Desloratadine-teva

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Desloratadine-Teva

Composition:

Active substance: desloratadine;

1 ml of oral solution contains 0.5 mg of desloratadine;

Excipients: sorbitol solution, non-crystallizing (E 420); propylene glycol; citric acid monohydrate (E 330); sodium citrate (E 331); hypromellose 2910; sucralose; disodium edetate; flavouring*; purified water.

*Tutti frutti flavouring: flavouring substances and preparations, glycerol triacetate (E 1518), alpha-tocopherol (E 307).

Pharmaceutical form. Oral solution.

Main physicochemical characteristics: clear, colourless solution free from visible particles.

Pharmacotherapeutic group. Antihistamines for systemic use.

ATC code R06AX27.

Pharmacological Properties.

Pharmacodynamics.

Mechanism of action. Desloratadine is a non-sedating, long-acting histamine antagonist with selective antagonistic activity at peripheral H1 receptors. After oral administration, desloratadine selectively blocks peripheral H1-histamine receptors, as the substance penetrates poorly into the central nervous system.

In in vitro studies, desloratadine demonstrated antiallergic properties, including inhibition of proinflammatory 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, such as P-selectin on endothelial cells. The clinical significance of these observations remains to be confirmed.

Clinical efficacy and safety.

Children. The efficacy of desloratadine oral solution has not been studied in individual pediatric trials. However, the safety of use in children has been evaluated in three clinical studies of desloratadine syrup containing a similar concentration of the active substance as the oral solution.

Children aged 1–11 years requiring antihistamine therapy were administered desloratadine at a daily dose of 1.25 mg (ages 1 to 5 years) or 2.5 mg (ages 6 to 11 years). The treatment was well tolerated, as confirmed by clinical and laboratory test results, vital function monitoring, and ECG data, including QTc interval duration. Plasma concentrations of desloratadine were comparable between pediatric and adult populations when administered at recommended doses. Since the course of allergic rhinitis and chronic idiopathic urticaria, as well as the pharmacological profile of desloratadine, are similar in children and adults, efficacy data for desloratadine may be extrapolated to the pediatric population. The efficacy of desloratadine syrup has not been investigated in pediatric trials in children under 12 years of age.

Adults and adolescents. In a multiple-dose clinical study in adults and adolescents, in which 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, administration of desloratadine to adults and adolescents at a dose of 45 mg per day (9 times the clinical dose) for 10 days did not result in QTc interval prolongation.

Desloratadine penetrates minimally into the nervous system. In controlled clinical trials, the incidence of somnolence with the recommended daily dose of 5 mg in adults and adolescents did not differ from the placebo group. In clinical studies, a single 7.5 mg dose of desloratadine tablets did not affect psychomotor performance. In a single-dose study in adults, a 5 mg dose of desloratadine did not impair standard flight performance parameters, including subjective drowsiness or flight-related tasks.

In clinical pharmacological studies involving adults, concomitant use with alcohol did not increase alcohol-induced impairment of performance or drowsiness. No significant differences in psychomotor test results were observed between desloratadine and placebo groups, whether administered alone or with alcohol.

No clinically significant changes in plasma desloratadine concentrations were observed with repeated administration of ketoconazole and erythromycin.

In patients with allergic rhinitis, desloratadine effectively relieved and controlled symptoms such as sneezing, nasal itching and discharge, ocular itching and redness, lacrimation, and palate itching for up to 24 hours.

The efficacy of desloratadine tablets in adolescents aged 12–17 years has not been definitively demonstrated in clinical studies.

In addition to the conventional classification of allergic rhinitis into seasonal and perennial forms, allergic rhinitis may alternatively be classified by symptom duration as intermittent or persistent. Intermittent allergic rhinitis is defined as symptoms occurring less than 4 days per week or less than 4 weeks. Persistent allergic rhinitis is characterized by symptoms occurring 4 or more days per week or for more than 4 weeks.

Desloratadine tablets effectively alleviate the severity of seasonal allergic rhinitis, as evidenced 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 has been studied as a clinical model of urticarial disorders, as the pathogenic mechanisms are similar regardless of etiology. Histamine release is a causative factor in all urticarial disorders; therefore, desloratadine may effectively relieve symptoms of all urticarial disorders, including chronic idiopathic urticaria.

