Allergozan®

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

Composition:

Active substance: desloratadine;

1 ml of oral solution contains 0.5 mg of desloratadine;

Excipients: propylene glycol; sodium citrate; citric acid monohydrate; disodium edetate; sorbitol solution, non-crystallizing (E 420); sucralose; hypromellose; cherry flavoring; purified water.

Pharmaceutical form. Oral solution.

Main physicochemical characteristics: clear, colorless syrup-like liquid.

Pharmacotherapeutic group.

Other antihistamines for systemic use. ATC code R06AX27.

Pharmacological Properties.

Pharmacodynamics.

Desloratadine is a potent, selective blocker of peripheral histamine H1-receptors, which does not produce sedative effects. Desloratadine is the primary active metabolite of loratadine.

After oral administration, desloratadine selectively blocks peripheral histamine H1-receptors, as it barely penetrates the blood-brain barrier.

In in vitro studies, desloratadine demonstrated anti-allergic and anti-inflammatory properties. These include 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 expression of adhesion molecules of P-selectin on endothelial cells. The clinical significance of these observations has not been fully established.

The efficacy of the oral solution containing desloratadine has not been studied in dedicated clinical trials in children. However, the safety of the syrup containing desloratadine at the same concentration has been demonstrated in three studies in children. Children aged 1 to 11 years with indications for antihistamine therapy received a daily dose of desloratadine of 1.25 mg (children aged 1 to 5 years) or 2.5 mg (children aged 6 to 11 years). The treatment was well tolerated, as documented by clinical laboratory tests, vital signs, and ECG (including QT interval duration).

When administered at the recommended dose, plasma concentrations of desloratadine were comparable in children and adults. Since the course of allergic rhinitis and chronic idiopathic urticaria, as well as the safety profile of desloratadine, are similar in children and adults, efficacy data from studies in adults may be extrapolated to children.

In clinical studies of high doses, where desloratadine was administered daily at doses up to 20 mg for 14 days, no statistically or clinically significant cardiovascular effects were observed. In a clinical pharmacology study where desloratadine was administered at a dose of 45 mg per day (9 times the clinical dose) for 10 days, no QT interval prolongation was observed.

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 studies, a single 7.5 mg dose of desloratadine had no effect on psychomotor performance.

In a study of a single daily dose of 5 mg desloratadine in adults, no changes were observed in standard flight performance tests, including no increase in subjective drowsiness or other flight-related parameters. In clinical pharmacology trials evaluating co-administration with alcohol, no increase in alcohol-related behavioral changes or enhanced drowsiness was observed. No significant differences were found in psychomotor test results between groups receiving desloratadine and those receiving placebo (regardless of alcohol consumption).

In clinical studies with multiple dosing of desloratadine co-administered with ketoconazole and erythromycin, no clinically significant changes in plasma concentrations of desloratadine were observed.

In adults and adolescents with allergic rhinitis, desloratadine tablets are effective in relieving symptoms such as sneezing, nasal itching and discharge, eye itching and redness, tearing, and palate itching. Desloratadine effectively controls symptoms for 24 hours. The efficacy of desloratadine tablets has not been definitively established in clinical trials involving patients aged 12 to 17 years.

In addition to the established classification of allergic rhinitis into seasonal and perennial forms based on symptom duration, allergic rhinitis can also be classified as intermittent or persistent, depending on symptom frequency. Intermittent allergic rhinitis is defined as symptoms occurring less than 4 days per week or for less than 4 consecutive weeks. Persistent allergic rhinitis is defined as symptoms occurring on 4 or more days per week and for more than 4 consecutive weeks.

Desloratadine tablets effectively relieve symptoms of seasonal allergic rhinitis, as evidenced by overall scores in the Rhinoconjunctivitis Quality of Life Questionnaire. The most significant improvements are observed in the domains of practical problems and daily activities limited by symptoms.

