Elizieum

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ELEZIUM (ELIZIUM)

Composition:

Active ingredient: desloratadine;

One film-coated tablet contains 5 mg of desloratadine;

Excipients: microcrystalline cellulose, corn starch, mannite (E 421), talc, magnesium stearate;

Film-coating composition: Opadry Blue 03F20404 (hypromellose, titanium dioxide (E 171), polyethylene glycol (macrogol), indigo carmine aluminum lake (E 132)).

Pharmaceutical form. Film-coated tablets.

Main physicochemical characteristics: blue, round, biconvex film-coated tablets with "LT" imprint on one side.

Pharmacotherapeutic group. Systemic antihistamines.

ATC code R06A X27.

Pharmacological Properties

Pharmacodynamics

Desloratadine is a non-sedating, long-acting antihistamine that exerts a selective antagonistic effect on peripheral H1 receptors. After oral administration, desloratadine selectively blocks peripheral histamine H1 receptors.

In in vitro studies, desloratadine demonstrated anti-allergic and anti-inflammatory properties on endothelial cells. This was manifested by inhibition of the release of pro-inflammatory cytokines such as IL-4, IL-6, IL-8, and IL-13 from human basophils/mast cells, as well as suppression of expression of adhesion molecules such as P-selectin. The clinical significance of these observations requires further confirmation.

In high-dose clinical studies, in which 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, administration of 45 mg of desloratadine per day (10 times the maximum daily clinical dose) for 10 days did not result in QT interval prolongation.

Desloratadine penetrates the central nervous system to a minimal extent. In controlled clinical trials, at the recommended dose of 5 mg per day, 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 did not affect psychomotor performance.

In patients with allergic rhinitis, desloratadine effectively relieved symptoms such as sneezing, rhinorrhea, nasal and ocular pruritus, tearing, redness, and palate itching. Desloratadine provided effective symptom control for 24 hours.

The efficacy of desloratadine tablets in children aged 12–17 years has not been definitively demonstrated in clinical trials.

Desloratadine effectively improved the severity of seasonal allergic rhinitis, as measured 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. Since histamine release is a causative factor in all forms of urticaria, desloratadine is expected to effectively relieve symptoms in other forms of urticaria as well.

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 receiving desloratadine compared to 19% of patients receiving placebo. Treatment with desloratadine also significantly reduced the impact of the disease on sleep and daytime activity, as measured by a four-point scale used to assess these changes.

Pharmacokinetics

Absorption. Desloratadine plasma concentrations can be detected within 30 minutes after administration. Desloratadine is well absorbed, with peak plasma concentration (Cmax) reached approximately 3 hours after intake; the elimination half-life (T½) is approximately 27 hours. The extent of desloratadine accumulation corresponds to its T½ (approximately 27 hours) and a dosing frequency of once daily. 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, 4% of participants showed higher desloratadine concentrations. This proportion may vary depending on ethnic background. Cmax of desloratadine was approximately 3 times higher at about 7 hours, and the terminal T½ 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.

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

Excretion. 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. Grapefruit juice also had no effect on desloratadine pharmacokinetics.

Patients with renal impairment. The pharmacokinetics of desloratadine in patients with chronic renal insufficiency were compared to those in healthy subjects in one single-dose and one multiple-dose study. In both studies, changes in exposure (AUC and Cmax) of desloratadine and 3-hydroxydesloratadine were not clinically significant.

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 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 have been reported during treatment with the drug. Therefore, caution should be exercised when consuming alcohol during desloratadine therapy.

Interaction studies were conducted only in adult patients.

Special precautions for use

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

Desloratadine should be prescribed with caution to patients who have a history of seizures. Children may be more susceptible to developing a new seizure during treatment with desloratadine. Physicians should consider discontinuing desloratadine in patients who experience a seizure while taking the medication.

Use during pregnancy or breastfeeding

Pregnancy. A large amount of data from use in pregnant women (over 1,000 completed pregnancies) does not indicate any teratogenic or fetal/neonatal toxicity associated with desloratadine. Animal studies have not revealed any direct or indirect adverse effects related to reproductive toxicity. As a precautionary measure, desloratadine should not be used during pregnancy.

Breastfeeding. Desloratadine has been detected in the bodies of newborns/infants who were breastfed by women taking this medication. The effects of desloratadine on newborns/infants are unknown. Women who are breastfeeding are advised to decide whether to discontinue breastfeeding or avoid using the medication, taking into account the benefits of breastfeeding for the child and the therapeutic benefits of the drug for the mother.

Fertility. There are no data available regarding the effect of the drug on fertility in men or women.

Ability to affect reaction speed when driving or operating machinery

According to clinical trials, desloratadine has no effect or only a negligible effect on the ability to drive vehicles or operate machinery. Patients should be informed that somnolence may occur very rarely. Due to individual responses to medications, it is recommended that patients avoid activities requiring mental alertness, such as driving vehicles or operating machinery, until they have determined their individual response to the medication.

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 upon their recurrence.

For persistent allergic rhinitis (symptoms present 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 children aged 12 to 17 years (see section "Adverse Reactions").

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

Overdose

According to post-marketing data, the adverse reaction profile associated with overdose was similar to that of therapeutic doses, but the manifestations were more severe.

Treatment. In case of overdose, standard measures aimed at removing unabsorbed active substance should be applied, along with symptomatic and supportive treatment. Desloratadine is not removed by hemodialysis; the possibility of its removal by peritoneal dialysis has not been established.

Symptoms. In clinical trials of multiple dosing of desloratadine up to 45 mg (9 times higher than the therapeutic dose), no clinically significant effects were observed.

Children. According to post-marketing experience, the adverse reaction profile associated with overdose is similar to that observed with therapeutic doses; however, the manifestations may be more severe.

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 the 5 mg daily dose compared to patients receiving placebo.

The most commonly reported adverse events 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, occurring in 5.9% of patients taking desloratadine and in 6.9% of patients receiving placebo.

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

Summary table of adverse reaction frequencies.

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.

Children. During the post-marketing period, other adverse reactions (frequency unknown) have been reported: QT interval prolongation, arrhythmia, bradycardia, behavioral disturbances, and aggression.

A retrospective observational safety study revealed an increased incidence of seizures occurring in patients aged 0 to 19 years during desloratadine use compared to periods when they were not taking desloratadine.

In children aged 0–4 years, the adjusted absolute increase was 37.5 (95% confidence interval [CI] 10.5–64.5) per 100,000 person-years, with a background seizure incidence rate of 80.3 per 100,000 person-years. In patients aged 5–19 years, the adjusted absolute increase was 11.3 (95% CI 2.3–20.2) per 100,000 person-years, with a background rate of 36.4 per 100,000 person-years.

Suspected adverse reactions reporting

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

Shelf life. 3 years.

Storage conditions

Store at a temperature not exceeding 25 °C. Keep out of reach of children.

Packaging

10 film-coated tablets in a blister. 1 or 3 blisters per cardboard box.

Prescription status

Over-the-counter.

Manufacturer

Actavis Ltd.

Manufacturer’s address and place of business

BLB 015, BLB 016, Bulbula Industrial Estate, Zejtun, ZTN 3000, Malta.

Marketing Authorization Holder

SPERCO INTERNATIONAL LIMITED.

Address of the Marketing Authorization Holder

Spyrou Kyprianou, 57, Bibleserv Business Center, 2nd floor, 6051 Larnaca, Cyprus.