Loratadine-zdorovya

INSTRUCTIONS FOR MEDICAL USE|consumption| OF THE MEDICINAL PRODUCT LORATADINE-ZDOROVYE (LORATADINE-ZDOROVYE)

Composition:

Active substance: loratadine;

1 tablet contains 10 mg of loratadine;

Excipients: lactose monohydrate, maize starch, colloidal anhydrous silicon dioxide, povidone, magnesium stearate, sodium croscarmellose.

Pharmaceutical form. Tablets.

Main physicochemical properties: white or white with a yellowish tint, flat cylindrical shaped tablets with a score line.

Pharmacotherapeutic group. Antihistamines for systemic use.

ATC code R06AX13.

Pharmacological properties.

Pharmacodynamics.

Loratadine (the active substance of the medicinal product) is a tricyclic antihistamine with selective activity towards peripheral H1-receptors.

In most patients, at the recommended dose, loratadine does not produce clinically significant sedative or anticholinergic effects. During prolonged treatment, no clinically significant changes in vital functions, laboratory test results, physical examination findings, or electrocardiograms were observed. Loratadine has no significant effect on H2-histamine receptors. The drug does not inhibit norepinephrine uptake and has virtually no effect on cardiovascular system function or cardiac pacemaker activity.

Skin tests for histamine conducted after a single 10 mg dose demonstrated that the antihistamine effect begins within 1–3 hours, reaches its peak within 8–12 hours, and lasts for more than 24 hours. No development of tolerance to the drug's effect was observed after 28 days of loratadine administration.

Clinical efficacy and safety.

More than 10,000 individuals (aged 12 years and older) received loratadine treatment (10 mg tablets) in controlled clinical trials. Loratadine (tablets) at a dose of 10 mg once daily was more effective than placebo and equally effective as clemastine in improving symptoms (nasal and non-nasal) of allergic rhinitis. In these studies, somnolence occurred less frequently with loratadine than with clemastine and occurred at approximately the same frequency as with terfenadine and placebo.

Among participants in these studies (aged 12 years and older), 1,000 patients with chronic idiopathic urticaria were enrolled in placebo-controlled trials. Loratadine at a dose of 10 mg once daily was more effective than placebo in treating chronic idiopathic urticaria, as evidenced by reduction in itching, erythema, and allergic rash. In these studies, the frequency of somnolence was similar with loratadine and placebo.

Children.

Approximately 200 children (aged 6 to 12 years) with seasonal allergic rhinitis received loratadine (syrup) at doses up to 10 mg once daily in controlled clinical trials. In another study, 60 children (aged 2 to 5 years) received loratadine (syrup) at a dose of 5 mg once daily. No unexpected adverse reactions were observed.

Efficacy in children was similar to that in adults.

Pharmacokinetics.

Absorption. Loratadine is rapidly and well absorbed. Administration with food may slightly delay loratadine absorption, but this does not affect the clinical effect. Bioavailability parameters of loratadine and its active metabolite are dose-proportional.

Distribution. Loratadine is highly bound (97% to 99%) to plasma proteins, while its active metabolite is moderately bound (73% to 76%). In healthy volunteers, the plasma half-life of loratadine and its active metabolite is approximately 1 hour and 2 hours, respectively.

Biotransformation. After oral administration, loratadine is rapidly and well absorbed and extensively metabolized during first-pass metabolism in the liver, primarily via CYP3A4 and CYP2D6. The main metabolite, desloratadine, is pharmacologically active and largely responsible for the clinical effect. Loratadine and desloratadine reach peak plasma concentrations (Tmax) at 1–1.5 hours and 1.5–3.7 hours, respectively, after administration.

Elimination. Approximately 40% of the dose is excreted in urine and 42% in feces within 10 days, primarily as conjugated metabolites. About 27% of the dose is excreted in urine within the first 24 hours. Less than 1% of the active substance is excreted unchanged in active form as loratadine or desloratadine.

In healthy adult volunteers, the mean elimination half-life of loratadine is 8.4 hours (range: 3 to 20 hours), and that of the main active metabolite is 28 hours (range: 8.8 to 92 hours).

Renal impairment. In patients with chronic renal impairment, AUC and maximum plasma concentration (Cmax) of loratadine and its active metabolite were increased compared to patients with normal renal function. The mean elimination half-life of loratadine and its active metabolite did not differ significantly from values in healthy volunteers. In patients with chronic hepatic impairment, hemodialysis does not affect the pharmacokinetics of loratadine and its active metabolite.

Hepatic impairment. In patients with chronic alcoholic liver disease, AUC and Cmax of loratadine were approximately twice as high, while corresponding values for the active metabolite did not change significantly compared to patients with normal liver function. The elimination half-life of loratadine and its active metabolite is 24 and 37 hours, respectively, and increases depending on the severity of liver disease.

Elderly patients. Pharmacokinetic parameters of loratadine and its active metabolite were similar in healthy adult volunteers and healthy elderly volunteers.

Clinical characteristics.

Indications.

Symptomatic treatment of allergic rhinitis and chronic idiopathic urticaria.

Contraindications.

