Edem

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

Composition:

Active substance: desloratadine;

1 tablet contains 5 mg of desloratadine calculated as anhydrous 100% substance;

Excipients: calcium hydrogen phosphate dihydrate, microcrystalline cellulose, lactose monohydrate, maize starch, hypromellose, calcium stearate, Opadry II 85F 30571 Blue (iron oxide red (E 172), polyvinyl alcohol, titanium dioxide (E 171), talc, indigo carmine (E 132), polyethylene glycol).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: round, biconvex film-coated tablets of blue color.

Pharmacotherapeutic group. Systemic antihistamines.

ATC code R06AX27.

Pharmacological properties.

Pharmacodynamics.

Desloratadine is a non-sedating, long-acting antihistamine that exerts selective antagonistic action on peripheral H1-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 where 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, administration of 45 mg daily (10 times the maximum recommended clinical daily dose) for 10 days did not result in QT interval prolongation.

In patients with allergic rhinitis, Edem® effectively relieved symptoms such as sneezing, nasal discharge, itching, eye irritation, tearing, redness, and palate itching. The drug effectively controlled symptoms for 24 hours.

Desloratadine barely penetrates the central nervous system. In controlled clinical trials, at the recommended daily dose of 5 mg, the incidence of drowsiness did not differ from the placebo group. In clinical studies, a single dose of desloratadine at 7.5 mg daily did not affect psychomotor performance.

The drug 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 of urticaria. Since histamine release is a causative factor in all forms of urticaria, desloratadine is expected to effectively relieve symptoms in other forms of urticaria besides chronic idiopathic urticaria.

In two placebo-controlled, 6-week studies involving patients with chronic idiopathic urticaria, desloratadine 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. Itching relief of more than 50% was observed in 55% of patients taking desloratadine, compared to 19% of patients taking placebo. The drug did not significantly affect sleep or daytime activity.

Pharmacokinetics.

Absorption.

Desloratadine plasma concentration can be detected within 30 minutes after drug administration. Desloratadine is well absorbed, with maximum concentration 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 dosing frequency (once daily). Desloratadine bioavailability was dose-proportional in the range of 5 to 20 mg.

In a pharmacokinetic study where patient demographics were comparable to the general group of patients with seasonal allergic rhinitis, 4% of participants showed higher desloratadine concentrations. This proportion may vary depending on ethnicity. Maximum desloratadine concentration was approximately 3 times higher at about 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 patient group.

Distribution.

Desloratadine is moderately bound to plasma proteins (83–87%). No evidence of clinically significant drug 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 interaction with other medicinal products cannot be completely ruled out. 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 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 or to any of the excipients of the medicinal product or to loratadine.

Interaction with other medicinal products and other forms of interaction.

In clinical studies of desloratadine in tablet form, no clinically significant interactions were observed when co-administered with erythromycin or ketoconazole.

According to clinical pharmacological studies, concomitant use of the drug with alcohol did not show any enhanced negative effect of ethanol on psychomotor function. However, during the post-marketing period, cases of alcohol intolerance and alcohol intoxication have been reported during use of the Edem® medication. Therefore, caution should be exercised when consuming alcohol during treatment with Edem®.

Special precautions for use.

In patients with severe renal impairment, the use of Edem® should be carried out under medical supervision.

Desloratadine should be used with caution in patients with a history of seizures or with inherited predisposition. In patients who experience a seizure during treatment, discontinuation of desloratadine should be considered.

This medication should not be taken by patients with rare hereditary disorders of galactose intolerance, lactase deficiency, or glucose-galactose malabsorption syndrome.

Use during pregnancy or breastfeeding.

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 Edem® is not recommended during pregnancy.

Breastfeeding period.

Desloratadine is excreted in breast milk; therefore, the use of Edem® is not recommended in breastfeeding women.

Ability to influence reaction rate while driving or operating machinery.

Desloratadine has no known effect on the ability to drive or operate machinery. However, patients should be informed that very rarely some individuals may experience drowsiness, which could affect their ability to drive or operate complex machinery.

Dosage and Administration.

Adults and children aged 12 years and older: 1 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 managed 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 continue throughout the entire period of allergen exposure.

Children.

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

Overdose.

In case of overdose, standard measures to remove the unabsorbed active substance should be applied. Symptomatic and supportive treatment 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 eliminated by hemodialysis. The possibility of its removal by peritoneal dialysis has not been established.

Adverse Reactions

In clinical studies of 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 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 studies involving 578 adolescents aged 12 to 17 years, the most commonly reported adverse reaction was headache, occurring in 5.9% of patients receiving 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, aggression, and agitation.

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 frequency not known (cannot be estimated from available data).

In the post-marketing period the following have been observed (frequency unknown): QT interval prolongation, arrhythmia, and bradycardia.

Shelf life.

3 years.

Do not use the medicinal product after the expiry date stated on the packaging.

Storage conditions.

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

Keep out of the reach of children.

Packaging. 10 or 30 tablets in a blister pack. 1 blister pack in a carton.

Category of release. Over-the-counter.

Manufacturer: JSC "Farmak".

Manufacturer's address and place of business.

74, Kyrylivska Street, Kyiv, 04080, Ukraine.