Edem

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT EDEM® (EDEM)

Composition:

Active substance: desloratadine;

1 ml of syrup contains desloratadine equivalent to 100% substance 0.5 mg;

Excipients: sorbitol (E 420); sucrose; sodium hydrogen phosphate dodecahydrate; sodium benzoate (E 211); disodium edetate; propylene glycol; citric acid monohydrate; yellow azo dye FCF (E 110); purified water.

Pharmaceutical form. Syrup.

Main physicochemical properties: clear, viscous, orange-colored liquid.

Pharmacotherapeutic group.

Antihistamines for systemic use.

ATC code R06AX27.

Pharmacological Properties

Pharmacodynamics

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

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

Numerous studies have demonstrated that in addition to its antihistaminic activity, Edem® exhibits anti-allergic and anti-inflammatory properties. It has been shown that Edem® suppresses a 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, as observed in animal studies.

The safety of Edem® in children has been demonstrated in three clinical trials. The drug was administered to children aged 6 months to 11 years requiring antihistamine therapy at daily doses of 1 mg (age group 6–11 months), 1.25 mg (age group 1–5 years), or 2.5 mg (age group 6–11 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 Edem® at doses up to 20 mg for 14 days was not associated with statistically or clinically significant cardiovascular effects. In a clinical pharmacology study, administration of Edem® at 45 mg/day (9 times the therapeutic dose) for 10 days did not result in QT interval prolongation.

Desloratadine poorly 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, Edem® 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 by symptom duration as intermittent or persistent. Intermittent allergic rhinitis is defined as symptoms occurring for less than 4 days per week or for 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 Edem® 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, Edem® effectively relieved symptoms such as sneezing, rhinorrhea, nasal and ocular itching, lacrimation, eye redness, and palatal itching.

Pharmacokinetics

Desloratadine is detectable in plasma within 30 minutes after administration. Edem® effectively controls symptoms for 24 hours. Desloratadine is well absorbed. Peak plasma concentration (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 the dosing frequency (once daily). Desloratadine bioavailability is 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 reduced rate of desloratadine metabolism has been observed in approximately 8% of subjects, who showed significantly increased plasma levels and prolonged elimination half-life. The prevalence of this metabolic impairment may be influenced by race. However, this is considered clinically irrelevant.

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

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 5 mg of desloratadine syrup.

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, runny nose, itching, nasal swelling and congestion, as well as itchy and red eyes, tearing, 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 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 meal) or grapefruit juice do not affect desloratadine distribution.

Effect on laboratory test results

Treatment with Edem® 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, Edem® did not enhance alcohol effects such as psychomotor impairment and drowsiness. Psychomotor test results did not significantly differ between patients who received Edem® and those who received placebo, either alone or in combination with alcohol.

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

The product contains sodium compounds, which should be taken into account in patients on a controlled sodium diet.

Use during pregnancy or breastfeeding.

The safety of Edem® use during pregnancy has not been established; therefore, its use during pregnancy is not recommended.

Desloratadine passes into breast milk; therefore, Edem® is not recommended for use in breastfeeding women.

Ability to affect reaction rate when driving or operating machinery.

Patients should be informed that in very rare cases, drowsiness may occur, which could affect their ability to drive or operate complex machinery.

Method of Administration and Dosage

The medication is taken orally, independent of food intake.

Children:

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

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

For accurate dosing, it is recommended to use measuring devices with appropriate graduations.

The duration of treatment depends on the severity and course of the disease.

Treatment of intermittent allergic rhinitis (symptoms present less than 4 days per week or 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 longer than 4 weeks), treatment should continue throughout the entire period of allergen exposure.

Children. The efficacy and safety of Edem® syrup in children under 6 months of age have not been established. The medication 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.

Overdose.

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

During clinical trials in adults and adolescents, administration of desloratadine at doses up to 45 mg (9 times higher than the recommended dose) 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 approved indications, including allergic rhinitis and chronic idiopathic urticaria, adverse events were reported 5% more frequently in patients receiving a 5 mg daily dose compared to those 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 studies of Edem® syrup 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 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, aggression, and excitation.

In the postmarketing period, the following adverse reactions have been observed (frequency unknown): QT interval prolongation, arrhythmia, and bradycardia.

Other adverse reactions reported very rarely during the postmarketing period are listed in the table below.

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 has been observed compared to the placebo group. In clinical studies, Edem® at a single daily dose of 7.5 mg showed no effect on psychomotor performance.

Shelf life.

2 years.

Shelf life after opening the bottle – 90 days.

Do not use the medicinal product after the expiry date stated on the packaging.

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

Packaging. 60 ml or 100 ml in a brown glass bottle with a screw neck, closed with a screw cap with a tamper-evident ring or a tamper-evident screw cap. One bottle together with a measuring spoon/dosing spoon or dosing glass/measuring glass is packed in a cardboard box.

Classification. Over-the-counter (without prescription).

Manufacturer: JSC "Farmak".

Manufacturer's address and place of business:

74, Kyrylivska Street, Kyiv, 04080, Ukraine.