Desloratadine

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

Composition:

active substance: desloratadine;

1 tablet contains 5 mg of desloratadine;

excipients: calcium hydrogen phosphate; magnesium stearate; microcrystalline cellulose; lactose monohydrate; hypromellose; corn starch; titanium dioxide (E 171); indigocarmine (E 132).

Pharmaceutical form. Film-coated tablets.

Main physicochemical characteristics: film-coated tablets, blue in color, round-shaped, biconvex. Two layers are visible in cross-section.

Pharmacotherapeutic group. Antihistamines for systemic use. ATC code R06AX27.

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 has demonstrated anti-allergic and anti-inflammatory properties in 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, including P-selectin. The clinical relevance 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 daily clinical dose) for 10 days, no QT interval prolongation was observed.

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

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

Desloratadine effectively improved the severity of seasonal allergic rhinitis, as measured by the total score of the rhinoconjunctivitis quality-of-life questionnaire. The greatest improvements were observed in questionnaire items related to practical problems and daily activities limited by symptoms.

Chronic idiopathic urticaria has been 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, including 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 within the first dosing interval. In each study, the effect lasted throughout the 24-hour dosing interval. More than 50% reduction in itching was observed in 55% of patients taking desloratadine, compared to 19% of patients receiving placebo. The drug did not significantly affect sleep or daytime activity.

Pharmacokinetics

Absorption.

Desloratadine plasma concentrations can be detected within 30 minutes after administration. Desloratadine is well absorbed, with peak plasma 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 once-daily dosing frequency. The bioavailability of desloratadine was dose-proportional in 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 proportion may vary depending on ethnic background. Maximum desloratadine concentration was approximately 3 times higher at around 7 hours, and the terminal half-life was approximately 89 hours. The safety profile in these patients was comparable to that in the general population.

Distribution.

Desloratadine is moderately bound to plasma proteins (83–87%). No evidence of clinically significant accumulation 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 is neither an inhibitor nor a substrate of CYP2D6 or P-glycoprotein.

Excretion.

In a single-dose study of desloratadine 7.5 mg, food intake (a high-fat, high-calorie meal) 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 the active substance, to any of the excipients 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 negative effect of ethanol on psychomotor function was observed when the drug was used concomitantly with alcohol. However, during the post-marketing period, cases of alcohol intolerance and alcohol intoxication during the use of the drug have been reported. Therefore, caution should be exercised when consuming alcohol during treatment with Desloratadine.

Special precautions for use

In patients with severe renal impairment, Desloratadine should be administered under medical supervision.

Desloratadine should be prescribed with caution to patients who have a history of seizures. Children may be more susceptible to developing a new seizure during desloratadine treatment. The physician must decide whether to discontinue desloratadine therapy in patients who experience a seizure while taking the drug.

The product contains lactose. If the patient has been diagnosed with an intolerance to certain sugars, medical advice should be sought before taking this medicinal product.

Use during pregnancy or breastfeeding

Desloratadine showed no teratogenic effects in animal studies.

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

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

Ability to affect reaction speed when 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 that, very rarely, some individuals may experience drowsiness, which could affect their ability to drive or operate complex machinery.

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 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 desloratadine tablets in children under 12 years of age have not been established.

Overdose.

In case of overdose, standard measures to remove unabsorbed active substance should be applied. Symptomatic and supportive treatment is recommended. In clinical studies, where desloratadine was administered at doses of 45 mg (9 times higher than the recommended dose), no clinically significant adverse reactions were observed. Desloratadine is not removed by hemodialysis; its elimination 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 than in 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. It occurred in 5.9% of patients treated with 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, aggression, and agitation.

In the post-marketing period, the following events have been observed (frequency unknown): QT interval prolongation, arrhythmia, 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 (≥1/10,000, <1/1000), very rare (<1/10,000), frequency not known (cannot be estimated from the available data).

Shelf life. 2 years.

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

Keep out of reach of children.

Packaging. Tablets, 10 pcs in a blister pack in a box.

Prescription status. Over-the-counter.

Manufacturer: LIMITED LIABILITY COMPANY "CORPORATION "ZDOROV'YA".

Manufacturer's address and place of business.

Ukraine, 61013, Kharkiv region, city of Kharkiv, Shevchenko street, building 22.