Hitaxa

INSTRUCTIONS for medical use of the medicinal product Xitaxa (Xitaxa)

Composition:

Active substance: desloratadine;

1 ml of oral solution contains 0.5 mg desloratadine;

Excipients: hypromellose; sucralose; citric acid, monohydrate; sodium citrate; sorbitol solution, non-crystallizing (E 420); propylene glycol; flavouring; purified water.

Pharmaceutical form. Oral solution.

Main physicochemical properties: clear, colourless solution with a fruity taste.

Pharmacotherapeutic group.

Antihistamines for systemic use.

ATC code R06AX27.

Pharmacological Properties.

Pharmacodynamics.

Desloratadine is a potent, selective blocker of peripheral histamine H1-receptors that does not exhibit sedative effects. Desloratadine is the primary active metabolite of loratadine.

After oral administration, Hitax selectively blocks peripheral H1-histamine receptors, as the drug barely penetrates the blood-brain barrier.

Numerous studies have shown that, in addition to its antihistaminic activity, Hitax demonstrates anti-allergic and anti-inflammatory properties. It has been established that Hitax suppresses a cascade of various reactions underlying allergic inflammation, namely:

• release of pro-inflammatory cytokines, including IL-4, IL-6, IL-8, IL-13;
• release of pro-inflammatory 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 and allergic cough in animal studies.

The safety of Hitax in children has been demonstrated in three clinical trials. The drug was administered to children aged 6 months to 11 years who required antihistamine therapy, at daily doses of 1 mg (age group 6–11 months), 1.25 mg (age group 1–5 years), or 2.5 mg (age group 6–11 years). The treatment was well tolerated, as confirmed by clinical laboratory test results, vital function monitoring, and ECG data (including QT interval duration).

During clinical trials, daily administration of Hitax at doses up to 20 mg for 14 days was not associated with statistically or clinically significant cardiovascular changes. In a clinical-pharmacological study, administration of Hitax at 45 mg/day (9 times higher than the therapeutic dose) for 10 days did not cause QT interval prolongation.

Desloratadine barely penetrates the blood-brain barrier. At the recommended dose of 5 mg, the incidence of drowsiness did not exceed that in the placebo group. In clinical trials, Hitax did not affect psychomotor functions when doses up to 7.5 mg were administered.

In addition to the conventional classification of allergic rhinitis into seasonal and perennial forms, allergic rhinitis can alternatively be classified according to symptom duration as intermittent or persistent. Intermittent allergic rhinitis is defined as symptoms occurring for less than 4 days per week or less than 4 weeks. Persistent allergic rhinitis is characterized by symptoms occurring for 4 or more days per week or for more than 4 weeks.

The clinical efficacy of Hitax in the treatment of seasonal allergic rhinitis has been demonstrated in four placebo-controlled clinical trials using multiple dosing regimens.

In patients with allergic rhinitis, Hitax effectively relieved symptoms such as sneezing, nasal discharge and itching, as well as eye irritation, tearing, redness, and itching of the palate.

Pharmacokinetics.

Desloratadine is detectable in plasma within 30 minutes after administration. Hitax effectively controls symptoms for 24 hours. Desloratadine is well absorbed. Peak 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 dosing frequency (once daily). The bioavailability of desloratadine was dose-proportional in the range of 5 to 20 mg.

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

A low rate of desloratadine metabolism has been observed in approximately 8% of subjects, in whom a significant increase in plasma levels and prolonged elimination half-life were noted. The prevalence of reduced metabolism may be influenced by race. However, this is currently considered clinically irrelevant.

Cross-comparative bioequivalence studies at the same dose demonstrated bioequivalence between the tablet and syrup formulations of the drug.

Pharmacokinetic studies in pediatric practice showed that AUC and Cmax values of desloratadine (when administered at recommended doses) are comparable to those in adults receiving desloratadine syrup at a dose of 5 mg.