Chronic idiopathic urticaria has been studied as a clinical model of urticarial conditions because, regardless of etiology, the pathophysiological mechanisms are similar, and including chronically affected patients in prospective studies is more feasible. Since histamine release is the causative mechanism in all urticarial conditions, desloratadine is expected to be effective in relieving symptoms and other urticaria-related conditions beyond chronic idiopathic urticaria, as recommended in clinical guidelines.

In two placebo-controlled, 6-week trials in patients with chronic idiopathic urticaria, desloratadine was effective in relieving itching and reducing the size and number of wheals as early as the end of the first dosing interval. In each trial, the effect was maintained throughout the entire 24-hour dosing interval. As in other antihistamine trials, patients identified as non-responders to antihistamine therapy were excluded from the studies. Itching relief of more than 50% was observed in 55% of patients treated with desloratadine compared to 19% of patients receiving placebo. Treatment with desloratadine significantly reduced sleep disturbance and insomnia, measured using a four-point scale used to assess these variables.

Pharmacokinetics.

Absorption. Desloratadine plasma concentrations can be detected within 30 minutes after administration. Desloratadine is well absorbed, with peak plasma concentration (Cmax) reached approximately 3 hours after dosing; the elimination half-life (T½) is approximately 27 hours. The extent of desloratadine accumulation corresponds to its T½ (approximately 27 hours) and the once-daily dosing regimen. Desloratadine bioavailability was dose-proportional in the range of 5 to 20 mg.

In pharmacokinetic and clinical studies, higher plasma concentrations of desloratadine were observed in 6% of patients. The percentage of patients with a slow metabolizer phenotype was comparable in adults (6%) and children aged 2 to 11 years (6%), with a higher percentage observed in individuals of African descent (18% in adults and 16% in children) compared to those of Caucasian descent (2% in adults and 3% in children).

In a multiple-dose pharmacokinetic study of desloratadine tablets in healthy adult volunteers, four participants were identified as slow metabolizers. In these individuals, Cmax was approximately 3 times higher at 7 hours, and the terminal T½ was approximately 89 hours.

Similar pharmacokinetic parameters were observed in a multiple-dose pharmacokinetic study with syrup in slow metabolizer children aged 2 to 11 years with allergic rhinitis. The area under the plasma concentration-time curve (AUC) of desloratadine was approximately 6 times higher, and Cmax was 3 to 4 times higher at 3 to 6 hours, with a T½ of approximately 120 hours. AUC was similar in adult and pediatric slow metabolizers when age-appropriate doses were administered. The overall safety profile in these individuals did not differ from that in the general population. The effects of desloratadine in slow metabolizers under 2 years of age have not been studied.

In separate single-dose studies of desloratadine at the recommended dose in children, AUC and Cmax values were comparable to those in adults receiving a 5 mg dose of desloratadine (syrup).

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

Metabolism. The enzyme responsible for desloratadine metabolism has not yet been identified, so 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 and is neither a substrate nor an 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 the pharmacokinetics of desloratadine.

Clinical characteristics.

Indications.

For relief of symptoms associated with:

• allergic rhinitis (sneezing, nasal discharge, itching, nasal swelling and congestion, eye itching and redness, lacrimation, itching of the palate, and cough);
• urticaria (itching, rash).

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.

No clinically significant changes in plasma concentrations of desloratadine were observed after repeated 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 excluded.

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 skin testing, as antihistamines may prevent or reduce the appearance of positive dermatological reactions to allergens.

Special precautions for use

Desloratadine should be used with particular caution under medical supervision in patients with severe renal impairment.

If intolerance to certain sugars is known, consult a physician before taking this medicinal product.

Desloratadine should be prescribed with particular caution to patients with a history of seizures. Children may be more susceptible to developing new seizures during desloratadine treatment. The physician should consider discontinuing desloratadine therapy in patients who experience a seizure during treatment.

