Astrya

INSTRUCTION for medical use of the medicinal product Astria® (Astria)

Composition:

Active substance: desloratadine;

1 tablet contains 5 mg of desloratadine;

Excipients: calcium hydrogen phosphate (anhydrous), microcrystalline cellulose, maize starch, talc, mixture of carnauba wax and white wax;

Coating: hypromellose, polyethylene glycol (macrogol) 6000, titanium dioxide (E 171); indigo carmine (E 132).

Pharmaceutical form. Film-coated tablets.

Main physicochemical characteristics: round, biconvex tablets coated with a blue or light-blue film coating.

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-receptors. After oral administration, desloratadine selectively blocks peripheral histamine H1-receptors.

In in vitro studies, desloratadine demonstrated anti-allergic 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, such as 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 pharmacological 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, itching, eye irritation, tearing, redness, and itching of the palate. Desloratadine provided effective symptom control for up to 24 hours.

Desloratadine barely penetrates the central nervous system. In controlled clinical trials, at the recommended dose of 5 mg daily, the incidence of somnolence did not differ from that in the placebo group. In clinical studies, a single dose of Astrea**®** at a daily dose of 7.5 mg had no effect on psychomotor performance.

Astrea**®** effectively reduced the severity of seasonal allergic rhinitis, as measured by the total rhinoconjunctivitis quality-of-life questionnaire score. 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 under 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, including chronic idiopathic urticaria.

In two placebo-controlled, 6-week studies involving patients with chronic idiopathic urticaria, the medicinal product Astrea**®** 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. Relief of itching by more than 50% was observed in 55% of patients receiving desloratadine, compared to 19% of patients receiving placebo. The drug had no significant impact on 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 corresponds to its half-life (approximately 27 hours) and the dosing frequency of once daily. Bioavailability of desloratadine was proportional to the dose 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 showed 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 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 breakfast) 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 and urticaria.

Contraindications.

Hypersensitivity to the active substance, to any excipient, 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 Astraea**®**.

Special precautions for use

In patients with severe renal impairment, the drug 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.

Use during pregnancy or breastfeeding.

Desloratadine did not show teratogenic effects in animal studies.

The safety of desloratadine use during pregnancy has not been established; therefore, the use of Astraea**®** film-coated tablets during pregnancy is not recommended.

Breastfeeding

Desloratadine passes into breast milk; therefore, the use of Astraea**®** 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: one 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 administered according to patient history: discontinue after symptoms resolve and resume 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 data on the efficacy of desloratadine in children aged 12 to 17 years (see section "Adverse reactions").

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

Overdose.

In case of overdose, standard measures should be taken to remove the unabsorbed active substance. Symptomatic and supportive therapy is recommended. In clinical studies where desloratadine was administered at doses of 45 mg (9 times the recommended dose), no clinically significant adverse reactions were observed. Desloratadine is not removed by hemodialysis; its elimination via peritoneal dialysis has not been established.

Adverse reactions

In clinical trials for the 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, occurring 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 the use of desloratadine, which may manifest as irritability and aggression, as well as agitation.

During 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 (≥ 1/10,000, < 1/1000), very rare (< 1/10,000), and not known.

Shelf life. 2 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C. Keep out of reach and sight of children.

Packaging.

10 tablets per blister; 1 or 3 blisters per carton;

30 tablets per blister; 1 or 3 blisters per carton.

Supply category.

Over-the-counter.

Marketing Authorization Holder: LLC "BAUM PHARM GMBH REPRESENTATION".

Address of the Marketing Authorization Holder: 66 Shyroka Street, Lviv, 79052, Ukraine.

Manufacturer:

LLC "ASTRAFARM", Ukraine.

Manufacturer's address and place of business:

6 Kyivska Street, Vyshneve, Bucha District, Kyiv Region, 08132, Ukraine.