Blogger-3

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT BLOGIR-3

Composition:

Active substance: desloratadine;

1 ml of oral solution contains 0.5 mg of desloratadine;

Excipients: sorbitol solution, non-crystallizing (E 420); propylene glycol; hypromellose; sucralose; sodium citrate; tutti-frutti liquid flavoring; anhydrous citric acid; purified water.

Pharmaceutical form. Oral solution.

Main physicochemical properties: clear, colorless solution.

Pharmacotherapeutic group. Systemic antihistamines.

ATC code R06A X27.

Pharmacological Properties

Pharmacodynamics

Desloratadine is a selective blocker of peripheral histamine H1-receptors, which does not exhibit sedative effects.

After oral administration, desloratadine selectively blocks peripheral H1-histamine receptors and does not cross the blood-brain barrier.

Numerous studies have shown that in addition to its antihistaminic activity, desloratadine exerts anti-allergic and anti-inflammatory effects. It has been established that desloratadine suppresses the 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.

The safety of desloratadine use in children has been demonstrated in three clinical studies. The drug was administered to children aged 1 to 11 years who required antihistamine therapy, at a daily dose of 1.25 mg (for ages 1 to 5 years) or 2.5 mg (for ages 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 studies, 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 pharmacological study, administration of desloratadine at a dose of 45 mg per day (9 times higher than the therapeutic dose) for 10 days did not cause QT interval prolongation.

Desloratadine does not cross the blood-brain barrier. When the recommended dose of 5 mg was used, the incidence of somnolence did not exceed that in the placebo group. During clinical studies, the drug did not affect psychomotor function when administered at doses up to 7.5 mg.

Pharmacokinetics

Absorption

Desloratadine plasma concentrations can be detected within 30 minutes after administration in adults and adolescents. Desloratadine is well absorbed, with peak plasma concentration (Cmax) reached on average within 3 hours. The elimination half-life is approximately 27 hours on average. The extent of desloratadine accumulation corresponds to its half-life (about 27 hours) and once-daily dosing. Desloratadine bioavailability was dose-proportional in the range of 5 mg to 20 mg.

In a series of pharmacokinetic and clinical studies, 6% of subjects achieved higher desloratadine concentrations. The prevalence of this poor metabolizer phenotype was comparable among adults (6%) and pediatric subjects aged 2 to 11 years (6%), and was higher among Black individuals (18% of adults, 16% of pediatric subjects) than among Caucasians (2% of adults, 3% of pediatric subjects) in both populations.

Distribution

Desloratadine is moderately bound (83%–87%) to plasma proteins. There is no evidence of clinically significant accumulation of the active substance after single daily doses of desloratadine (5 mg to 20 mg) administered to adults and adolescents over 14 days.

Biotransformation

The enzyme responsible for desloratadine metabolism has not yet been identified; therefore, certain interactions with other medicinal products cannot be completely ruled out. Desloratadine does not inhibit CYP3A4 in vivo, and in vitro studies have shown that the drug does not inhibit CYP2D6 and is neither a substrate nor an inhibitor of P-glycoprotein.

Elimination

In a single-dose study of desloratadine 7.5 mg, food (a high-calorie, high-fat breakfast) did not affect the absorption of desloratadine. In another study, grapefruit juice did not influence desloratadine absorption.

Clinical characteristics.

Indications.

Relief of symptoms associated with:

• allergic rhinitis, such as sneezing, nasal discharge, itching, swelling and nasal congestion, eye itching and redness, tearing, itching of the palate and cough;
• urticaria, such as itching and rash.

Contraindications.

Hypersensitivity to desloratadine or 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 desloratadine plasma concentrations were observed when co-administered 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.

During clinical pharmacological studies, desloratadine did not enhance alcohol effects such as psychomotor impairment and drowsiness. However, during post-marketing use, cases of alcohol intolerance and intoxication have been reported. Therefore, caution is recommended when taking alcohol concomitantly.

Effect on laboratory test results

Treatment with Blogir-3 solution should be discontinued approximately 48 hours before skin testing, as antihistamines may prevent or reduce the manifestations of positive dermatological reactions to allergens.

Special precautions for use.

Patients with renal insufficiency should take this medication under medical supervision.

The product contains sorbitol and therefore should not be used in patients with hereditary fructose intolerance. Blogir-3 solution contains propylene glycol, which may cause symptoms similar to those observed after alcohol consumption. This medication contains less than 1 mmol of sodium (23 mg) per dose and is therefore considered practically sodium-free.

Desloratadine should be administered with caution to patients with a personal or family history of seizures, particularly in young children who are more susceptible to developing seizures during desloratadine treatment.

Physicians should consider discontinuing desloratadine in patients who experience a seizure during treatment.

Use during pregnancy or breastfeeding.

Available data from 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 this medicinal product during pregnancy.

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

Fertility.

There are no data available on the effect on fertility.

Ability to affect reaction speed when driving or operating machinery.

Clinical trial 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 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 know how they respond to the medication.

Dosage and Administration

Administer orally to adults and adolescents aged 12 years and older, regardless of food intake, 10 ml of oral solution (5 mg of desloratadine) once daily.

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

Children.

Administer orally to children aged 1 year and older, regardless of food intake, at the following doses:

• Children aged 1 to 5 years: 2.5 ml of oral solution (1.25 mg of desloratadine) once daily;
• Children aged 6 to 11 years: 5 ml of oral solution (2.5 mg of desloratadine) once daily;
• Adolescents aged 12 years and older: 10 ml of oral solution (5 mg of desloratadine) once daily.

Overdose.

In case of overdose, standard measures aimed at removing the unabsorbed active substance should be taken. If necessary, symptomatic and supportive treatment should be administered.

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

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

Adverse reactions

During clinical studies, the most commonly reported adverse reactions were fatigue (1.2%), dry mouth (0.8%), and headache (0.6%). In clinical studies of desloratadine in children aged 2 to 11 years, the incidence of adverse reactions was similar in both the oral solution group and the placebo group. In children aged 6 to 23 months, the most commonly reported adverse reactions were diarrhea (3.7%), fever (2.3%), and insomnia (2.3%).

Other adverse reactions reported very rarely during the post-marketing period are listed in the table below.

Adverse reactions occurring with the use of the medicinal product are classified by system organ classes and frequency of occurrence: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1000 to <1/100); rare (≥1/10,000 to <1/1000); very rare (<1/10,000); frequency not known (cannot be estimated due to limited available data).

Seizure frequency has been reported to increase in patients aged 0 to 19 years after administration of desloratadine. Among children aged 0–4 years, the increase was 37.5 per 100,000 patient-years, whereas in patients aged 5–19 years, this figure was 11.3 per 100,000 patient-years (see section "Special precautions for use").

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after marketing authorization of a medicinal product is an important procedure. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are required to report any suspected adverse reactions through the national reporting system.

Shelf life.

3 years.

Storage conditions.

Store at temperatures not exceeding 25 °C.

Keep out of the reach and sight of children.

Packaging.

60 ml or 120 ml of the preparation in a bottle. One bottle with a 2.5 ml or 5 ml measuring spoon supplied in a cardboard box.

Supply category.

Over-the-counter.

Manufacturer.

Belupo, lijekovi i kozmetika, d.d.

Manufacturer's address and place of business.

Danicica 5, 48000 Koprivnica, Croatia.