Blogir-3

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT BLOGIR-3

Composition:

Active ingredient: desloratadine;

1 tablet contains 5 mg of desloratadine;

Excipients: polacrilin potassium; citric acid, monohydrate; iron oxide red (E 172); magnesium stearate; tutti-frutti liquid flavoring; sodium croscarmellose; aspartame (E 951); microcrystalline cellulose; mannitol (E 421).

Pharmaceutical form. Orally disintegrating tablets.

Main physicochemical characteristics: round, flat, brown-pink tablets with specks, beveled edges, and embossing "5" on one side.

Pharmacotherapeutic group. Antihistamines for systemic use.

ATC code R06AX27.

Pharmacological Properties.

Pharmacodynamics.

Desloratadine is a non-sedating, long-acting antihistamine that exerts a selective antagonistic effect on peripheral H1-receptors. After oral administration, desloratadine selectively blocks peripheral histamine H1-receptors.

In in vitro studies, desloratadine demonstrated anti-allergic and anti-inflammatory properties on endothelial cells. This was manifested by inhibition of the release of pro-inflammatory cytokines such as IL-4, IL-6, IL-8, and IL-13 from human mast cells/basophils, as well as inhibition of adhesion molecule expression, including P-selectin. The clinical significance of these observations has yet to be confirmed.

In high-dose clinical studies where desloratadine was administered daily at doses up to 20 mg for 14 days, no statistically significant cardiovascular effects were observed. In a clinical pharmacology study using 45 mg per day (10 times the maximum recommended daily clinical dose) for 10 days, no QT interval prolongation was observed.

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. Desloratadine effectively controlled symptoms for 24 hours.

Desloratadine barely penetrates the central nervous system. In controlled clinical trials, at the recommended dose of 5 mg per day, the incidence of somnolence did not differ from the placebo group. In clinical studies, a single dose of desloratadine at 7.5 mg daily did not affect psychomotor performance.

Desloratadine effectively reduced the severity of seasonal allergic rhinitis, as measured by the total score of the rhinoconjunctivitis quality of life questionnaire. The greatest improvement was observed in questionnaire items related to practical problems and daily activities limited by symptoms.

Chronic idiopathic urticaria was studied in a clinical model of urticaria conditions. Since histamine release is a causative factor in all forms of urticaria, desloratadine is expected to effectively alleviate symptoms in other forms of urticaria, including chronic idiopathic urticaria.

Pharmacokinetics.

Absorption.

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

In a pharmacokinetic study where patient demographics were comparable to the general population with seasonal allergic rhinitis, approximately 4% of participants exhibited higher desloratadine concentrations. This proportion may vary depending on ethnicity. Maximum desloratadine concentration was approximately 3 times higher at about 7 hours, and the terminal elimination half-life was approximately 89 hours. The safety profile in these patients did not differ from that in the general population.

Distribution.

Desloratadine is moderately bound to plasma proteins (83–87%). No evidence of clinically significant accumulation was observed after administration of desloratadine doses (5 to 20 mg) once daily for 14 days.

Biotransformation.

The enzyme responsible for desloratadine metabolism has not yet been identified, thus some drug interactions cannot be completely ruled out. Desloratadine does not inhibit CYP3A4 in vivo. In vitro studies have demonstrated that the drug does not inhibit CYP2D6, nor is it a substrate or inhibitor of P-glycoprotein.

Elimination.

In a single-dose study of desloratadine 7.5 mg, food intake (a high-fat, high-calorie breakfast) did not affect the pharmacokinetics of desloratadine. It has also been established that grapefruit juice does not affect the pharmacokinetics of desloratadine.

Clinical characteristics.

Indications.

Relief of symptoms associated with:

• allergic rhinitis (see section "Pharmacological properties");
• urticaria (see section "Pharmacological properties").

Contraindications.

Hypersensitivity to desloratadine or to any of the excipients of the medicinal product, or to loratadine.

Interaction with other medicinal products and other forms of interaction.

In clinical studies of desloratadine tablets, no clinically significant interactions were observed when co-administered with erythromycin or ketoconazole.

In clinical pharmacological studies, no enhancement of the negative effect of ethanol on psychomotor function was observed when the drug was used concomitantly with alcohol. However, during the post-marketing period, cases of alcohol intolerance and alcohol intoxication during drug use have been reported. Therefore, caution should be exercised when consuming alcohol during treatment.

Special precautions for use

In patients with severe renal impairment, desloratadine should be administered under medical supervision. Patients with rare hereditary conditions of galactose intolerance, lactase deficiency, or glucose-galactose malabsorption should not take this medication. Desloratadine should not be taken by patients with phenylketonuria due to the presence of aspartame. The product contains less than 1 mmol of sodium per dose, i.e., it is practically sodium-free.