Use during pregnancy or breastfeeding

Pregnancy. A large amount of data on the use of desloratadine in pregnant women (over 1000 completed pregnancies) does not indicate any teratogenic or fetal/neonatal toxicity of desloratadine. Animal studies have not revealed any direct or indirect adverse effects related to reproductive toxicity. As a precautionary measure, desloratadine should not be used during pregnancy.

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

Fertility. There are no data available on the effect of the medicinal product on fertility in men or women.

Ability to influence the speed of reactions when driving or operating machinery

According to clinical studies, desloratadine has no effect or only a negligible effect on the ability to drive vehicles or operate machinery. Patients should be informed that somnolence may occur very rarely. Due to individual responses to medicinal products, patients should be advised not to engage in activities requiring mental alertness, such as driving vehicles or operating machinery, until they know how they respond to the medicinal product.

Method of administration and dosage.

Administer orally, regardless of food intake.

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

Intermittent allergic rhinitis (symptoms present less than 4 days per week or for less than 4 weeks) should be treated according to patient history: discontinue upon symptom resolution and resume upon symptom recurrence.

For persistent allergic rhinitis (symptoms present more than 4 days per week or for more than 4 weeks), treatment should continue throughout the entire period of allergen exposure.

Children.

Most cases of rhinitis in children under 2 years of age are infectious, and there is no evidence supporting the use of desloratadine for treating infectious rhinitis.

The efficacy and safety of the syrup in children under 1 year of age have not been established.

The following dosing regimen should be used for treatment:

• Children aged 6 to 11 years: 5 ml of solution (2.5 mg desloratadine) once daily;
• Children aged 1 to 5 years: 2.5 ml of solution (1.25 mg desloratadine) once daily.

Overdose.

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

In the event of overdose, standard measures to remove unabsorbed active substance should be applied, along with symptomatic treatment.

When desloratadine was administered at doses up to 45 mg (9 times higher than the recommended dose) in clinical studies 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

In clinical studies for the approved indications, including allergic rhinitis and chronic idiopathic urticaria, adverse events associated with desloratadine in patients receiving the recommended dose of 5 mg once daily were reported 3% more frequently than in patients receiving placebo.

The most commonly reported adverse reactions compared to placebo were: fatigue (1.2%), dry mouth (0.8%), and headache (0.6%).

Pediatric Population

In clinical studies conducted in the pediatric population, desloratadine syrup was administered to 246 children aged 6 months to 11 years. The overall incidence of adverse reactions in children aged 2 to 11 years was similar in both the desloratadine and placebo groups. In infants and young children (6 to 23 months of age), the most commonly reported adverse reactions occurring at a higher frequency compared to placebo were: diarrhea (3.7%), fever (2.3%), and insomnia (2.3%). In another study following a single 2.5 mg oral dose of desloratadine solution in children aged 6 to 11 years, no adverse reactions were observed.

In a clinical study involving 578 adolescent patients aged 12 to 17 years, the most commonly reported adverse reaction was headache, occurring in 5.9% of patients receiving 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.

Desloratadine scarcely penetrates the central nervous system. When administered at the recommended adult dose of 5 mg, no increase in the incidence of somnolence was observed compared to the placebo group.

Summary table of adverse reaction frequencies.

Frequency is defined as: very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1,000, < 1/100), rare (≥ 1/10,000, < 1/1,000), very rare (< 1/10,000), and not known (cannot be estimated from the available data).

Reporting of suspected adverse reactions

Reporting of adverse reactions after marketing authorization of the medicinal product is of major importance. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy of the medicinal product via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Shelf life after opening the bottle – 3 months.

Storage conditions.

Keep out of the reach of children.

Keep in the original packaging to protect from light.

This medicinal product does not require special storage temperature conditions.

Packaging.

120 ml of solution in a glass or PET bottle.

1 bottle with a measuring cup and dosing syringe in a cardboard pack.

Availability. Over-the-counter.

Manufacturer.

Sofarma AD.

Manufacturer's address and location of the site of manufacturing activity.

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