Lordes®

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT LORDES®

Composition:

Active substance: desloratadine;

2.5 mg of desloratadine in 5 ml of syrup;

Excipients: propylene glycol, anhydrous citric acid; sodium citrate, sodium benzoate (E 211), disodium edetate, sucrose, sorbitol (E 420), sunset yellow FCF (E 110), flavour "Tutti Frutti AG7322", purified water.

Pharmaceutical form. Syrup.

Main physicochemical characteristics: orange-colored liquid with characteristic odor.

Pharmacotherapeutic group.

Antihistamines for systemic use. ATC code R06AX27.

Pharmacological properties.

Pharmacodynamics.

Desloratadine is a selective antagonist of peripheral histamine H1-receptors and does not exhibit sedative effects. Desloratadine is the primary active metabolite of loratadine. After oral administration, desloratadine selectively blocks peripheral H1-histamine receptors and does not cross the blood-brain barrier.

In addition to its antihistaminic activity, desloratadine exerts antiallergic and anti-inflammatory effects.

It has been established that desloratadine inhibits a cascade of various reactions underlying the development of allergic inflammation, namely:

• release of proinflammatory cytokines, including IL-4, IL-6, IL-8, IL-13;
• release of proinflammatory chemokines, such as RANTES;
• production of superoxide anion by activated polymorphonuclear neutrophils;
• adhesion and chemotaxis of eosinophils;
• expression of adhesion molecules, such as P-selectin;
• IgE-dependent release of histamine, prostaglandin D2, and leukotriene C4;
• acute allergic bronchospasm in animal studies.

Pharmacokinetics.

Desloratadine does not cross the blood-brain barrier and does not affect psychomotor function at doses up to 7.5 mg.

Desloratadine becomes detectable in blood plasma within 30 minutes after administration.

Maximum plasma concentration of desloratadine is reached on average within 3 hours; the elimination half-life averages 27 hours. The extent of desloratadine accumulation corresponds to its half-life (approximately 27 hours) and the frequency of dosing (once daily). The bioavailability of desloratadine is proportional to the dose in the range of 5 to 20 mg.

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

Food (high-fat, high-calorie meal) or grapefruit juice does not affect the distribution of desloratadine.

Clinical characteristics.

Indications.

• For relief of symptoms associated with allergic rhinitis, such as sneezing, nasal discharge, itching, swelling and nasal congestion, as well as eye itching and redness, tearing, itching of the palate, and cough;
• for relief of symptoms associated with urticaria, such as itching and rash.

Contraindications.

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

Interaction with other medicinal products and other forms of interaction.

No clinically significant changes in plasma concentrations of desloratadine were observed during repeated co-administration with ketoconazole, erythromycin, azithromycin, fluoxetine, or cimetidine. Since the enzyme responsible for desloratadine metabolism has not been identified, interactions with other medicinal products cannot be completely excluded.

Food (high-fat, high-calorie meal) or grapefruit juice do not affect the distribution of desloratadine.

Effect on laboratory test results

Administration of Lordes® should be discontinued approximately 48 hours prior to skin testing, as antihistamines may prevent or reduce the manifestation of positive dermatological reactions to allergens.

Special precautions for use.

During clinical pharmacological studies, desloratadine did not enhance alcohol-induced effects such as impairment of psychomotor function and drowsiness. Results of psychomotor performance tests did not significantly differ between patients receiving desloratadine and those receiving placebo, either alone or in combination with alcohol.

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

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

If intolerance to certain sugars has been diagnosed, consult a physician before taking this medicinal product. LorDes® contains sucrose and sorbitol; therefore, patients with fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase deficiency should not take this product.

Sorbitol (E 420). If intolerance to certain sugars has been diagnosed, consult a physician before taking this medicinal product. May have a mild laxative effect. The energy value of 1 g of sorbitol is 2.6 kcal.

Yellow FCF (E 110). May cause allergic reactions.

This medicinal product contains 6.86 mg/mL of sodium. Caution is advised when administering to patients on a sodium-restricted diet.

Use during pregnancy or breastfeeding.

Extensive data on the use of desloratadine during pregnancy (over 1,000 cases) indicate no teratogenic, 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 LorDes® during pregnancy.

Desloratadine passes into breast milk; therefore, breastfeeding women should decide whether to discontinue breastfeeding or avoid using the drug, taking into account the benefits of breastfeeding for the infant and the therapeutic benefit of the drug for the mother.

Fertility. Data regarding effects on fertility are lacking.

Ability to influence reaction rate when driving or operating machinery.

Clinical trial data indicate that LorDes® has no effect or a negligible effect on the ability to drive or operate machinery. Patients should be informed that most people do not experience drowsiness. Individual responses to medicinal products may vary. Patients are advised not to engage in activities requiring concentration, such as driving a car or operating machinery, until they have determined their individual response to the medicinal product.

Dosage and Administration

Lordes®, syrup, should be taken regardless of food intake in the following doses:

Adults and children aged 12 years and older:

10 mL of syrup (5 mg desloratadine) once daily.

Treatment of intermittent allergic rhinitis (symptoms present for less than 4 days per week or less than 4 weeks) should be based on patient history: treatment should be discontinued after symptoms resolve and 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:

Aged 6 to 11 months – 2 mL of syrup (1 mg desloratadine) once daily;
Aged 1 to 5 years – 2.5 mL of syrup (1.25 mg desloratadine) once daily;
Aged 6 to 11 years – 5 mL of syrup (2.5 mg desloratadine) once daily.

The drug is not recommended for children under 6 months of age for the treatment of chronic idiopathic urticaria, and for children under 12 months of age for the treatment of allergic rhinitis.

Children.

The efficacy and safety of desloratadine syrup in children under 6 months of age have not been established.

Overdose.

In clinical trials, administration of desloratadine at doses up to 45 mg (9 times higher than the recommended dose) in adults and adolescents did not result in clinically significant effects; however, an increase in adverse effects is possible.

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

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

Adverse Reactions

During clinical trials for approved indications, including allergic rhinitis and chronic idiopathic urticaria, adverse effects were reported 3% more frequently in patients receiving a 5 mg daily dose compared to those receiving placebo. The most commonly reported adverse effects, compared to placebo, were fatigue (1.2%), dry mouth (0.8%), and headache (0.6%). During clinical studies of Lordest® in children aged 2 to 11 years, the incidence of adverse reactions was similar in both the syrup and placebo groups. In children aged 6 to 23 months, the most commonly reported adverse events (compared to placebo) were diarrhea (3.7%), fever (2.3%), and insomnia (2.3%).

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

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

Other adverse reactions, very rarely reported during the postmarketing period, are listed in the table 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.

Desloratadine hardly penetrates into the central nervous system. When used at the recommended adult dose of 5 mg, no increase in the incidence of drowsiness was observed compared to the placebo group. In clinical studies, Lordes® administered at a single daily dose of 7.5 mg did not affect psychomotor performance.

Shelf life.

2 years.

After first opening, store the syrup for up to 6 months.

Storage conditions.

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

Keep out of reach of children.

Packaging.

150 ml in a bottle. Each bottle comes with a plastic measuring spoon, packed in a cardboard box.

Supply category.

Over-the-counter (without prescription).

Manufacturer.

NOBEL ILAC SANAYI VE TICARET A.S.

Manufacturer's address and location of business activity.

Sankaklar Quarter, Eskikaraçay Street No:299, 81100 Düzce, Turkey.