Desalergan

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DESALERGAN

Composition:

Active substance: desloratadine;

1 ml of solution contains desloratadine 0.5 mg;

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

Pharmaceutical form. Oral solution.

Main physicochemical properties: clear, colorless solution with a fruity odor.

Pharmacotherapeutic group. Systemic antihistamines.

ATC code R06A X27.

Pharmacological properties.

Pharmacodynamics.

Mechanism of action

Desloratadine is a non-sedating, long-acting antihistamine with selective antagonistic activity at peripheral H1 receptors. After oral administration, desloratadine selectively blocks peripheral H1 histamine receptors, as it does not penetrate into the central nervous system (CNS).

In vitro studies have demonstrated that desloratadine exerts anti-allergic and anti-inflammatory properties on endothelial cells. These effects were 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 inhibition of adhesion molecule expression, such as P-selectin. The clinical relevance of these observations has yet to be confirmed.

Clinical efficacy and safety.

Pediatric population.

The efficacy of the oral solution containing desloratadine has not been studied in dedicated pediatric trials. 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). Treatment was well tolerated, as documented by clinical laboratory assessments, vital signs, and ECG (including QT interval duration).

Plasma concentrations of desloratadine at the recommended dose 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 adult studies may be extrapolated to children.

Adults and adolescents.

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 daily (10 times the maximum recommended clinical daily dose) for 10 days, no QT interval prolongation was observed.

Desloratadine penetrates minimally into the CNS. In controlled clinical trials, at the recommended dose of 5 mg daily, the incidence of somnolence was not different from placebo. In clinical studies, a single dose of desloratadine at 7.5 mg daily did not affect psychomotor performance. A single daily dose of 5 mg desloratadine in adults did not alter 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 somnolence was observed. No significant differences in psychomotor test results were found between groups receiving desloratadine and those receiving placebo (regardless of alcohol consumption).

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

In adults and adolescents with allergic rhinitis, desloratadine is 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 has not been specifically studied 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, it can also be classified as intermittent or persistent allergic rhinitis. 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 effectively relieves symptoms of seasonal allergic rhinitis, as evidenced by overall scores in the Rhinitis Quality of Life Questionnaire. The most significant improvements were 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, as the pathophysiological mechanisms are similar regardless of etiology, and including chronically affected patients in prospective trials is more feasible. Since histamine release is the underlying 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. The effect was maintained throughout the entire 24-hour dosing interval in both trials. As with other antihistamine trials in chronic idiopathic urticaria, patients identified as non-responders to antihistamine therapy were excluded. Itching relief of more than 50% was observed in 55% of patients treated with desloratadine compared to 19% of those receiving placebo. Desloratadine treatment 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 reached approximately 3 hours post-dose; 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 slow metabolizer phenotype was comparable in adults (6%) and children aged 2 to 11 years (6%), with a higher percentage observed in Black individuals (18% in adults and 16% in children) compared to Caucasian individuals (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, a 3-fold higher maximum plasma concentration (Cmax) was observed at 7 hours, with a terminal T½ of approximately 89 hours.

Similar pharmacokinetic parameters were observed in a multiple-dose pharmacokinetic study of desloratadine 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 3–4 times higher at 3–6 hours, with a T½ of approximately 120 hours. AUC was comparable between adult and pediatric slow metabolizers when receiving age-appropriate doses. 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; therefore, some drug interactions cannot be completely excluded. 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 was also shown not to affect desloratadine pharmacokinetics.

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 redness and itching, tearing, itching of the palate, and cough.

For relief of symptoms associated with urticaria, such as itching and rash.

Contraindications.

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

Interaction with other medicinal products and other forms of interaction.

No clinically significant interactions were observed when desloratadine was co-administered with erythromycin, azithromycin, fluoxetine, cimetidine, or ketoconazole. Since the enzyme responsible for desloratadine metabolism has not been identified, interactions with other medicinal products cannot be completely excluded.

In clinical pharmacological studies, desloratadine administered together with alcohol did not enhance the negative effects of ethanol on psychomotor function.

However, during the post-marketing period, cases of alcohol intolerance and alcohol intoxication have been reported during the use of the drug. Therefore, caution is necessary when consuming alcohol during treatment with desloratadine.

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

Effect on laboratory test results

The use of the drug 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 should be prescribed with 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 in patients who experience a seizure while taking the drug.

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

The medicinal product contains sorbitol; therefore, it is not recommended for patients with rare hereditary fructose intolerance, glucose-galactose malabsorption syndrome, or sucrase-isomaltase deficiency.

If a sugar intolerance has been diagnosed, patients should consult their physician before taking this medicinal product.

Use during pregnancy or breastfeeding.

Pregnancy.

Extensive data from use in pregnant women (over 1000 completed pregnancies) do 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 breastfeeding women.

Fertility.

There are no data available on the effect of the drug on fertility in men or women.

Ability to affect reaction speed 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 medications, patients should be advised to avoid activities requiring mental alertness, such as driving vehicles or operating machinery, until they know how they respond to the drug.

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 of desloratadine) once daily.

Treatment of intermittent allergic rhinitis (symptoms present less than 4 days per week or less than 4 weeks) should be managed 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 longer 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 in origin, and there is no evidence supporting the use of desloratadine for the treatment of infectious rhinitis.

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

For treatment, use the following dosage regimen:

• Children aged 6 to 11 years: 5 mL of solution (2.5 mg of desloratadine) once daily;
• Children aged 1 to 5 years: 2.5 mL of solution (1.25 mg of 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, apply standard measures to remove any unabsorbed active substance and administer 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; its elimination via peritoneal dialysis has not been established.

Adverse Reactions

In clinical trials for the approved indications, including allergic rhinitis and chronic idiopathic urticaria, adverse events associated with 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%).

Pediatric Population

In clinical trials conducted in the pediatric population, desloratadine syrup was administered to 246 children aged 6 months to 11 years. The overall incidence of adverse events in children aged 2 to 11 years was similar in both the desloratadine and placebo groups. In infants and younger 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 trial 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, aggression, and agitation.

Desloratadine penetrates the CNS to a minimal extent. When administered at the recommended adult dose of 5 mg, no increase in the incidence of somnolence was observed compared to the placebo group.

Frequency is defined as very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare (<1/10000), and not known (cannot be estimated based on available data).

Reporting of suspected adverse reactions

Reporting adverse reactions after marketing authorization of a medicinal product is of great importance. It enables 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 through the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life. 3 years.

Shelf life after first opening of the bottle: 3 months.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of the reach and sight of children.

Packaging.

120 ml in a bottle, 1 bottle with a measuring cup in a cardboard box.

Availability.

Over-the-counter.

Manufacturer.

VETPROM AD, production unit Vpharma / VETPROM AD, the Vpharma site.

Manufacturer's address and place of business.

26 Otets Paisiy Str., Radomir 2400, Bulgaria.