Study results indicate that desloratadine does not inhibit CYP3A4 or CYP2D6 and is neither a substrate nor an inhibitor of P-glycoprotein.

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 or to loratadine.

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 desloratadine distribution.

Effect on laboratory test results

Treatment with Hitaksa should be discontinued approximately 48 hours before skin testing, as antihistamines may prevent or reduce the manifestations of positive dermatological reactions to allergens.

Special precautions for use

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

The medicinal product Xytaxa oral solution should be used with caution in patients with severe renal impairment.

Use with caution in patients with a personal or family history of seizures, particularly in young children who may be more susceptible to seizures during treatment with desloratadine. Physicians may consider discontinuing desloratadine in patients who experience seizures during treatment.

Xytaxa contains sorbitol and therefore is not recommended for patients with rare hereditary fructose intolerance, glucose-galactose malabsorption syndrome, or sucrase-isomaltase deficiency. It may have a mild laxative effect. The energy value of sorbitol is 2.6 kcal per 1 g.

Propylene glycol may cause symptoms similar to those produced by alcohol consumption.

This medicinal product contains 1.26 mg of sodium per dose. Caution is advised when administering to patients on a sodium-restricted diet.

Use during pregnancy or breastfeeding

Extensive data on desloratadine use during pregnancy (over 1000 cases) indicate no evidence of teratogenic or 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 the medicinal product Xytaxa during pregnancy.

Desloratadine is excreted in breast milk. Therefore, breastfeeding women should decide whether to discontinue breastfeeding or to avoid using the medicinal product, taking into account the benefits of breastfeeding for the child and the therapeutic benefits of the drug for the mother.

Fertility
Data on the effect of desloratadine on fertility are lacking.

Ability to affect reaction speed when driving or operating machinery

Clinical study data indicate that Xytaxa 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. Individual responses to medicinal products may vary. Patients are advised not to engage in activities requiring mental alertness, such as driving a car or operating machinery, until they have determined how they individually respond to the medicinal product.

Dosage and Administration.

To relieve symptoms associated with allergic rhinitis (including intermittent and persistent forms) and urticaria, Hitaksa should be administered in the following doses:

Adults and children aged 12 years and older: 10 mL of solution (5 mg of desloratadine) once daily.

Children aged 6 to 11 years: 5 mL of solution (2.5 mg of desloratadine) once daily.

Children aged 1 to 5 years: 2.5 mL of solution (1.25 mg of 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.

Administration method.

The medication is taken orally, independent of food intake.

Children.

The efficacy and safety of Hitaksa oral solution in children under 1 year of age have not been established.

Overdose.

In case of overdose, standard measures aimed at removing the unabsorbed active substance should be implemented. Symptomatic and supportive therapy is recommended. Desloratadine is not removed by hemodialysis; it is unknown whether it is eliminated by peritoneal dialysis.

Adverse Reactions

During clinical trials for approved indications, including allergic rhinitis and chronic idiopathic urticaria, adverse events were reported in patients receiving a 5 mg daily dose 3% more frequently 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%). During clinical trials of Hitaxa 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 the use of desloratadine, which may manifest as irritability, aggression, and excitability.

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

Other adverse reactions, which have been 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, Hitaxa at a single daily dose of 7.5 mg showed no effect on psychomotor performance.

Shelf life.

3 years.

Storage conditions.

Special storage conditions are not required. Store in the original packaging.

Packaging.

Bottles of 60 ml, 120 ml, 150 ml, closed with a screw cap with child-resistant closure, supplied with a measuring spoon or dosing syringe, in a cardboard box.

Supply category.

Over-the-counter.

Manufacturer.

Famar A.V.E. Aulon Plant, Greece

Adamed Pharma S.A., Poland

Manufacturer's address and location of operations.

49 km National Road Athens-Lamia, Aulona Attica, 19011, Greece.

ul. Marsz. J. Piłsudskiego 5, 95–200 Pabianice, Poland