Instructions for use Elysium oral solution 0.5 mg/ml plastic bottle 60 ml
Composition
active ingredient: desloratadine;
1 ml of solution contains 0.5 mg of desloratadine;
Excipients: disodium edetate; sodium citrate; citric acid, monohydrate; sorbitol (E 420); sucralose; propylene glycol; hypromellose; "Plum" flavoring; purified water.
Dosage form
Oral solution.
Main physicochemical properties: clear, colorless liquid with a characteristic odor.
Pharmacotherapeutic group
Antihistamines for systemic use. ATX code R06A X27.
Pharmacodynamics
Desloratadine is a long-acting, non-sedating antihistamine with selective peripheral H1-receptor antagonist activity. Desloratadine is the primary active metabolite of loratadine. After oral administration, desloratadine selectively blocks peripheral histamine H1-receptors, as it hardly penetrates the blood-brain barrier.
In vitro studies have demonstrated anti-allergic and anti-inflammatory properties of desloratadine. 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 the expression of the adhesion molecule P-selectin on endothelial cells. The clinical relevance of these observations is not yet fully established.
The efficacy of desloratadine oral solution in children has not been studied in specific studies. 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 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 studies of vital signs and ECG (including QT interval length).
When used 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, data on the effectiveness of desloratadine in adults can be extrapolated to children.
In high-dose clinical studies in which desloratadine was administered daily at a dose of up to 20 mg for 14 days, no statistically or clinically significant changes in the cardiovascular system were observed. In a clinical pharmacology study in which desloratadine was administered at a dose of 45 mg per day (9 times the clinical dose) for 10 days, no prolongation of the QT interval was observed.
Desloratadine does not cross the blood-brain barrier. At the recommended dose of 5 mg, the incidence of drowsiness did not exceed that in the placebo group. In clinical studies, desloratadine at a single dose of 7.5 mg had no effect on psychomotor activity.
In a study of a single daily dose of desloratadine 5 mg per day in adults, there were no changes in standard tests during the flight, including an increase in subjective feelings of sleepiness or other flight-related indicators. In clinical pharmacology trials of concomitant administration with alcohol, no increase in alcohol-related behavioral changes or increased sleepiness were found. There were no significant differences in the results of psychomotor tests in the groups taking desloratadine and those taking placebo (regardless of alcohol consumption).
In multiple-dose clinical studies of co-administration of desloratadine 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, itchy and runny nose, itchy and red eyes, watery eyes, and itchy palate. Desloratadine effectively controls symptoms for 24 hours. The efficacy of desloratadine tablets has not been conclusively demonstrated in clinical trials in patients 12 to 17 years of age.
In addition to the established classification of allergic rhinitis as seasonal or perennial, it can be classified as intermittent allergic rhinitis and persistent allergic rhinitis based on the duration of symptoms. Intermittent allergic rhinitis is defined as symptoms occurring less than 4 days per week or for at least 4 weeks. Persistent allergic rhinitis is defined as symptoms occurring 4 or more days per week and for more than 4 weeks.
Chronic idiopathic urticaria has been studied as a clinical model of urticarial conditions because, regardless of etiology, the pathophysiological mechanisms are similar and it is easier to enroll chronically ill patients in prospective studies. Since the causative factor for all urticarial diseases is histamine release, desloratadine is expected to be effective in relieving symptoms and other urticarial-related conditions other than 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 both trials, the effect was maintained throughout the 24-hour dosing interval. As in other trials of antihistamines, in chronic idiopathic urticaria, a smaller number of patients identified as non-responders to antihistamine treatment were excluded. Itch relief of more than 50% was observed in 55% of patients treated with desloratadine compared with 19% of patients treated with placebo. Treatment with desloratadine significantly reduced sleep-wake rhythm disturbances as measured by a four-point scale used to assess these variables.
Pharmacokinetics
Absorption. Plasma concentrations of desloratadine can be determined within 30 minutes of dosing. Desloratadine is well absorbed, with peak plasma concentrations occurring approximately 3 hours after dosing; the elimination half-life (T½) is approximately 27 hours. The extent of desloratadine accumulation was consistent with its T½ (approximately 27 hours) and once-daily dosing. The bioavailability of desloratadine was dose-proportional over the 5 to 20 mg range.
In pharmacokinetic and clinical studies, higher plasma concentrations of desloratadine were achieved in 6% of patients. The percentage of patients with the poor metabolizer phenotype was comparable in adults (6%) and children aged 2 to 11 years (6%), with a higher percentage in blacks (18% in adults and 16% in children) than in whites (2% in adults and 3% in children).
