Dezradin

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Desradin® (Desradin®)

Composition:

Active substance: desloratadine;

One film-coated tablet contains 5 mg of desloratadine;

Excipients: microcrystalline cellulose, hypromellose, hydrochloric acid, sodium hydroxide, corn starch (dried), lactose monohydrate, talc, macrogol 400, titanium dioxide (E 171), indigocarmine (E 132).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: blue, round, film-coated tablets with bevelled edges.

Pharmacotherapeutic group. Antihistamines – H1-receptor antagonists.

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. Desloratadine is the primary active metabolite of loratadine.

In in vitro studies, desloratadine demonstrated anti-allergic properties in endothelial cells. This was manifested by inhibition of the release of pro-inflammatory cytokines such as IL-4, IL-6, IL-8, and IL-13 from human mast cells/basophils, as well as inhibition of expression of adhesion molecules such as P-selectin. The clinical significance of these observations remains to be confirmed.

Numerous studies have shown that, in addition to its antihistaminic activity, the drug exerts anti-allergic and anti-inflammatory effects.

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.

The drug does not cross the blood-brain barrier. It has no effect on the cardiovascular system and does not cause QT interval prolongation on ECG. It does not affect the central nervous system, does not slow psychomotor reaction speed, and does not cause sedative effects. It prevents the development and alleviates the course of allergic reactions, exerting anti-pruritic and anti-exudative action (reduces capillary permeability, prevents tissue edema and smooth muscle spasm).

Desloratadine does not penetrate into the central nervous system and does not affect psychomotor function.

In patients with allergic rhinitis, desloratadine effectively relieved symptoms such as sneezing, rhinorrhea, and pruritus, as well as eye irritation, lacrimation, redness, and itching of the palate. Desloratadine effectively controlled symptoms for 24 hours.

Pharmacokinetics.

Absorption

Desloratadine plasma concentrations 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 once-daily dosing regimen. Desloratadine bioavailability was dose-proportional over the range of 5 to 20 mg.

In a pharmacokinetic study where patient demographics were compared with the general population of seasonal allergic rhinitis patients, approximately 4% of subjects showed higher desloratadine concentrations. This percentage may vary depending on ethnic background. The maximum concentration of desloratadine was approximately 3 times higher, reached about 7 hours post-dose, with a terminal elimination half-life of approximately 89 hours. The safety profile in these subjects was not different from that of 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 ruled out. Desloratadine does not inhibit CYP3A4 in vivo. In vitro studies have demonstrated that the drug is neither an inhibitor nor a substrate of CYP2D6, nor an inhibitor or substrate of P-glycoprotein.

Elimination.

In a single-dose study of desloratadine 7.5 mg, food (high-fat, high-calorie breakfast) had no effect on the pharmacokinetics of desloratadine. In another study, grapefruit juice was shown to have no effect on 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, or to loratadine.

Interaction with other medicinal products and other forms of interaction.

In clinical studies, no clinically significant interactions were observed when desloratadine tablets were co-administered with erythromycin or ketoconazole (see section "Pharmacodynamics").

Children.

Interaction studies were conducted in adult patients.

In clinical pharmacological studies, no enhancement of the negative effect of ethanol on performance reduction was observed when the drug was used concomitantly with alcohol (see section "Pharmacodynamics"). However, during the post-marketing period, cases of alcohol intolerance and alcohol intoxication were reported during the use of the drug. Therefore, caution should be exercised when co-administering with alcohol.

Special precautions for use

In patients with severe renal impairment, the drug should be administered under medical supervision (see section "Pharmacokinetics").

Desloratadine should be used with caution in patients with a history or family history of seizures, particularly in children (see section "Adverse reactions"), who may be more susceptible to developing a new seizure during treatment with desloratadine. Physicians should consider discontinuing desloratadine treatment in patients who experience a seizure while taking the drug.

Special warnings regarding excipients

Desradin® contains lactose. Patients with rare hereditary galactose intolerance, lactase deficiency, or glucose-galactose malabsorption syndrome should not take this medication.

Use during pregnancy or breastfeeding

Pregnancy

Desloratadine did not show teratogenic effects in animal studies.

