Desloratadine

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DESLORATADINE (DESLORATADINE)

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; sodium benzoate (E 211); disodium edetate; white crystalline sugar; raspberry flavor; carmoisine dye (E 122); purified water.

Pharmaceutical form. Syrup.

Main physicochemical properties: clear raspberry-colored liquid with a characteristic raspberry odor.

Pharmacotherapeutic group. Antihistamines for systemic use.

ATC code R06A X27.

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, desloratadine selectively blocks peripheral H1-histamine receptors, as the drug barely penetrates the blood-brain barrier.

Numerous studies have shown that in addition to its antihistaminic activity, desloratadine demonstrates anti-allergic and anti-inflammatory properties. It has been established that desloratadine suppresses the cascade of various reactions underlying allergic inflammation, namely:

• release of pro-inflammatory cytokines, including IL-4, IL-6, IL-8, and IL-13;
• release of pro-inflammatory 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 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 status, and ECG data (including QT interval duration).

During clinical trials, daily administration of the drug 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 desloratadine 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 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, allergic rhinitis can alternatively be classified by symptom duration into intermittent and persistent forms. Intermittent allergic rhinitis is defined as 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 the drug 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 relieved symptoms such as sneezing, rhinorrhea, nasal itching, as well as ocular irritation, tearing, redness, and palatal itching.

Pharmacokinetics.

Desloratadine becomes detectable in plasma within 30 minutes after administration. Desloratadine effectively controls symptoms for 24 hours. Desloratadine is well absorbed. The maximum plasma concentration (Cmax) 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 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 patients, in whom a significant increase in plasma drug levels and prolonged elimination half-life were noted. The prevalence of reduced metabolism may be influenced by race. However, this is currently considered clinically irrelevant.

Cross-comparative bioequivalence studies using the same drug dose demonstrated bioequivalence between the tablet and syrup formulations.

Pharmacokinetic studies in pediatric practice have shown that area under the plasma concentration–time curve (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 itching and redness of the 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, loratadine, or to any component of the medicinal product.

Interaction with other medicinal products and other forms of interaction.

No clinically significant changes in plasma concentration 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

The use of the medicinal product should be discontinued approximately 48 hours before performing skin tests, as antihistamines may prevent or reduce the occurrence 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 did not significantly differ between patients receiving desloratadine and those receiving placebo, either alone or in combination with alcohol.

In patients with severe renal impairment, the drug should be administered under medical supervision. 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 developing new seizures during treatment with desloratadine. Physicians should consider discontinuing desloratadine therapy in patients who experience a seizure while taking the drug.

Use during pregnancy or breastfeeding

Extensive data from use of desloratadine during pregnancy (over 1000 cases) indicate no evidence of teratogenic or fetotoxic effects or adverse effects on the newborn. Animal studies have not shown any direct or indirect adverse effects on reproductive function. As a precautionary measure, it is advisable to avoid using the drug during pregnancy.

Desloratadine is excreted in breast milk. Therefore, breastfeeding women should decide whether to discontinue breastfeeding or to avoid using the drug, taking into account the benefits of breastfeeding for the infant and the therapeutic benefits of the drug for the mother.

Fertility
Data on the effect of desloratadine on fertility are lacking.

Ability to affect reaction speed when driving vehicles or operating machinery

Clinical study data indicate that desloratadine has no effect or only a negligible effect on the ability to drive vehicles or operate machinery. Patients should be informed that most people do not experience drowsiness. Individual responses to medications may vary. Patients should avoid activities requiring mental alertness, such as driving a car or operating machinery, until they have determined their individual response to the drug.

Dosage and Administration

To relieve symptoms associated with allergic rhinitis (including both intermittent and persistent forms) and urticaria, desloratadine should be taken regardless of food intake at the doses specified below.

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

For accurate dosing, it is recommended to use a measuring spoon with graduations.

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

Treatment of intermittent allergic rhinitis (symptoms present for fewer than 4 days per week or fewer than 4 weeks) should be guided by patient history: treatment should be discontinued upon symptom resolution and resumed if symptoms reappear. For persistent allergic rhinitis (symptoms present for more than 4 days per week or more than 4 weeks), treatment should be continued throughout the entire period of allergen exposure.

Children.

The efficacy and safety of the 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. For treatment, the following dosing regimen should be used:

• 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 implemented, along with symptomatic treatment.

When desloratadine has been administered at doses up to 45 mg (9 times the recommended dose), no clinically significant adverse reactions have been observed; however, an increase in the frequency or intensity of adverse reactions may occur.

Desloratadine is not effectively removed by hemodialysis. 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 3% more frequently in patients receiving a daily dose of 5 mg 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%). In clinical trials of the drug 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 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, very rarely reported 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, <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 incidence of somnolence was observed compared to the placebo group. In clinical studies, the drug administered at a single daily dose of 7.5 mg did not affect psychomotor performance.

Reporting of adverse reactions. Reporting of adverse reactions following the registration of the medicinal product is of great importance. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmacy professionals, as well as patients or their legal representatives, are encouraged to 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 in the original packaging at a temperature not exceeding 30 °C.

Keep out of the reach of children.

Packaging.

60 ml or 120 ml in a bottle. One bottle with a measuring spoon in a cardboard box.

Availability.

Over-the-counter.

Manufacturer.

JSC "Tekhnolohiya".

Manufacturer's address and location of its business activities.

8, Stara Prorina Street, Uman, Cherkasy region, 20300, Ukraine.