In two 6-week placebo-controlled studies involving patients with chronic idiopathic urticaria, desloratadine effectively reduced itching and decreased the number and size of wheals by the end of the first dosing interval. In each study, the effect lasted throughout the 24-hour dosing interval. As in other clinical trials of antihistamines in chronic idiopathic urticaria, a small number of patients considered non-responsive to antihistamines were excluded from the studies. A reduction in itching by more than 50% was observed in 55% of patients receiving desloratadine compared to 19% of patients receiving placebo. Desloratadine treatment also significantly reduced the impact of the disease on sleep and daytime activity, as measured by a four-point scale used to assess these changes.

Pharmacokinetics.

Absorption. Desloratadine plasma concentrations are detectable within 30 minutes after administration. Desloratadine is well absorbed, with peak concentrations reached approximately 3 hours after dosing. The elimination half-life is approximately 27 hours. The extent of desloratadine accumulation corresponds to its half-life (approximately 27 hours) and a once-daily dosing regimen.

In a series of clinical and pharmacokinetic studies, 6% of subjects exhibited higher desloratadine concentrations. The prevalence of the slow metabolizer phenotype was comparable in adults (6%) and children aged 2–11 years (6%), and higher among individuals of other ethnic groups (African descent: 18% of adults and 16% of children; Caucasian: 2% of adults and 3% of children, respectively).

In a multiple-dose pharmacokinetic study using desloratadine tablets in healthy adult volunteers, 4 subjects were identified as slow metabolizers. Their Cmax values, measured at approximately 7 hours, were on average 3 times higher, and the terminal elimination half-life was approximately 89 hours.

In a multiple-dose pharmacokinetic study using desloratadine syrup in slow metabolizer children aged 2–11 years with allergic rhinitis, desloratadine exposure (AUC) was approximately 6 times higher, and Cmax was approximately 3–4 times higher at 3–6 hours, with a terminal elimination half-life of approximately 120 hours. Exposure was similar in slow metabolizer adults and children when age-appropriate doses were administered. The safety profile in these patients 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 individual single-dose studies in pediatric patients receiving recommended doses, AUC and Cmax values of desloratadine were comparable to those in adults receiving 5 mg desloratadine syrup.

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

Bioequivalence between desloratadine tablets and syrup containing a similar concentration of the active substance has been demonstrated. Since the solution and syrup contain the same concentration of active ingredient, the solution is expected to be bioequivalent to both the syrup and the tablets.

Biotransformation. The enzyme responsible for desloratadine metabolism has not yet been identified; therefore, some interactions with other medicinal products cannot be fully 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 has also been shown not to affect desloratadine pharmacokinetics.

Patients with renal impairment. The pharmacokinetics of desloratadine in patients with chronic renal insufficiency was compared to that in healthy subjects in one single-dose and one multiple-dose study. In both studies, changes in exposure (AUC and Cmax) of desloratadine and 3-hydroxydesloratadine were not clinically significant.

Linearity/non-linearity. The bioavailability of desloratadine was proportional to the dose in the range of 5 mg to 20 mg.

Clinical characteristics.

Indications.

Desloratadine-Teva oral solution is indicated for use in adults, adolescents, and children from 1 year of age for the relief of symptoms associated with:

• allergic rhinitis (such as sneezing, itching and nasal discharge, eye itching and redness, lacrimation, palate itching);
• urticaria (such as itching and rash).

Contraindications.

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

Interaction with other medicinal products and other forms of interaction.

In clinical studies, no clinically significant interactions were observed when desloratadine tablets were administered concomitantly with erythromycin or ketoconazole. In clinical-pharmacological studies, no enhancement of the adverse effects of ethanol was observed when desloratadine tablets were administered together with alcohol. However, during the post-marketing period, cases of alcohol intolerance and alcohol intoxication have been reported during treatment with the medicinal product; therefore, caution should be exercised when consuming alcohol during desloratadine therapy.

Interaction studies have been conducted only in adults.

Special precautions for use.

The use of the medicinal product should be exercised with caution in patients with severe renal impairment.

