Desloratadine

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT DESLORATADINE (DESLORATADINE)

Composition:

Active substance: desloratadine;

One film-coated tablet contains 5 mg of desloratadine;

Excipients: calcium hydrogen phosphate dihydrate, microcrystalline cellulose, corn starch, talc, carnauba wax, white wax, lactose monohydrate, hypromellose, titanium dioxide (E 171), polyethylene glycol, indigo carmine (E 132).

Pharmaceutical form. Film-coated tablets.

Main physicochemical characteristics: round-shaped, film-coated tablets, blue in color, with convex upper and lower surfaces. When broken and examined under a magnifying lens, a core surrounded by a single continuous layer is visible.

Pharmacotherapeutic group.

Antihistamines for systemic use. Other antihistamines for systemic use. Desloratadine.

ATC code R06A X27.

Pharmacological properties.

Pharmacodynamics.

Desloratadine is a non-sedating, long-acting antihistamine with selective antagonistic activity at peripheral H1-receptors. After oral administration, desloratadine selectively blocks peripheral histamine H1-receptors.

In in vitro studies, desloratadine demonstrated anti-allergic and anti-inflammatory properties in endothelial cells. This was 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, including P-selectin. The clinical significance of these observations has yet to be confirmed.

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 a daily dose of 45 mg (10 times the maximum recommended clinical daily dose) for 10 days, no QT interval prolongation was observed.

In patients with allergic rhinitis, desloratadine effectively relieved symptoms such as sneezing, rhinorrhea, nasal itching, eye irritation, tearing, redness, and palatal itching. Desloratadine provided effective symptom control for 24 hours.

Desloratadine penetrates the central nervous system (CNS) to a minimal extent. In controlled clinical studies, at the recommended dose of 5 mg daily, the incidence of somnolence was not different from that in the placebo group. In clinical studies, a single dose of desloratadine at 7.5 mg daily did not affect psychomotor performance.

Desloratadine effectively reduced the severity of seasonal allergic rhinitis, as measured 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 was studied in a clinical model of urticaria. Since histamine release is a causative factor in all forms of urticaria, desloratadine is expected to effectively relieve symptoms in other forms of urticaria besides chronic idiopathic urticaria.

In two placebo-controlled, 6-week studies involving patients with chronic idiopathic urticaria, desloratadine effectively relieved itching and reduced the number and size of hives by the end of the first dosing interval. In each study, the effect lasted throughout the 24-hour dosing interval. Itching relief of more than 50% was observed in 55% of patients taking desloratadine, compared to 19% of patients taking placebo.

The drug does not significantly affect sleep or daytime activity.

Pharmacokinetics.

Absorption.

Plasma concentrations of desloratadine can be detected 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 the once-daily dosing regimen. Desloratadine bioavailability was dose-proportional over the range of 5 to 20 mg.

In a pharmacokinetic study with demographic data comparable to the general population with seasonal allergic rhinitis, approximately 4% of participants exhibited higher desloratadine concentrations. This proportion may vary depending on ethnicity. Maximum desloratadine concentration was approximately 3 times higher at about 7 hours, and the terminal elimination half-life was approximately 89 hours. The safety profile in these patients did not differ 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 when desloratadine (5 to 20 mg) was administered 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 demonstrated that the drug does not inhibit CYP2D6, nor is it a substrate or inhibitor of P-glycoprotein.

Excretion.

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.

Clinical characteristics.

Indications.

Relief of symptoms associated with:

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

Contraindications.

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

Interaction with other medicinal products and other forms of interaction.

In clinical studies with desloratadine tablets, no clinically significant interactions were observed when co-administered with erythromycin or ketoconazole.

In clinical pharmacological studies, no enhancement of the negative effect of ethanol on psychomotor function was observed when the drug was administered together with alcohol. However, during the post-marketing period, cases of alcohol intolerance and alcohol intoxication during desloratadine use have been reported. Therefore, caution should be exercised when consuming alcohol during treatment with this medicinal product.

Since the enzyme responsible for desloratadine metabolism has not been identified, interactions with other medicinal products cannot be completely ruled out.

Special precautions for use.

The use of the drug in patients with severe renal impairment should be carried out under medical supervision.

Desloratadine should be administered with caution to patients who have a 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 therapy in patients who experience a seizure while taking the drug.

Patients with rare hereditary conditions of galactose intolerance, lactase deficiency, or glucose-galactose malabsorption should not take this medication.

Use during pregnancy or breastfeeding.

Desloratadine did not show teratogenic effects in animal studies.

The safety of the drug during pregnancy has not been established; therefore, desloratadine is not recommended during pregnancy.

Breastfeeding.

Desloratadine passes into breast milk; therefore, the use of the drug is not recommended in breastfeeding women.

Ability to affect reaction speed while driving or operating machinery.

In clinical studies assessing the ability to drive, no impairments were observed in patients taking desloratadine. However, patients should be informed about the possibility of experiencing somnolence, which may affect their ability to drive or operate complex machinery.

Method of Administration and Dosage

The medication is taken orally.

For adults and children aged 12 years and older, the recommended dose is 1 tablet (5 mg) 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 fewer than 4 days per week or fewer than 4 weeks) should be based on patient history: treatment should be discontinued once symptoms resolve and resumed upon their recurrence.

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

There are limited clinical data on the efficacy of desloratadine tablets in adolescents aged 12 to 17 years (see section "Adverse Reactions").

The efficacy and safety of the medication have not been established in children under 12 years of age.

Desloratadine may be used in children aged 12 years and older only after consultation with a physician.

Overdose

In case of overdose, standard measures aimed at removing the unabsorbed active substance should be implemented, along with symptomatic treatment.

When desloratadine was administered at doses up to 45 mg (9 times higher than the recommended dose) in clinical studies involving adults and adolescents, no clinically significant effects were observed.

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

Adverse Reactions

In clinical trials for the approved indications, including allergic rhinitis and chronic idiopathic urticaria, adverse events were reported 3% more frequently in patients receiving a 5 mg daily dose compared to patients receiving placebo.

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

Children. In clinical trials involving 578 adolescents aged 12 to 17 years, the most commonly reported adverse reaction was headache, observed in 5.9% of patients receiving desloratadine and in 6.9% of patients 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 nervousness.

In the post-marketing period, the following have been observed (frequency unknown): QT interval prolongation, arrhythmias, and bradycardia.

Summary table of adverse reaction frequencies.

The frequency of adverse reactions is classified as follows: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare (<1/10000), and frequency not known.

Shelf life. 2 years.

Storage conditions.

In the original packaging at a temperature not exceeding 25 °C. Keep out of reach of children.

Packaging.

10 tablets in a blister; 1, 2, 3, or 10 blisters per cardboard box.

Category of release.

Over-the-counter.

Manufacturer.

JSC "Tekhnolog".

Manufacturer's address and place of business.

8, Stara Prorina Street, Uman, Cherkasy region, Ukraine, 20300.