Lordestin^® (Tablets, Syrup) Instructions for Use

ATC Code

R06AX27 (Desloratadine)

Active Substance

Desloratadine (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Histamine H₁-receptor blocker. Antiallergic drug

Pharmacotherapeutic Group

Antiallergic agent – H₁-histamine receptor blocker

Pharmacological Action

Desloratadine is a long-acting histamine antagonist. It is the primary active metabolite of loratadine.

It inhibits a whole cascade of allergic inflammation reactions, including the release of pro-inflammatory cytokines such as interleukins IL-4, IL-6, IL-8, and IL-13, the release of pro-inflammatory chemokines (RANTES), the production of superoxide anions by activated polymorphonuclear neutrophils, eosinophil chemotaxis and adhesion, the release of adhesion molecules such as P-selectin, and IgE-dependent release of histamine, prostaglandin D2, and leukotriene C4.

Thus, Desloratadine prevents the development and alleviates the course of allergic reactions, and also has antipruritic and anti-exudative effects, reduces capillary permeability, and prevents the development of tissue edema and smooth muscle spasm.

The drug does not affect the central nervous system, practically does not have a sedative effect (does not cause drowsiness) and does not affect the speed of psychomotor reactions.

In clinical and pharmacological studies of the use of desloratadine at the recommended therapeutic dose, no prolongation of the QT interval on the ECG was noted.

The action of desloratadine begins within 30 minutes after oral administration and lasts for 24 hours.

Pharmacokinetics

Absorption

Desloratadine is well absorbed from the gastrointestinal tract. It is detected in blood plasma 30 minutes after oral administration.

C_max in blood plasma is reached, on average, 3 hours after administration.

Distribution

It does not penetrate the blood-brain barrier. Plasma protein binding is 83-87%.

When used in adults and adolescents for 14 days at doses from 5 mg to 20 mg once daily, no clinically significant accumulation of the drug was noted.

Concomitant intake of food or grapefruit juice did not affect the distribution of desloratadine when used at a dose of 7.5 mg once daily.

Metabolism

Desloratadine is not an inhibitor of CYP3A4 and CYP2D6 isoenzymes and is not a substrate or inhibitor of P-glycoprotein.

It is intensively metabolized in the liver by hydroxylation to form 3-OH-desloratadine glucuronide.

Excretion

Only a small part of the orally administered dose is excreted unchanged by the kidneys (<2%) and through the intestines (<7%).

T_1/2 is 20-30 hours (on average – 27 hours).

Indications

• Allergic rhinitis (relief or elimination of sneezing, nasal congestion, nasal discharge, nasal itching, itching of the palate, redness and itching of the eyes, lacrimation);
• Urticaria (reduction or elimination of skin itching, rash).

ICD codes

Dosage Regimen

Tablets

Orally. It is recommended to take the drug at the same time of day, regardless of meals, with a small amount of water.

The tablet should be swallowed whole, without chewing.

Adults

Adults aged 18 years and older are prescribed the drug once daily at a dose of 5 mg (1 film-coated tablet).

For seasonal (intermittent) allergic rhinitis (presence of symptoms for less than 4 days per week or less than 4 weeks per year), the course of the disease should be assessed taking into account the medical history.

If symptoms disappear, treatment may be discontinued and resumed upon their reappearance.

For perennial (persistent) allergic rhinitis (presence of symptoms for 4 or more days per week or more than 4 weeks per year), the drug should be taken throughout the period of allergen exposure.

Children

The dosage regimen for children aged 12 to 18 years does not differ from the dosage regimen for adults.

Lordestin^® should not be prescribed to children from 0 to 12 years, as the safety and efficacy of desloratadine 5 mg, film-coated tablets, in children under 12 years of age have not been established.

Data are not available.

Syrup

Orally. The syrup should be taken regardless of meals, with a small amount of water.

Children aged 1 to 5 years 1.25 mg (2.5 ml of syrup) once daily.

Children aged 6 to 11 years 2.5 mg (5 ml of syrup) once daily.

Adults and adolescents from 12 years 5 mg (10 ml of syrup) once daily.

For correct dosing, use the supplied plastic dosing cup, graduated from 2.5 ml to 20 ml.

If improvement does not occur after treatment, or symptoms worsen, or new symptoms appear, it is necessary to consult a doctor.

The drug should be used only according to those indications, method of application, and in those doses that are indicated in the instructions.

Adverse Reactions

In children aged 6 to 23 months, the following side effects were noted, the frequency of which was somewhat higher than with placebo: diarrhea (in 3.7% of cases), increased body temperature (2.3%), insomnia (2.3%).

In children aged 2 to 11 years, when using desloratadine syrup, the frequency of side effects was the same as with placebo.

According to the results of clinical studies in children aged 6 to 11 years, when taking desloratadine syrup at recommended doses (2.5 mg/day), no side effects were identified.

In children aged 12-17 years, according to the results of clinical studies, the most common side effect was headache (5.9%), the frequency of which was not higher than with placebo (6.9%).

In adults and adolescents (12 years and older), according to the results of clinical studies, side effects were recorded in 3% of patients compared to the placebo group, among which the most frequently noted were: increased fatigue (1.2%), dry mouth (0.8%), headache (0.6%).

Information on side effects is provided based on the results of clinical studies and post-registration surveillance data.

