoms present more than 4 days per week or more than 4 weeks), treatment should continue throughout the entire period of allergen exposure.

Children. Limited clinical data are available on the efficacy of desloratadine tablets in children aged 12 to 17 years (see section "Adverse Reactions").

The efficacy and safety of Elegius 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 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 evaluating the use of desloratadine for indications including allergic rhinitis and chronic idiopathic urticaria, the incidence of adverse events in patients receiving a 5 mg daily dose was 3% higher than in patients receiving placebo.

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

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

Use of desloratadine has been associated with a risk of psychomotor hyperactivity (abnormal behavior), which may manifest as irritability and aggression, as well as nervousness.

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

Summary table of adverse reactions

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.

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

Shelf life. 2 years.

Storage conditions

Store at a temperature not exceeding 25 °C.

Keep out of reach and sight of children.

Packaging. 10 tablets per blister; 1 blister per cardboard pack.

Supply classification. Over-the-counter.

Manufacturer/Marketing Authorization Holder. Ternopharm LLC.

Address of manufacturer and location of its operations / Address of the Marketing Authorization Holder

4 Fabrychna Street, Ternopil, 46010, Ukraine