Alerdez

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ALE RDEZ (ALERDEZ)

Composition:

Active substance: desloratadine;

1 tablet contains desloratadine – 5 mg;

Excipients: calcium hydrogen phosphate, microcrystalline cellulose, maize starch, talc, magnesium stearate;

Transparent coating: hypromellose, polyethylene glycol 400;

Film coating: polyvinyl alcohol, polyethylene glycol 4000, talc, titanium dioxide (E 171), indigo carmine (E 132).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: blue, round, film-coated tablets with a biconvex surface.

Pharmacotherapeutic group. Antihistamines for systemic use.

ATC code R06A X27.

Pharmacological properties.

Pharmacodynamics.

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

In in vitro studies, desloratadine demonstrated anti-allergic and anti-inflammatory properties on 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 in which 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, ocular irritation, tearing, redness, and itching of the palate. Desloratadine provided effective symptom control for 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 did not differ 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 improved the severity of seasonal allergic rhinitis, as measured by the total score for assessing quality of life in rhinoconjunctivitis. 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 conditions. Since histamine release is a causative factor in all forms of urticaria, desloratadine is expected to effectively relieve symptoms in other forms of urticaria, apart from chronic idiopathic urticaria.

In two placebo-controlled, 6-week studies involving patients with chronic idiopathic urticaria, desloratadine effectively reduced itching and decreased 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. A reduction in itching by more than 50% 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.

Plasma concentrations of desloratadine can be detected within 30 minutes after administration. Desloratadine 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 corresponded to its half-life (approximately 27 hours) and the once-daily dosing regimen. The bioavailability of desloratadine was dose-proportional over 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. The maximum concentration was approximately 3 times higher at around 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 accumulation was observed after administration of desloratadine doses (5 to 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 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 meal) did not affect the pharmacokinetics of desloratadine. It has also been established that grapefruit juice does not affect the pharmacokinetics of desloratadine.

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 or to any of the excipients 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 have been reported while taking the drug. Therefore, caution should be exercised when consuming alcohol during treatment with desloratadine.

Special precautions for use.

In patients with severe renal insufficiency, the use of the medicinal product Alerdiz should be carried out under medical supervision.

Seizures

Desloratadine should be prescribed with caution to patients with a personal or family history of seizures, especially children, as they are more susceptible to developing new seizures during desloratadine treatment. Physicians should consider discontinuing desloratadine in patients who experience seizures while on treatment.

Use during pregnancy or breastfeeding.

Animal studies have not demonstrated teratogenic effects of desloratadine. However, since the safety of desloratadine use during pregnancy has not been established, its use during pregnancy is not recommended.

Desloratadine passes into breast milk; therefore, its use during breastfeeding is not recommended.

Ability to influence reaction speed when driving or operating machinery.

Clinical studies have not shown any negative effect of desloratadine on the ability to drive or operate machinery. Nevertheless, patients should be warned that in very rare cases somnolence may occur, which could affect their ability to drive or operate vehicles and complex machinery.

Dosage and Administration.

For adults and children aged 12 years and older: 1 tablet once daily, regardless of food intake, for the relief of symptoms of allergic rhinitis (including intermittent and persistent allergic rhinitis) and urticaria.

Treatment of intermittent allergic rhinitis (symptoms present for fewer than 4 days per week or fewer than 4 weeks) should be based on the patient's medical history until symptoms resolve and may be resumed upon their recurrence.

For persistent allergic rhinitis (symptoms present for more than 4 days per week or more than 4 weeks), treatment should be continued throughout the entire period of allergen exposure.

Children.

Limited clinical data are available on the use of desloratadine tablets in adolescents aged 12 to 17 years (see section "Adverse Reactions").

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

Overdose.

In case of overdose, standard measures should be taken to remove unabsorbed desloratadine. Symptomatic and supportive treatment is recommended. Clinical trial data indicate that administration of desloratadine at a dose of 45 mg (9 times the recommended dose) did not result in clinically significant adverse reactions.

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

Adverse Reactions

In clinical studies evaluating indications including allergic rhinitis and chronic idiopathic urticaria, adverse reactions were observed 3% more frequently in patients receiving a 5 mg daily dose compared to patients receiving placebo.

The most commonly reported adverse effects were fatigue (1.2%), dry mouth (0.8%), and headache (0.6%).

Children. In clinical studies involving 578 adolescents aged 12 to 17 years, the most common adverse effect was headache. It occurred in 5.9% of patients taking desloratadine and in 6.9% of patients receiving placebo.

There is a risk of psychomotor hyperactivity (abnormal behavior) associated with desloratadine use (which may manifest as irritability and aggression, as well as excitation).

Below are listed adverse reactions reported more frequently than with placebo, as well as other adverse reactions reported during the post-marketing period. 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 (cannot be estimated from available data).

Psychiatric disorders: very rare – hallucinations; frequency not known – aggression, abnormal behavior, depressive mood.

Nervous system disorders: common – headache; very rare – dizziness, somnolence, insomnia, psychomotor hyperactivity, seizures.

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, diarrhea.

Hepatobiliary disorders: very rare – increased liver enzyme levels, elevated bilirubin, hepatitis; frequency not known – jaundice.

Musculoskeletal and connective tissue disorders: very rare – myalgia.

Skin and subcutaneous tissue disorders: frequency not known – photosensitivity.

Eye disorders: frequency not known – dry eyes.

General disorders: common – increased fatigue; very rare – hypersensitivity reactions (such as anaphylaxis, angioedema, dyspnea, pruritus, rash, and urticaria); frequency not known – asthenia.

Metabolism and nutrition disorders: frequency not known – increased appetite, weight gain.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after a medicinal product is authorized is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, pharmacists, and patients or their legal representatives should report all suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life. 3 years.

Storage conditions.

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

Keep out of reach of children.

Packaging.

10 tablets in a blister pack, 1 blister pack in a carton.

Availability. Over-the-counter.

Manufacturer.

Public Joint-Stock Company "Scientific and Production Center "Borshchagov Chemical and Pharmaceutical Plant".

Manufacturer's address and location of operations.

17 Miru Street, Kyiv, 03134, Ukraine.