The safety of using the drug during pregnancy has not been established; therefore, the use of this medicinal product during pregnancy is not recommended.

Breastfeeding

Desloratadine passes into breast milk; therefore, the use of this medicinal product is not recommended in women who are breastfeeding.

Fertility

There are no available data on the effects on fertility in men or women.

Ability to affect reaction speed when driving or operating machinery

Desloratadine has no effect or has a negligible effect on the ability to drive or operate machinery based on clinical trials. Patients should be informed that most people do not experience drowsiness. However, since individual responses to any medication may vary, it is recommended to advise patients not to engage in activities requiring mental alertness, such as driving a car or operating machinery, until they have determined how they personally respond to the drug.

Dosage and Administration

Adults and children aged 12 years and older

The recommended dose of Desradin® is 1 tablet once daily.

Treatment of intermittent allergic rhinitis (symptoms present for fewer than 4 days per week or for fewer than 4 weeks) should be administered according to the patient's medical history until symptoms resolve and may be resumed upon their recurrence. For treatment of persistent allergic rhinitis (symptoms present for more than 4 days per week or for more than 4 weeks), prolonged treatment during allergen exposure periods may be recommended for patients.

Administration

The medication should be taken orally, independent of food intake.

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

Overdose

Children and adult patients

The adverse reaction profile associated with overdose observed during post-marketing use is similar to that seen with therapeutic doses, although effects may be more pronounced.

Treatment

In case of overdose, standard measures should be applied to remove the unabsorbed active substance. Symptomatic and supportive treatment is recommended.

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

Symptoms

In clinical studies where desloratadine was administered at doses of 45 mg (9 times the recommended dose), no clinically significant adverse reactions were observed.

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 compared to those 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 those 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.

Other adverse reactions reported during the post-marketing period in children, with unknown frequency, included 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 (≥1/1,000, <1/100), rare (≥1/10,000, <1/1,000), very rare (<1/10,000), and frequency not known.

Metabolism and nutrition disorders:

Frequency not known: Increased appetite.

Psychiatric disorders:

Very rare: Hallucinations;

Frequency not known: Abnormal behavior, aggression, depressed mood.

Nervous system disorders:

Common: Headache;

Very rare: Dizziness, somnolence, insomnia, psychomotor hyperactivity, convulsions.

Eye disorders:

Frequency not known: Dry eyes.

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 enzymes, elevated bilirubin, hepatitis;

Frequency not known: Jaundice.

Musculoskeletal and connective tissue disorders:

Very rare: Myalgia.

Skin and subcutaneous tissue disorders:

Frequency not known: Photosensitivity.

General disorders and administration site conditions:

Common: Fatigue;

Very rare: Hypersensitivity reactions (such as anaphylaxis, Quincke's edema, dyspnea, pruritus, rash, and urticaria);

Frequency not known: Asthenia.

Investigations:

Frequency not known: Weight gain.

A retrospective observational safety study revealed an increased incidence of new-onset seizures in patients aged 0 to 19 years during desloratadine use compared to periods when they were not taking desloratadine.

Among children aged 0–4 years, the adjusted absolute increase was 37.5 (95% confidence interval (CI) 10.5–64.5) per 100,000 person-years (PY), with a baseline seizure incidence of 80.3 per 100,000 PY. Among patients aged 5–19 years, the adjusted absolute increase was 11.3 (95% CI 2.3–20.2) per 100,000 PY, with a baseline incidence of 36.4 per 100,000 PY (see section "Special precautions for use").

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after medicine authorization is of great importance. It allows continuous monitoring of the benefit-risk balance of the medicine. Healthcare professionals are required to report any suspected adverse reactions via the national reporting system.

Shelf life.

5 years.

Storage conditions.

Store at temperatures not exceeding 30 °C in the original packaging to protect from moisture. Keep out of reach of children.

Packaging.

10 tablets per blister; 1 or 3 blisters per cardboard box.

Prescription status. Over-the-counter.

Manufacturer.

KRKA, d.d., Novo mesto, Slovenia.

Manufacturer's address and location of operations.

Smarjeska cesta 6, 8501 Novo mesto, Slovenia.