Allergozan®

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ALEGRGOSAN® (ALLERGOSAN®)

Composition:

Active substance: desloratadine;

1 tablet contains 5 mg of desloratadine;

Excipients: microcrystalline cellulose, calcium hydrogen phosphate dihydrate, maize starch, hypromellose, talc, sodium stearyl fumarate, colloidal anhydrous silicon dioxide;

Film coating: Opadray II 33F 205000 blue (hypromellose, lactose monohydrate, titanium dioxide (E 171), macrogol 3350, indigo carmine aluminium lake (E 132), quinoline yellow aluminium lake (E 104)).

Pharmaceutical form. Film-coated tablets.

Main physicochemical characteristics: light-blue, round, biconvex film-coated tablets, 6 mm ± 0.2 mm in diameter.

Pharmacotherapeutic group. Systemic antihistamines.

ATC code R06A X27.

Pharmacological Properties

Pharmacodynamics

Desloratadine is a non-sedating, long-acting antihistamine with selective antagonistic activity at 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 in endothelial cells. This was manifested by inhibition of pro-inflammatory cytokine release—such as IL-4, IL-6, IL-8, and IL-13—from human mast cells/basophils, as well as suppression 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 a daily dose of 45 mg (10 times the maximum recommended clinical daily dose) for 10 days, no QT interval prolongation was observed.

In patients with allergic rhinitis, Allergozan**®** effectively relieved symptoms such as sneezing, rhinorrhea, nasal and ocular itching, tearing, eye redness, and palate itching. Allergozan**®** provided effective symptom control over 24 hours.

Desloratadine barely penetrates the central nervous system. In controlled clinical trials, at the recommended daily dose of 5 mg, the incidence of somnolence was not different from placebo. In clinical studies, a single dose of Allergozan**®** at a daily dose of 7.5 mg had no effect on psychomotor performance.

Allergozan**®** effectively reduced the severity of seasonal allergic rhinitis, as measured by the total score of the Rhinitis 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. Since histamine release is a causative factor in all forms of urticaria, desloratadine is expected to effectively relieve symptoms in other forms of urticaria, including chronic idiopathic urticaria.

In two placebo-controlled, 6-week studies involving patients with chronic idiopathic urticaria, desloratadine effectively relieved itching and reduced the number and size of hives by the end of the first dosing interval. In each study, the effect lasted throughout the 24-hour dosing interval. Itching relief of more than 50% was observed in 55% of patients taking desloratadine, compared to 19% of patients receiving placebo. The drug had no significant impact on sleep or daytime activity.

Pharmacokinetics

Absorption. Desloratadine plasma concentrations 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 with demographic data comparable to the general population with seasonal allergic rhinitis, 4% of participants showed higher desloratadine concentrations. This proportion may vary depending on ethnicity. Maximum desloratadine concentration was approximately 3 times higher at around 7 hours, and the terminal elimination half-life was approximately 89 hours. The safety profile in these patients was not different from that in the general population.

Distribution. Desloratadine is moderately bound to plasma proteins (83–87%). With daily doses of desloratadine (5 to 20 mg) administered for 14 days, no evidence of clinically significant accumulation of the active substance was observed.

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

Elimination. In a single-dose study of 7.5 mg desloratadine, food intake (a high-fat, high-calorie breakfast) did not affect the pharmacokinetics of desloratadine. Grapefruit juice has also been shown not to affect desloratadine pharmacokinetics.

Clinical Characteristics.

Indications.

Desloratadine is indicated for adults and children aged 12 years and older for the relief of symptoms associated with:

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

Contraindications.

Hypersensitivity to the active substance 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.

According to 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 have been reported during treatment with the drug. Therefore, caution should be exercised when using alcohol concomitantly during desloratadine therapy.

Special precautions for use.

In patients with severe renal impairment, desloratadine should be administered under medical supervision.

Desloratadine should be used with caution in patients with a history of seizures, particularly in young children who may be more susceptible to developing new seizures during treatment with desloratadine. The physician may consider discontinuing desloratadine in patients who experience seizures while on treatment.

Desloratadine contains lactose. Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

Use during pregnancy or breastfeeding.

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

Breastfeeding. Desloratadine passes into breast milk; therefore, its use is not recommended in women who are breastfeeding.

Ability to affect reaction speed when driving or operating machinery.

In clinical studies assessing the ability to drive, no impairment was observed 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.

Method of Administration and Dosage

Administer orally, independent of food intake.

Adults and children aged 12 years and older: the recommended dose is 1 tablet once daily, regardless of food intake, for relief of symptoms associated with allergic rhinitis (including intermittent and persistent allergic rhinitis) and urticaria.

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 symptom resolution and resume upon symptom 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.

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

There are no established data on the efficacy and safety of desloratadine in children under 12 years of age.

Overdose.

In case of overdose, adverse reactions are similar to those observed at therapeutic doses, but symptoms may be more pronounced.

Symptoms. In clinical studies where desloratadine was administered at doses up to 45 mg (9 times the recommended dose), no clinically significant adverse reactions were observed.

Treatment. In case of overdose, standard measures to remove unabsorbed active substance should be applied. Symptomatic and supportive treatment is recommended. Desloratadine is not removed by hemodialysis; the possibility of its removal by peritoneal dialysis has not been established.

Adverse Reactions

In clinical studies of the approved indications, including allergic rhinitis and chronic idiopathic urticaria, adverse events related to desloratadine were reported 3% more frequently in patients receiving the recommended dose of 5 mg once daily 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 studies involving 578 adolescents aged 12 to 17 years, the most commonly reported adverse event was headache, occurring 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 agitation.

Other adverse reactions observed during the post-marketing period with unknown frequency include QT interval prolongation, arrhythmia, and bradycardia.

Summary table of adverse reaction frequencies.

Frequency is defined as 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 (cannot be estimated from available data).

Reporting of adverse reactions following marketing authorization of a medicinal product is of great importance. It enables continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, as well as their legal representatives, should 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. 3 years.

Storage conditions.

Keep out of reach of children.

Store at a temperature not exceeding 25 °C.

Packaging.

10 tablets in a blister. 1 or 3 blisters per cardboard box.

Availability category. Over-the-counter.

Manufacturer.

JSC "Sofarma".

Manufacturer's address and location of its business operations.

16 Iliensko Shose Str., Sofia, 1220, Bulgaria.