In a multiple-dose pharmacokinetic study of desloratadine tablets in healthy adult volunteers, four subjects were poor metabolizers of desloratadine. They had a 3-fold higher peak plasma concentration (Cmax) at 7 hours with a terminal phase T½ of approximately 89 hours.
Similar pharmacokinetic parameters were observed in a multiple-dose pharmacokinetic study conducted with the syrup in poor metabolizer children aged 2 to 11 years with allergic rhinitis. The area under the pharmacokinetic concentration-time curve (AUC) of desloratadine was approximately 6-fold higher and Cmax was 3-4-fold higher at 3-6 hours with a T½ of approximately 120 hours. AUC was similar in adults and poor metabolizer children when given an age-appropriate dose. The overall safety profile in these subjects did not differ from that in the general population. The effects of desloratadine in poor metabolizers in children under 2 years of age have not been studied.
In separate studies of single doses of desloratadine at the recommended dose in children, AUC and Cmax were found to be comparable to those in adults receiving a 5 mg dose of desloratadine (syrup).
Distribution: Desloratadine is moderately bound to plasma proteins (83-87%). When desloratadine doses (5 to 20 mg) are administered once daily for 14 days, there is no evidence of clinically significant accumulation of the active substance.
Metabolism. The enzyme responsible for the metabolism of desloratadine has not yet been identified, therefore some interactions with other drugs 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.
Conclusion: 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. Grapefruit juice was also found to have no effect on the pharmacokinetics of desloratadine.
Patients with renal impairment.
The pharmacokinetics of desloratadine were compared in patients with chronic renal failure (CKD) and healthy volunteers in one single-dose study and one multiple-dose study. In the single-dose study, plasma concentrations of desloratadine were approximately 2-fold higher in patients with mild and 2.5-fold higher in patients with moderate and severe CKD compared to healthy volunteers. In the multiple-dose study, steady-state concentrations were reached after day 11, and compared to healthy subjects, plasma concentrations of desloratadine were 1.5-fold higher in patients with mild and moderate CKD and 2.5-fold higher in patients with severe CKD. In both studies, changes in plasma concentrations (AUC and Cmax) of desloratadine and 3-hydroxydesloratadine were not clinically significant.
Indication
Elimination of symptoms associated with:
Contraindication
Hypersensitivity to the active substance or to any of the excipients of the drug or to loratadine.
Interaction with other medicinal products and other types of interactions
No clinically significant changes in the concentration of desloratadine in the blood plasma were observed with repeated use with ketoconazole, erythromycin, azithromycin, fluoxetine, cytamide. Due to the fact that the enzyme responsible for the metabolism of desloratadine has not been identified, interactions with other drugs cannot be completely excluded.
Food (fatty high-calorie breakfast) or grapefruit juice do not affect the distribution of desloratadine.
Impact 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 irritants.
Application features
In patients with severe renal insufficiency, Elysium should be administered under the supervision of a physician.
Desloratadine should be used with caution in patients with a history of seizures. Children may be more likely to develop a new seizure while receiving desloratadine. The physician should consider discontinuing desloratadine in patients who develop a seizure while receiving the drug.
Elysium contains sorbitol, so if the patient has been diagnosed with an intolerance to some sugars, you should consult your doctor before taking this medicine.
Ability to influence reaction speed when driving vehicles or other mechanisms
According to clinical studies, desloratadine has no or very little effect on the ability to drive and use machines. Patients should be informed that in very rare cases drowsiness may occur. Due to the individual response of the body to all drugs, it is recommended to advise patients not to perform activities requiring mental concentration, such as driving or operating machinery, until they have established their own reaction to the drug.
Use during pregnancy or breastfeeding
Pregnancy: A large amount of data on exposed pregnancies (more than 1000 pregnancy outcomes) indicate no malformative or foeto/neonatal toxicity of desloratadine. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. As a precautionary measure, desloratadine should not be used during pregnancy.
Breastfeeding. Desloratadine passes into breast milk, so its use in women who are breastfeeding is not recommended.
Fertility: There are no data on the effect of the drug on male and female fertility.
Method of administration and doses
To eliminate symptoms associated with allergic rhinitis (including intermittent and persistent) and urticaria, Elysium should be administered orally, regardless of meals, in the following doses:
Adults and children over 12 years of age: 10 ml of solution (5 mg desloratadine) once a day.
Children aged 6 to 11 years: 5 ml of solution (2.5 mg of desloratadine) once a day.