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 (see section "Adverse reactions"). The physician should consider discontinuing desloratadine treatment in patients who experience a seizure during therapy.

Use during pregnancy or breastfeeding

Desloratadine did not show teratogenic effects in animal studies. However, the safety of desloratadine during pregnancy has not been established; therefore, use of desloratadine during pregnancy is not recommended.

Breastfeeding

Desloratadine passes into breast milk; therefore, the use of this medication is not recommended in breastfeeding women.

Ability to influence reaction rate while driving or operating machinery

Clinical studies evaluating the ability to drive have shown no impairment in patients taking desloratadine. Nevertheless, patients should be informed that, very rarely, some individuals may experience somnolence, which could affect their ability to drive or operate complex machinery.

Administration and Dosage

For adults and adolescents (aged 12 years and older), take 1 tablet once daily, regardless of food intake, to relieve symptoms associated with allergic rhinitis (including intermittent and persistent allergic rhinitis) and urticaria. The tablet should not be taken with water or other liquids. The tablet should be taken immediately after opening the blister pack.

For treatment of intermittent allergic rhinitis (symptoms present for less than 4 days per week or less than 4 weeks), therapy should be administered based on patient history: discontinue after symptoms resolve and resume upon their recurrence.

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

There are limited clinical data on the efficacy of desloratadine tablets in adolescents aged 12 to 17 years (see section "Adverse Reactions").

The efficacy and safety of desloratadine in children under 12 years of age have not been established.

Overdose

In case of overdose, standard measures should be taken to remove the unabsorbed active substance. Symptomatic and supportive treatment is recommended. In clinical studies where desloratadine was administered at doses of 45 mg (9 times the recommended dose), no clinically significant adverse reactions were observed. Desloratadine is not removed by hemodialysis; its elimination via peritoneal dialysis has not been established.

Adverse Reactions

In clinical trials evaluating the use of the drug for its approved indications, including allergic rhinitis and chronic idiopathic urticaria, adverse reactions were reported 3% 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%).

Children. In clinical trials involving 578 adolescents aged 12 to 17 years, the most commonly reported adverse reaction was headache, observed in 5.9% of patients taking desloratadine and in 6.9% of those receiving placebo.

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

In the post-marketing period, the following events were observed (frequency unknown): QT interval prolongation, arrhythmias, and bradycardia.

Other adverse reactions reported very rarely during the post-marketing period, classified by system organ class and frequency of occurrence, are as follows: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); frequency not known (cannot be estimated due to limited available data).

Psychiatric Disorders

Very rare: hallucinations.

Frequency not known: abnormal behavior, aggression, depressed mood.

Nervous System Disorders

Common: headache.

Very rare: dizziness, somnolence, insomnia, psychomotor hyperactivity, convulsions.

Cardiac Disorders

Very rare: tachycardia, palpitations.

Frequency not known: QT interval prolongation, supraventricular tachyarrhythmia.

Gastrointestinal Disorders

Common: dry mouth.

Very rare: abdominal pain, nausea, vomiting, dyspepsia, diarrhea.

Hepatobiliary Disorders

Very rare: increased liver enzyme levels, increased bilirubin, hepatitis.

Frequency not known: jaundice.

Eye Disorders

Frequency not known: dry eyes.

Musculoskeletal and Connective Tissue Disorders

Very rare: myalgia.

Skin and Subcutaneous Tissue Disorders

Frequency not known: photosensitivity.

General Disorders and Administration Site Conditions

Common: increased fatigue.

Very rare: hypersensitivity reactions (such as anaphylaxis, Quincke's edema, dyspnea, pruritus, rash, and urticaria).

Frequency not known: asthenia.

Investigations

Frequency not known: weight gain.

Metabolism and Nutrition Disorders

Frequency not known: increased appetite.

An increased frequency of seizure episodes has been reported in patients aged 0 to 19 years following desloratadine use. Among children aged 0–4 years, the increase was 37.5 per 100,000 patient-years, while in patients aged 5–19 years, this rate was 11.3 per 100,000 patient-years (see section "Special Warnings and Precautions for Use").

Reporting of Suspected Adverse Reactions

Reporting suspected adverse reactions after drug authorization 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 a temperature not exceeding 25 °C.

Keep out of reach and sight of children.

Packaging.

10 tablets in a blister. 1 or 3 blisters in a cardboard carton.

Prescription Status.

Over-the-counter (without prescription).

Manufacturer.

Belupo, Pharmaceuticals and Cosmetics, d.d.

Manufacturer's Address and Place of Business.

Danica 5, 48000 Koprivnica, Croatia.