Desloratadine should be used with caution in patients with a personal or family history of seizures. Children may be more susceptible to the development of new seizures during desloratadine treatment. The physician should decide whether to discontinue desloratadine treatment in patients who experience a seizure while taking the medicinal product.

Since it is difficult to differentiate allergic rhinitis from other forms of rhinitis in children under 2 years of age, medical history, physical examination findings, skin and laboratory tests should be considered, and the absence of upper respiratory tract infections and structural abnormalities should be confirmed.

Approximately 6% of adults and children aged 2–11 years have a slow metabolism of desloratadine, which is associated with increased drug exposure. The safety of desloratadine use in children aged 2–11 years does not differ between slow and normal metabolizers. The effects of desloratadine in children under 2 years of age who are slow metabolizers have not been studied.

The medicinal product contains sorbitol (1472 mg of sorbitol in 10 mL, equivalent to 21 mg/kg/day based on the daily dose for an adult weighing 70 kg). Therefore, it should not be administered to patients with hereditary fructose intolerance, glucose-galactose malabsorption, or sucrose-isomaltase deficiency. The additive effect of simultaneously administered products containing sorbitol (or fructose), as well as dietary intake of sorbitol (or fructose), should be taken into account. The sorbitol content in oral medicinal products may affect the bioavailability of other orally administered medicinal products taken concomitantly.

The medicinal product contains 38.46 mg of sodium in 10 mL, equivalent to 1.92% of the recommended maximum daily intake of 2 g sodium for adults. This should be considered for patients on a sodium-controlled diet.

This medicinal product contains 1023 mg of propylene glycol in 10 mL, equivalent to 14.16 mg/kg/day (calculated based on the daily dose for an adult weighing 70 kg).

Use during pregnancy or breastfeeding.

Pregnancy. Extensive data on desloratadine use during pregnancy (over 1000 cases) indicate no evidence of teratogenic or fetotoxic effects or adverse effects on the newborn. Animal studies have not revealed any direct or indirect adverse effects on reproductive function. As a precautionary measure, it is advisable to avoid using Desloratadine-Teva during pregnancy.

Breastfeeding. Desloratadine has been detected in the bodies of newborns/infants breastfed by women taking this medicinal product. The effect of desloratadine on newborns/infants is unknown. Breastfeeding women are advised to consider whether to discontinue breastfeeding or avoid using the medicinal product, taking into account the benefits of breastfeeding for the child and the therapeutic benefit of the medicinal product for the mother.

Fertility. Data on the effects on male or female fertility are lacking.

Ability to affect reaction speed when driving or operating machinery.

Clinical trial data indicate that desloratadine has no effect or only a negligible effect on reaction speed when driving or operating machinery. Patients should be informed that most people do not experience drowsiness. However, since individual responses to any medicinal product may vary, patients are advised not to engage in activities requiring mental alertness, such as driving a car or operating machinery, until they have determined their individual response to the medicinal product.

Method of administration and dosage.

Desloratadine-Teva solution is taken orally, independent of food intake.

Adults and adolescents (aged 12 years and older):

• 10 ml of solution (5 mg desloratadine) once daily.

Children. For treatment, the following dosing regimen should be used:

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

The safety and efficacy of Desloratadine-Teva oral solution in children under 1 year of age have not been established. There is limited clinical experience regarding the efficacy of desloratadine in children aged 1 to 11 years and adolescents aged 12 to 17 years.

It should be noted that most cases of rhinitis in children under two years of age are infectious, and there are no data confirming the effectiveness of desloratadine in treating infectious rhinitis.

Treatment of intermittent allergic rhinitis (symptoms present less than 4 days per week or less than 4 weeks) should be conducted based on patient history: discontinue after symptoms resolve and resume if symptoms reappear. For persistent allergic rhinitis (symptoms present more than 4 days per week or more than 4 weeks), treatment should be continued throughout the entire period of allergen exposure.

Children. The safety and efficacy of Desloratadine-Teva oral solution in children under 1 year of age have not been established.

Overdose.

According to post-marketing data, the adverse reaction profile associated with overdose was similar to that of therapeutic doses, but the manifestations were more pronounced.

Treatment. In case of overdose, standard measures aimed at removing the unabsorbed active substance should be applied, along with symptomatic and supportive therapy.