Children aged 1 to 5 years: 2.5 ml of solution (1.25 mg of desloratadine) once a day.
Treatment of intermittent allergic rhinitis (presence of symptoms less than 4 days a week or less than 4 weeks) should be carried out taking into account the anamnesis: stop after the disappearance of symptoms and resume after their reappearance. In persistent allergic rhinitis (presence of symptoms more than 4 days a week or more than 4 weeks), treatment should be continued throughout the entire period of contact with the allergen.
Children
Most cases of rhinitis in children under 2 years of age are infectious and there are no data to support the treatment of infectious rhinitis with desloratadine.
The efficacy and safety of Elysium oral solution for children under 1 year of age have not been established.
Overdose
In case of overdose, adverse reactions are similar to those observed at therapeutic doses, but the manifestations may be more severe.
In case of overdose, standard measures are used to remove unabsorbed active substance, and symptomatic treatment is used.
When desloratadine was used in doses up to 45 mg (9 times the recommended dose) in clinical studies in adults and adolescents, no clinically significant effects were observed.
Desloratadine is not removed by hemodialysis, and its removal by peritoneal dialysis has not been established.
Adverse reactions
In clinical trials for indications including allergic rhinitis and chronic idiopathic urticaria, adverse reactions to desloratadine were reported 3% more frequently in patients receiving the recommended dose of 5 mg daily than in patients receiving placebo.
The most frequently reported adverse reactions compared to placebo were fatigue (1.2%), dry mouth (0.8%), and headache (0.6%).
In clinical studies 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 the desloratadine and placebo groups. In infants and young children (6 to 23 months), the most common adverse reactions reported at a higher incidence than placebo were: diarrhea (3.7%), fever (2.3%), and insomnia (2.3%). In a subsequent study, no adverse events were observed in children aged 6 to 11 years after a single dose of desloratadine 2.5 mg oral solution.
In a clinical trial of 578 adolescent patients aged 12 to 17 years, the most common adverse reaction was headache, occurring in 5.9% of patients treated with desloratadine and 6.9% of patients treated with placebo.
There is a risk of psychomotor hyperactivity (abnormal behavior) associated with the use of desloratadine (which may manifest as anger and aggression, as well as agitation).
Desloratadine has little or no penetration into the central nervous system. At the recommended adult dose of 5 mg, there was no increase in the incidence of drowsiness compared to placebo.
Summary table of adverse reaction frequencies.
Frequencies are 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 from the available data).
| Organ classes/systems | Frequency of occurrence | Adverse reactions* |
| Mental disorders | very rarely | hallucinations |
| frequency unknown | abnormal behavior, aggression | |
| From the nervous system | often | headache |
| often (children under 2 years of age) | insomnia | |
| very rarely | dizziness, drowsiness, insomnia, psychomotor hyperactivity, convulsions | |
| From the heart | very rarely | tachycardia, rapid heartbeat |
| frequency unknown | QT prolongation, supraventricular tachyarrhythmia | |
| Gastrointestinal tract | often | dry mouth |
| often (children under 2 years of age) | diarrhea | |
| very rarely | abdominal pain, nausea, vomiting, dyspepsia, diarrhea | |
| Hepatobiliary system | very rarely | increased liver enzymes, increased bilirubin, hepatitis |
| frequency unknown | jaundice | |
| Musculoskeletal and connective tissue disorders | very rarely | myalgia |
| Skin and subcutaneous tissue disorders | frequency unknown | photosensitivity |
| Metabolic and nutritional disorders | frequency unknown | increased appetite |
| General violations | often | increased fatigue |
| often (children under 2 years of age) | fever | |
| very rarely | hypersensitivity reactions (such as anaphylaxis, angioedema, shortness of breath, itching, rash and urticaria) | |
| frequency unknown | asthenia | |
| Research | frequency unknown | weight gain |
Expiration date
3 years.
Once the container is opened, use within 6 months.
Storage conditions
Store at a temperature not exceeding 25 ° C. Keep out of the reach of children.
Packaging
60 ml or 120 ml in a polyethylene terephthalate container or 120 ml in a glass container closed with a tamper-evident lid with a dosing spoon and a dosing syringe in a pack.
Vacation category
Without a prescription.
Producer
Joint Ukrainian-Spanish enterprise "Sperco Ukraine".
Location of the manufacturer and address of its place of business
21027, Ukraine, Vinnytsia, 600-anniversary St., 25.
Phone: + 38(0432)52-30-36. E-mail: trade@sperco.com.ua
www.sperco.ua
