Erius

INSTRUCTION for medical use of the medicinal product ERIUSâ AERIUSâ

Composition:

Active substance: desloratadine;

1 ml of syrup contains 0.5 mg of desloratadine;

Excipients: propylene glycol, sorbitol solution non-crystallizing, citric acid anhydrous, sodium citrate dihydrate, sodium benzoate (E 211), disodium edetate, sucrose, natural and artificial flavor with a bubble gum taste (No. 15864), FD&C Yellow No. 6 (E 110), purified water.

Pharmaceutical form. Syrup.

Main physicochemical properties: clear orange-colored liquid.

Pharmacotherapeutic group. Antihistamines for systemic use.

ATC code R06A X27.

Pharmacological Properties

Pharmacodynamics

Desloratadine is a potent, selective blocker of peripheral histamine H1 receptors and does not exhibit sedative effects. Desloratadine is the principal active metabolite of loratadine.

After oral administration, ERYS® selectively blocks peripheral H1 histamine receptors, as the drug barely penetrates the blood-brain barrier.

Numerous studies have demonstrated that, in addition to its antihistaminic activity, ERYS® exhibits anti-allergic and anti-inflammatory properties. It has been established that ERYS® suppresses a 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;
• superoxide anion production by activated polymorphonuclear neutrophils;
• eosinophil adhesion and chemotaxis;
• expression of adhesion molecules, such as P-selectin;
• IgE-dependent release of histamine, prostaglandin D2, and leukotriene C4;
• acute allergic bronchospasm and allergic cough, as observed in animal studies.

The safety of ERYS® in children has been demonstrated in three clinical trials. The drug 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 monitoring, and ECG data (including QT interval duration).

During clinical trials, daily administration of ERYS® at doses up to 20 mg for 14 days was not associated with statistically or clinically significant cardiovascular changes. In a clinical pharmacology study, administration of ERYS® 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 somnolence did not exceed that observed in the placebo group. In clinical trials, ERYS® 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 may 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 for 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 ERYS® in the treatment of seasonal allergic rhinitis has been demonstrated in four placebo-controlled clinical trials using multiple doses.

In patients with allergic rhinitis, ERYS® effectively relieved symptoms such as sneezing, rhinorrhea, nasal itching, as well as eye irritation, lacrimation, redness, and palatal itching.

Pharmacokinetics

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

Desloratadine is moderately bound (83–87%) to plasma proteins. No evidence of clinically significant drug accumulation was 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 significantly increased plasma levels and prolonged elimination half-life were noted. The prevalence of slow metabolism may be influenced by race. This is currently considered clinically irrelevant.

Cross-over comparative studies at equivalent doses demonstrated bioequivalence between the tablet and syrup formulations.

Pharmacokinetic studies in pediatric practice showed that AUC and Cmax values of desloratadine (when administered at recommended doses) are comparable to those in adults receiving desloratadine syrup at a 5 mg dose.

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, nasal swelling and congestion, as well as eye redness and itching, lacrimation, itching of the palate, and cough.

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

Contraindications.

Hypersensitivity to desloratadine, to any excipient of the drug, 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 ruled out.

Food (high-fat, high-calorie meal) or grapefruit juice do not affect desloratadine distribution.

Effect on laboratory test results

Treatment with Erius® should be discontinued approximately 48 hours before performing skin tests, as antihistamines may prevent or reduce the manifestation of positive dermatological reactions to allergens.

Special precautions for use.

During clinical pharmacological studies, Erius® did not enhance alcohol-induced effects such as impairment of psychomotor function and drowsiness. Results of psychomotor tests showed no significant differences between patients who received Erius® and those who received placebo, either alone or in combination with alcohol.

Erius® should be administered under medical supervision in patients with severe renal impairment. The medicinal product contains sorbitol and therefore should not be used in patients with hereditary fructose intolerance.

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

Use during pregnancy or breast-feeding. Extensive data on the use of desloratadine during pregnancy (over 1000 cases) indicate no teratogenic, fetotoxic effects or adverse effects on the newborn. Studies in animals have not shown any direct or indirect adverse effects on reproductive function. As a precautionary measure, it is advisable to avoid using Erius® during pregnancy.

Desloratadine passes into breast milk; therefore, breastfeeding women should decide whether to discontinue breastfeeding or 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 effects on fertility are lacking.

Ability to influence reaction rate when driving or operating machinery.

Clinical trial data indicate that Erius® 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. Individual responses to medicinal products may vary. Patients are advised not to engage in 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, Erius® syrup can be taken regardless of food intake, in the following doses:

Adults and adolescents (≥12 years of age): 10 mL of syrup (5 mg desloratadine) once daily.

Treatment of intermittent allergic rhinitis (symptoms present 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 more than 4 days per week or longer 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 drug is not recommended for children under 6 months of age for the treatment of chronic idiopathic urticaria, or 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 desloratadine) once daily;
• Children aged 1 to 5 years: 2.5 mL of syrup (1.25 mg desloratadine) once daily;
• Children aged 6 to 11 years: 5 mL of syrup (2.5 mg desloratadine) once daily.

Overdose

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

In clinical trials, administration of desloratadine at doses up to 45 mg (9 times the recommended dose) in adults and adolescents did not result in clinically significant effects.

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

Adverse Reactions

During clinical trials for approved 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 reactions compared to placebo were fatigue (1.2%), dry mouth (0.8%), and headache (0.6%). During clinical trials of Erius® 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 postmarketing period, the following events have been observed (frequency unknown): QT interval prolongation, arrhythmias, and bradycardia.

Other adverse reactions reported very rarely during the postmarketing 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 frequency of drowsiness was observed compared to the placebo group. In clinical studies, Erius® administered as a single daily dose of 7.5 mg did not affect psychomotor performance.

Shelf life. 2 years.

Storage conditions. Store out of reach of children at a temperature not exceeding 30 °C.

Packaging. Bottles of 60 ml or 120 ml, closed with a tamper-evident cap with child-resistant closure, supplied with a measuring spoon or dosing syringe, in a cardboard box.

Prescription status. Over-the-counter.

Manufacturer.

Organon Heist B.V. /
Organon Heist B.V.

Manufacturer's address and place of business.
Industriepark 30, Heist-op-den-Berg, 2220, Belgium /
Industriepark 30, Heist-op-den-Berg, 2220, Belgium.