Eridess®

INSTRUCTION for medical use of the medicinal product Eridez® Eridez®

Composition:

active substance: desloratadine;

1 ml of syrup contains desloratadine 0.5 mg;

excipients: propylene glycol, sorbitol liquid non-crystallizing, citric acid monohydrate, sodium citrate, sucrose, sodium benzoate (E 211), disodium edetate, banana flavor, purified water.

Pharmaceutical form. Syrup.

Main physicochemical properties: clear yellowish liquid.

Pharmacotherapeutic group. Antihistamines for systemic use.

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, the medicinal product Erius® selectively blocks peripheral H1-histamine receptors, as it barely penetrates the blood-brain barrier.

Numerous studies have shown that in addition to antihistaminic activity, desloratadine possesses anti-allergic and anti-inflammatory properties. It has been established that the medicinal product Erius® 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 desloratadine use in children has been demonstrated in three clinical trials. The medicinal product was administered to children aged 6 months to 11 years who required 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 desloratadine at doses up to 20 mg for 14 days was not associated with statistically significant clinically relevant changes in the cardiovascular system. In a clinical-pharmacological study, administration of desloratadine at 45 mg per 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, desloratadine 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, it may alternatively be classified according to symptom duration as intermittent or persistent. Intermittent allergic rhinitis is defined by symptoms occurring for less than 4 days per week or less than 4 weeks. Persistent allergic rhinitis is characterized by symptoms occurring for 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 dosing regimens.

In patients with allergic rhinitis, desloratadine effectively relieves symptoms such as sneezing, nasal discharge and itching, as well as eye irritation, lacrimation, redness, and itching of the palate.

Pharmacokinetics.

Desloratadine becomes detectable in plasma within 30 minutes after administration and effectively controls symptoms for 24 hours. Desloratadine is well absorbed. The maximum plasma concentration of desloratadine (Cmax) 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 dose-proportional in the range of 5 mg 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 from 5 mg to 20 mg once daily for 14 days.

A low rate of desloratadine metabolism has been observed in approximately 8% of patients, in whom a significant increase in plasma desloratadine 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-comparative bioequivalence studies at the same dosage have 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 observed 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 redness and itching, tearing, itching of the palate, and cough.

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

Contraindications.

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

Interaction with other medicinal products and other types of interactions.

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 desloratadine distribution.

Effect on laboratory test results

Treatment with the medicinal product Eridez® should be discontinued approximately 48 hours before skin testing, as antihistamine medicinal products 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 showed no significant differences between patients receiving desloratadine and those receiving placebo, either alone or in combination with alcohol.

Erydes® 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 during treatment with desloratadine. Physicians should consider discontinuing desloratadine in patients who experience a seizure while on the medication.

Important information about excipients.

The medicinal product contains sorbitol, which may have a mild laxative effect. The energy value of 1 g of sorbitol is 2.6 kcal. The medicinal product Erydes® contains 49 g of sucrose per 100 ml; therefore, it should be used with caution in patients with diabetes mellitus.

Use during pregnancy or breastfeeding.

Extensive 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 Erydes® 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 affect reaction speed when driving or operating machinery.

Clinical study 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 individuals do not experience drowsiness. However, individual responses to medications may vary. Patients should refrain from activities requiring concentration, such as driving a car or operating machinery, until they have determined their individual response to the medicinal product.

Dosage and Administration

To relieve symptoms associated with allergic rhinitis (including intermittent and persistent forms) and urticaria, the medicinal product Erius® can be taken 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 initiated 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 continue throughout the entire period of allergen exposure.

Children

The efficacy and safety of Erius® syrup in children under 6 months of age have not been established. The medicinal product is not recommended for children under 6 months of age for the treatment of chronic idiopathic urticaria and for children under 12 months of age for the treatment of allergic rhinitis. The following dosing regimen should be used for treatment:

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

Overdose

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

In clinical studies, administration of desloratadine at doses up to 45 mg (9 times higher than the recommended dose) in adults and adolescents 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 studies for indications including allergic rhinitis and chronic idiopathic urticaria, adverse reactions were reported in patients receiving a 5 mg daily dose 3% 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 Eridez® 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 frequently reported adverse reactions (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, arrhythmia, and bradycardia.

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 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), frequency not known (cannot be estimated from available data).

Eye disorders: frequency not known – dry eyes.

Gastrointestinal disorders: common – dry mouth; common (in children under 2 years of age) – diarrhea; rare – abdominal pain, nausea, vomiting, dyspepsia, diarrhea.

Hepatobiliary disorders: rare – increased liver enzymes, elevated bilirubin, hepatitis; frequency not known – jaundice.

Metabolism and nutrition disorders: frequency not known – increased appetite.

Nervous system disorders: common – headache; common (in children under 2 years of age) – insomnia; rare – dizziness, somnolence, insomnia, psychomotor hyperactivity, convulsions.

Psychiatric disorders: rare – hallucinations; frequency not known – abnormal behavior, aggression.

Cardiac disorders: rare – tachycardia, palpitations, QT interval prolongation, supraventricular tachyarrhythmia.

Skin and subcutaneous tissue disorders: frequency not known – photosensitivity.

Musculoskeletal and connective tissue disorders: rare – myalgia.

General disorders and administration site conditions: common – fatigue; common (in children under 2 years of age) – fever; rare – hypersensitivity reactions (anaphylaxis, Quincke's edema, dyspnea, pruritus, rash, urticaria); frequency not known – asthenia.

Investigations: frequency not known – weight gain.

Desloratadine penetrates the central nervous system to a minimal extent. When administered at the recommended adult dose of 5 mg, no increase in somnolence was observed compared to the placebo group. In clinical trials, Eridez® at a single daily dose of 7.5 mg did not affect psychomotor performance.

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after medicine registration is important. It allows continuous monitoring of the benefit-risk balance of the medicine. Healthcare and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and/or lack of efficacy through the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.

Shelf life. 2 years.

After first opening the bottle, do not store for more than 90 days.

Storage conditions.

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

Packaging. 100 ml in a bottle closed with a tamper-evident cap, 1 bottle with a measuring cup in a carton.

Dispensing category. Over-the-counter.

Manufacturer. JSC "Pharmaceutical Company "Darnytsia".

Manufacturer's address and location of its business activities.

13, Borispilska Street, Kyiv, 02093, Ukraine.