Desloratadine is not removed by hemodialysis; the possibility of its removal by peritoneal dialysis has not been established.

Symptoms. In clinical trials of multiple dosing of desloratadine up to 45 mg (9 times higher than the therapeutic dose), no clinically significant effects were observed.

Children. According to post-marketing experience, the adverse reaction profile associated with overdose is similar to that seen with therapeutic doses, although the manifestations may be more severe.

Adverse reactions.

Summary of safety profile.

Children. In clinical studies, desloratadine syrup was administered to a total of 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 younger children (6 to 23 months of age), the most common adverse events observed more frequently than with placebo were diarrhea (3.7%), fever (2.3%), and insomnia (2.3%). In an additional study of single 2.5 mg oral desloratadine solution administration in children aged 6–11 years, no adverse reactions were observed.

In a clinical study involving 578 adolescents aged 12 to 17 years, the most common adverse event was headache; this occurred in 5.9% of patients receiving desloratadine and in 6.9% of patients receiving placebo.

Adults and adolescents. At the recommended dose, in clinical studies involving adults and adolescents for indications including allergic rhinitis and chronic idiopathic urticaria, adverse events were reported 3% more frequently in patients than in the placebo group. The most frequently reported adverse effects compared to placebo were fatigue (1.2%), dry mouth (0.8%), and headache (0.6%).

Overall frequency of adverse reactions. The frequency of adverse reactions reported in clinical studies more frequently than placebo, and other adverse reactions reported in the post-marketing period, are listed below. The frequency of adverse reactions is classified as follows: 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).

Psychiatric disorders. Very rare: hallucinations. Frequency not known: abnormal behavior, aggression, depressed mood.

Metabolism and nutrition disorders. Frequency not known: increased appetite.

Eye disorders. Frequency not known: dry eyes.

Nervous system disorders. Common: headache, insomnia (in children under 2 years of age). Very rare: dizziness, somnolence, insomnia, psychomotor hyperactivity, seizures.

Cardiac disorders. Very rare: tachycardia, palpitations. Frequency not known: QT interval prolongation.

Gastrointestinal disorders. Common: dry mouth, diarrhea (in children under 2 years of age). Very rare: abdominal pain, nausea, vomiting, dyspepsia, diarrhea.

Hepatobiliary disorders. Very rare: increased liver enzyme levels, increased bilirubin levels, hepatitis. Frequency not known: jaundice.

Musculoskeletal and connective tissue disorders. Very rare: myalgia.

Skin and subcutaneous tissue disorders. Frequency not known: photosensitivity.

General disorders and administration site conditions. Common: fatigue, fever (in children under 2 years of age). Very rare: hypersensitivity reactions (such as anaphylaxis, angioedema, dyspnea, pruritus, rash, and urticaria). Frequency not known: asthenia.

Investigations. Frequency not known: weight gain.

Children. Other adverse reactions reported with unknown frequency in the post-marketing period include QT interval prolongation, arrhythmia, bradycardia, behavioral disturbances, and aggression.

A retrospective observational safety study identified an increased rate of seizures occurring in patients aged 0 to 19 years during desloratadine treatment compared to periods when they were not taking desloratadine.

Among children aged 0–4 years, the adjusted absolute increase was 37.5 (95% confidence interval (CI) 10.5–64.5) per 100,000 person-years, with a background rate of seizure onset of 80.3 per 100,000 person-years. Among patients aged 5–19 years, the adjusted absolute increase was 11.3 (95% CI 2.3–20.2) per 100,000 person-years, with a background rate of 36.4 per 100,000 person-years.

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after medicine authorization is important. It allows continued monitoring of the benefit-risk balance of the medicine. Healthcare professionals should report any suspected adverse reactions.

Shelf life. 3 years.

Shelf life after first opening of the bottle – 2 months.

Storage conditions. The medicinal product does not require special storage conditions. Store in the original packaging to protect from light. Keep out of the reach of children.

Packaging. 60 ml or 100 ml in a bottle, 1 bottle with a dosing syringe in a carton.

Category of supply. Over-the-counter.

Manufacturer. Balkanpharma-Troyan AD.

Manufacturer's address and location of operations.

1 Krayerchna Street, Troyan, 5600, Bulgaria.