Desloratadine-teva

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Desloratadine-Teva (Desloratadine-Teva)

Composition:

Active ingredient: desloratadine;

One film-coated tablet contains 5 mg of desloratadine;

Excipients: microcrystalline cellulose, pregelatinized starch (corn), mannitol (E 421), talc, magnesium stearate, hypromellose 6 mPa.s (E 464)*, titanium dioxide (E 171)*, macrogol 6000 (E 1521)*, indigo carmine aluminium lake (E 132)*.

*In the composition of the film coating Opadry Blue 03F20404.

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: blue, round, biconvex film-coated tablets, 6 mm in diameter, with "LT" embossed on one side.

Pharmacotherapeutic group. Antihistamines for systemic use.

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 poorly penetrates into the central nervous system.

In in vitro studies, desloratadine demonstrated antiallergic and anti-inflammatory 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 requires further confirmation.

Clinical efficacy and safety. In a multiple-dose clinical study, desloratadine was administered daily at doses up to 20 mg for 14 days, and no statistically or clinically significant cardiovascular changes were observed. In a clinical pharmacology study, administration of desloratadine at a dose of 45 mg per day (9 times higher than the recommended daily clinical dose) for 10 days did not result in QT interval prolongation.

Desloratadine penetrates the nervous system to a minimal extent. In controlled clinical trials, the incidence of somnolence with the recommended daily dose of 5 mg was not different from placebo. In clinical studies, a single dose of desloratadine at 7.5 mg per day did not affect psychomotor performance.

In patients with allergic rhinitis, desloratadine effectively relieved and controlled symptoms such as sneezing, rhinorrhea, nasal and ocular pruritus, tearing, conjunctival redness, and palatal 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.

Desloratadine effectively reduces the severity of seasonal allergic rhinitis, as evidenced by the total score of the quality-of-life questionnaire in patients with rhinoconjunctivitis. 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 alleviate symptoms in all urticarial conditions, 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. A reduction in itching by more than 50% was observed in 55% of patients receiving desloratadine, compared to 19% of patients receiving placebo. Treatment with desloratadine 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. Plasma concentrations of desloratadine are detectable within 30 minutes after administration; the drug 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 a dosing frequency of once daily. Bioavailability of desloratadine is dose-proportional within the range of 5 to 20 mg.

In a pharmacokinetic study where patient demographics were comparable to the general population with seasonal allergic rhinitis, approximately 4% of participants exhibited higher desloratadine concentrations; this percentage may vary depending on ethnic background. In these individuals, the maximum concentration at 7 hours was approximately 3 times higher, 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%). No evidence of clinically significant drug accumulation was observed after administration of desloratadine at doses of 5–20 mg once daily for 14 days.

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 and is neither a substrate nor an inhibitor of P-glycoprotein.

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

Patients with renal impairment. The pharmacokinetics of desloratadine in patients with chronic renal insufficiency were compared to those 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.

Clinical characteristics.

Indications.

Relief of symptoms associated with:

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

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 of desloratadine tablets, no clinically significant interactions were observed when co-administered 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 were reported during treatment with the medicinal product; therefore, caution should be exercised when consuming alcohol during desloratadine therapy.

Interaction studies were conducted only in adult patients.

Special precautions for use

Desloratadine-Teva should be used with caution in patients with severe renal impairment.

Desloratadine should be prescribed with caution to patients with a personal or family history of seizures, and in children who may be more susceptible to developing new seizure episodes during desloratadine treatment. Physicians should consider discontinuing desloratadine in patients who experience a seizure while taking the medication.

Use during pregnancy or breastfeeding

Pregnancy. Extensive data on the use of desloratadine during pregnancy (over 1,000 pregnancies resulting in live births) have not shown teratogenic, fetotoxic, or adverse effects on the fetus/newborn. Animal studies have not revealed any direct or indirect adverse effects on reproductive toxicity. As a precautionary measure, it is advisable to avoid using Desloratadine-Teva during pregnancy.

Breastfeeding. Desloratadine is excreted into breast milk. The effect of desloratadine on newborns/infants is unknown. Women who are breastfeeding are advised to weigh the necessity of discontinuing breastfeeding or avoiding the use of the drug, taking into account the benefits of breastfeeding for the child and the therapeutic benefits of the drug for the mother.

Fertility. There are no data available on the effects of desloratadine on male or female fertility.

Ability to affect reaction speed when driving or operating machinery

Clinical trial data indicate that Desloratadine-Teva has no effect or only a negligible effect on the ability to drive or operate machinery. Patients should be informed that most people do not experience drowsiness. However, since individual responses to any medication may vary, it is recommended that patients refrain from activities requiring mental alertness, such as driving a car or operating machinery, until they have determined how they individually respond to the medication.

Method of Administration and Dosage.

For adults and children aged 12 years and older: 1 tablet once daily, regardless of food intake, to relieve 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 upon symptom resolution and resume if symptoms reappear.

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 tablets in adolescents aged 12 to 17 years.

The efficacy and safety of 5 mg film-coated desloratadine tablets in children under 12 years of age have not been established.

Overdose.

Based on post-marketing data, the adverse reaction profile associated with overdose was similar to that of therapeutic doses, although the manifestations were more severe.

Treatment. In case of overdose, standard measures aimed at removing 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 studies with multiple doses 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 manifestations may be more severe.

Adverse reactions.

Summary of safety profile. In clinical trials for the indications including allergic rhinitis and chronic idiopathic urticaria, adverse reactions were reported in patients receiving 5 mg of desloratadine once daily 3% more frequently than in patients receiving placebo. The most commonly reported reactions, compared to the placebo group, were fatigue (1.2%), dry mouth (0.8%), and headache (0.6%).

Children. In clinical trials involving 578 children aged 12–17 years, the most commonly reported adverse reaction was headache, occurring in 5.9% of patients receiving desloratadine and 6.9% of patients receiving placebo.

Overall frequency of adverse reactions. Adverse reactions reported during clinical trials with a frequency higher than in the placebo group, as well as those reported during the post-marketing period, are classified as follows: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10000 to <1/1000), very rare (<1/10000), frequency not known (cannot be estimated from the available data).

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

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

Nervous system disorders. Common: headache. Very rare: dizziness, somnolence, insomnia, psychomotor hyperactivity, convulsions.

Eye disorders. Frequency not known: dry eyes.

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

Gastrointestinal disorders. Common: dry mouth. Very rare: abdominal pain, nausea, vomiting, dyspepsia, diarrhoea.

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. Common: fatigue. Very rare: hypersensitivity reactions (such as anaphylaxis, angioedema, dyspnoea, pruritus, rash, and urticaria). Frequency not known: asthenia.

Investigations. Frequency not known: weight increase.

Children. In the post-marketing period, other adverse reactions (frequency not known) have been reported: QT interval prolongation, arrhythmia, bradycardia, behavioural disturbances, and aggression.

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

In 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 incidence of seizure onset of 80.3 per 100,000 person-years. In 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 incidence of 36.4 per 100,000 person-years.

Shelf life. 3 years.

Storage conditions. The medicinal product does not require special storage conditions. Store in a place inaccessible to children.

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

Supply category. Over-the-counter.

Manufacturer. Actavis LTD.

Manufacturer's address and location of operations.

BLB015, BLB 016 Bulberr Industrial Building, Zebun ZTN 3000, Malta.