According to WHO, side effects are classified according to their frequency of occurrence as follows: very common (≥1/10), common (from ≥1/100 to <1/10), uncommon (from ≥1/1000 to <1/100), rare (from ≥1/10,000 to <1/1000), very rare (<1/10,000); frequency unknown – from the available data it was not possible to establish the frequency of occurrence.

Psychiatric disorders very rare – hallucinations; frequency unknown – abnormal behavior, aggression.

Nervous system disorders: common – headache, insomnia (in children under 2 years); very rare – dizziness, drowsiness, insomnia, psychomotor hyperactivity, convulsions.

Hepatobiliary disorders very rare – increased activity of liver enzymes, increased bilirubin concentration, hepatitis; frequency unknown – jaundice.

Gastrointestinal disorders: common – dry mouth, diarrhea (in children under 2 years); very rare – abdominal pain, nausea, vomiting, dyspepsia, diarrhea.

Cardiac disorders very rare – tachycardia, palpitations; frequency unknown – QT interval prolongation.

Musculoskeletal and connective tissue disorders very rare – myalgia.

Skin and subcutaneous tissue disorders frequency unknown – photosensitivity.

General disorders and administration site conditions common – increased fatigue, fever (in children under 2 years); very rare – anaphylaxis, angioedema, dyspnea, itching, rash, including urticaria; frequency unknown – asthenia.

Post-registration period

Children frequency unknown – QT interval prolongation, arrhythmia, bradycardia, abnormal behavior, aggression.

If any of the side effects listed in the instructions worsen, or the patient notices any other side effects not listed in the instructions, they should inform their doctor.

Contraindications

• Hypersensitivity to desloratadine, loratadine or any other component of the drug;
• Pregnancy;
• Breastfeeding period;
• Age under 1 year (for this dosage form);
• Hereditary disorders – sorbitol intolerance or malabsorption, sorbitol dehydrogenase deficiency (Lordestin^® syrup 0.5 mg/ml contains sorbitol; sorbitol intolerance or malabsorption is often accompanied by intolerance to other sugars, for example, fructose).

With caution: severe renal impairment, history of convulsions.

Use in Pregnancy and Lactation

The use of the drug in pregnant women is contraindicated due to the lack of clinical data on the safety of using Lordestin^® syrup 0.5 mg/ml during pregnancy.

Desloratadine is excreted in breast milk, therefore the use of Lordestin^® syrup 0.5 mg/ml during breastfeeding is contraindicated.

Use in Renal Impairment

Use the drug with caution in patients with severe renal impairment.

Pediatric Use

The use of the drug is contraindicated in children under 1 year of age.

Special Precautions

The shelf life of the drug after first opening the bottle is 28 days.

Use in children

The efficacy and safety of using Lordestin^® syrup in children under 1 year of age have not been established.

No studies have been conducted on the efficacy of desloratadine in rhinitis of infectious etiology.

Severe renal impairment

In patients with severe renal impairment or on hemodialysis, the plasma concentration of desloratadine increases by 1.7 and 2.5 times, respectively.

A minimal change in the concentration of 3-hydroxydesloratadine was detected.

Desloratadine and 3-hydroxydesloratadine are poorly removed by dialysis.

Renal impairment does not affect the binding of desloratadine and 3-hydroxydesloratadine to plasma proteins.

Based on the pharmacokinetics of Lordestin^® syrup 0.5 mg/ml, caution should be exercised when using the drug in patients with renal impairment.

History of convulsions

Caution should be exercised when using desloratadine in patients with a history of convulsions, especially in pediatric patients.

If convulsions develop, the use of desloratadine should be discontinued.

Effect on ability to drive vehicles and operate machinery

The potential for the development of such side effects as dizziness and drowsiness should be taken into account.

If the described adverse events occur, one should refrain from performing these activities.

Overdose

Symptoms: taking a dose 5 times higher than the recommended one does not lead to any symptoms.

In clinical studies, daily use of desloratadine in adults and adolescents at doses up to 20 mg for 14 days was not accompanied by statistically or clinically significant changes in the cardiovascular system.

In a clinical and pharmacological study, the use of desloratadine at a dose of 45 mg/day (9 times higher than the recommended one) for 10 days did not cause QT interval prolongation and was not accompanied by the occurrence of serious side effects.

Treatment: in case of accidental ingestion of a large amount of the drug, it is necessary to consult a doctor immediately.

Gastric lavage, intake of activated charcoal is recommended; if necessary – symptomatic therapy.

Desloratadine is not removed by hemodialysis; the effectiveness of peritoneal dialysis has not been established.

Drug Interactions

When studying drug interactions with repeated concomitant use of desloratadine with ketoconazole, erythromycin, azithromycin, fluoxetine and cimetidine, no clinically significant changes in the plasma concentration of desloratadine were detected.

Concomitant intake of food or consumption of grapefruit juice does not affect the effectiveness of the drug.

Lordestin^® syrup 0.5 mg/ml does not enhance the effect of alcohol on the central nervous system.

Nevertheless, during post-registration use, cases of alcohol intolerance and alcohol intoxication have been recorded.

Therefore, Desloratadine should be used with caution simultaneously with alcohol.

Storage Conditions

The drug should be stored out of the reach of children, protected from light, at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 2 years. Do not use after the expiration date printed on the package.

Dispensing Status

The drug is available without a prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.