Alerdez

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ALE RDEZ (ALERDEZ)

Composition:

Active substance: desloratadine;

1 ml of syrup contains 0.5 mg of desloratadine (calculated as 100% and dry substance);

Excipients: sodium benzoate (E 211); disodium edetate; sucrose; sorbitol (E 420); propylene glycol; sodium citrate; citric acid monohydrate; flavoring agent "Barberry"; colorant "Sunset Yellow FCF" (E 110); purified water.

Pharmaceutical form. Syrup.

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

Pharmacotherapeutic group. Antihistamines for systemic use.

ATC code: R06AX27.

Pharmacological Properties

Pharmacodynamics

Desloratadine is a selective blocker of peripheral histamine H1-receptors that does not cause 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 effect, desloratadine exerts anti-allergic and anti-inflammatory actions. It has been established that desloratadine inhibits a cascade of various reactions underlying the development of 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;
• 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 antihistaminic 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 desloratadine at doses up to 20 mg for 14 days was not associated with statistically significant clinical changes in the cardiovascular system. In a clinical pharmacological study, administration of desloratadine at 45 mg/day (9 times higher than the therapeutic dose) for 10 days did not result in 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, desloratadine 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 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 consecutive 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 relieved symptoms such as sneezing, nasal discharge and itching, as well as eye irritation, tearing, redness, and itching of the palate.

Pharmacokinetics

Desloratadine becomes detectable in blood plasma within 30 minutes after administration. Desloratadine effectively controls symptoms for 24 hours. Desloratadine is well absorbed. The maximum plasma concentration of desloratadine is reached on average within 3 hours, and 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). The bioavailability of desloratadine was dose-proportional in the range of 5 to 20 mg.

Desloratadine is moderately (83–87%) bound to plasma proteins. No signs of clinically significant accumulation were 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 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-over comparative studies with equivalent doses of desloratadine demonstrated bioequivalence between the tablet and syrup formulations.

Pharmacokinetic studies in pediatric populations have shown that AUC and Cmax values of desloratadine (when administered at recommended doses) are comparable to those 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, nasal discharge, itching, nasal swelling and congestion, as well as eye itching and redness, lacrimation, itching of the palate, and cough;
• urticaria, such as itching and 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, the possibility of interactions with other medicinal products cannot be completely excluded.

In clinical pharmacological studies, desloratadine did not enhance the negative effects of ethanol on psychomotor functions or drowsiness. However, during the post-marketing period, cases of alcohol intolerance and alcohol intoxication have been observed during desloratadine use. Therefore, caution should be exercised when consuming alcohol during treatment with this medicinal product.

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

Effect on diagnostic test results

Desloratadine 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

Desloratadine is not intended for the treatment of anaphylactic reactions. Patients who develop acute urticaria as part of an anaphylactic reaction together with respiratory and/or cardiovascular symptoms should seek immediate emergency medical assistance.

Desloratadine should be administered under medical supervision in patients with severe renal impairment.

Desloratadine should be used with caution in patients with a personal or family history of seizures. This is particularly relevant for young children, who may be more susceptible to developing a new seizure episode during desloratadine treatment. The physician should decide whether to discontinue desloratadine in patients who experience a seizure during treatment.

In children under 2 years of age, allergic rhinitis is particularly difficult to differentiate from other forms of rhinitis. The absence of upper respiratory tract infections or structural abnormalities should be carefully evaluated based on medical history, clinical symptoms, physical examination, appropriate laboratory tests, and allergological assessment.

The product contains sorbitol and therefore should not be used in patients with hereditary fructose intolerance, glucose-galactose malabsorption syndrome, or sucrase-isomaltase deficiency.

The product also contains the colouring agent Sunset Yellow FCF, which may cause allergic reactions.

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

Use during pregnancy or breastfeeding

Extensive data on the use of desloratadine during pregnancy (over 1000 cases) indicate no teratogenic or fetotoxic effects and no adverse effects on the newborn. Animal studies have not revealed any direct or indirect adverse effects on reproductive function. As a precautionary measure, it is advisable to avoid using the medicinal product Alerdez 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 infant and the therapeutic benefit of the drug for the mother.

Fertility
Data on effects on fertility are lacking.

Ability to affect reaction speed when driving or operating machinery

Clinical trial data indicate that desloratadine does not affect or has 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 mental alertness, such as driving a car or operating machinery, until they have determined their individual response to the medicinal product.

Method of Administration and Dosage

The medication should be taken orally, regardless of food intake.

Children:

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

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

To ensure accurate dosing, the dosing device provided in the package (a dosing pipette with measurement markings from 0.5 to 2.5 mL) should be used.

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

For intermittent allergic rhinitis (symptoms present for less than 4 days per week or less than 4 weeks), treatment should be based on patient history: discontinue upon symptom resolution and resume if symptoms reappear.

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 desloratadine 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, or 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 implemented, along with symptomatic treatment.

When desloratadine was administered at doses up to 45 mg (9 times the recommended dose) during clinical trials in adults and adolescents, no clinically significant effects were observed.

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

Adverse reactions.

Desloratadine hardly penetrates into the central nervous system. When used at the recommended adult dose of 5 mg, no increase in the frequency of somnolence has been observed compared to the placebo group. At a single dose of 7.5 mg, desloratadine had no effect on psychomotor performance.

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

Metabolism and nutrition disorders: increased appetite.

Psychiatric disorders: hallucinations, abnormal behaviour, aggression, depressive mood.

Nervous system: dizziness, somnolence, insomnia (frequently in children under 2 years of age), psychomotor hyperactivity, convulsions, headache.

Cardiovascular system: tachycardia, palpitations, QT interval prolongation, supraventricular tachyarrhythmia, bradycardia.

Gastrointestinal tract: dry mouth, diarrhoea (frequently in children under 2 years of age), abdominal pain, nausea, vomiting, dyspepsia.

Hepatobiliary system: increased activity of liver enzymes, increased plasma bilirubin levels, hepatitis, jaundice.

Musculoskeletal and connective tissue system: myalgia.

Immune system: hypersensitivity reactions (including anaphylaxis, Quincke's oedema, dyspnoea, pruritus, rash, urticaria).

Skin and subcutaneous tissue: photosensitivity reactions.

Eye disorders: dry eyes.

General disorders: increased fatigue, increased body temperature (frequently in children under 2 years of age), asthenia.

Investigations: weight gain.

Shelf life. 2 years.

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

Storage conditions. Store in the original packaging at a temperature not exceeding 25 °C. After opening the bottle, the shelf life of the medicinal product is 30 days at a temperature not exceeding 25 °C. Keep out of the reach of children.

Packaging. 50 ml in bottles, 100 ml in bottles or jars, supplied with a dosing device in a carton.

Supply category. Over-the-counter.

Manufacturer. Public joint-stock company "Scientific and Production Center "Borschagivsky Chemical and Pharmaceutical Plant".

Manufacturer's address and place of business.

17, Miru Street, Kyiv, 03134, Ukraine.