The medicinal product is contraindicated in patients with hypersensitivity to the active substance or to any other component of the medicinal product.

Interaction with other medicinal products and other forms of interaction.

When used concomitantly with alcohol, the effects of the medicinal product are not enhanced, as confirmed by psychomotor function studies.

Potential interaction may occur when using known inhibitors of CYP3A4 or CYP2D6, leading to increased levels of loratadine, which in turn may cause an increased frequency of adverse reactions.

In controlled studies, increased plasma concentrations of loratadine have been reported after concomitant administration with ketoconazole, erythromycin, and cimetidine, without clinically significant changes (including on ECG).

Children. Interaction studies with other medicinal products have been conducted only in adult patients.

Special precautions for use.

The drug should be used with caution in patients with severe hepatic impairment.

Administration of the drug must be discontinued at least 48 hours prior to skin testing, since antihistamines may suppress or otherwise diminish the positive reaction in skin reactivity tests.

The drug contains lactose; therefore, if the patient has known intolerance to certain sugars, consultation with a physician is necessary before taking this medicinal product.

Use during pregnancy or breastfeeding.

Pregnancy.

Extensive data from use during pregnancy (over 1000 outcomes) indicate that loratadine does not cause developmental malformations and is non-toxic to the fetus and newborn. Animal studies have not revealed any direct or indirect adverse effects related to reproductive toxicity. However, as a precautionary measure, it is advisable to avoid using the drug during pregnancy.

Breastfeeding period. Physicochemical data indicate excretion of loratadine/metabolites into breast milk. Since a risk to the infant cannot be excluded, the drug should not be used during breastfeeding.

Fertility. There are no data available regarding the effect of loratadine on male or female fertility.

Ability to influence reaction rate while driving or operating machinery.

Clinical studies assessing the ability to drive showed no changes in patients treated with loratadine. The drug has no effect or only a negligible effect on the ability to drive a vehicle or operate machinery. However, patients should be informed that very rare cases of somnolence have been reported, which may affect the ability to drive a vehicle or operate machinery.

Method of Administration and Dosage.

Method of Administration. Orally. Tablets can be taken regardless of food intake.

Dosage. Adults and children aged 12 years and older should take 1 tablet (10 mg of loratadine) once daily.

For children aged 2 to 12 years, dosage depends on body weight. For body weight over 30 kg: 10 mg (1 tablet) once daily. For children with body weight less than 30 kg, the syrup formulation should be used.

Elderly patients. Dosage adjustment is not required for elderly individuals.

Patients with hepatic impairment. Patients with severe hepatic impairment should receive a lower initial dose, as loratadine clearance may be reduced. For adults and children with body weight over 30 kg, the recommended initial dose is 10 mg every other day.

Patients with renal impairment. Dosage adjustment is not necessary for patients with renal impairment.

Children.

The efficacy and safety of loratadine in children under 2 years of age have not been established.

The tablet formulation should be administered to children with body weight over 30 kg.

Overdose.

Loratadine overdose increases the frequency of occurrence of anticholinergic symptoms. In cases of overdose, somnolence, tachycardia, and headache have been reported. In the event of overdose, symptomatic and supportive treatment is recommended for the required duration. Administration of activated charcoal as an aqueous suspension may be considered. Gastric lavage may also be performed. Loratadine is not removed from the body by hemodialysis; the effectiveness of peritoneal dialysis in eliminating the drug is unknown. After emergency treatment, the patient should remain under medical supervision.

Adverse Reactions

Summary of safety profile. In clinical trials involving adults and adolescents receiving loratadine at the recommended dose of 10 mg once daily for indications including allergic rhinitis and chronic idiopathic urticaria, adverse reactions were reported in 2% of patients (exceeding the rate in patients receiving placebo). The most common adverse reactions compared to placebo group were: somnolence (1.2%), headache (0.6%), increased appetite (0.5%), and insomnia (0.1%). In clinical trials in children aged 2 to 12 years, the following adverse events were observed: headache (2.7%), nervousness (2.3%), and fatigue (1%).

List of adverse reactions. Adverse reactions reported during the post-marketing period are listed below by system organ class. Frequency categories are defined as: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), and not known (cannot be estimated from available data).

Within each frequency group, adverse reactions are listed in order of decreasing severity.

Nervous system disorders: rare – dizziness, convulsions.

Cardiac disorders: rare – palpitations, tachycardia.

Gastrointestinal disorders: rare – dry mouth, nausea, gastritis.

Hepatobiliary disorders: rare – hepatic function abnormalities.

Skin and subcutaneous tissue disorders: rare – rash, alopecia.

Immune system disorders: rare – hypersensitivity reactions, including anaphylaxis and angioedema.

General disorders: rare – fatigue.

Investigations: not known – weight gain.

Shelf life. 4 years.

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

Keep out of reach and sight of children.

Packaging. Tablets, pack sizes: №10, №10×2 in blisters in a box.

Supply category. Over-the-counter.

Manufacturer. LIMITED LIABILITY COMPANY "CORPORATION "ZDOROVYA".

Manufacturer's address and place of business. 22, Shevchenka Street, Kharkiv, 61013, Kharkiv region, Ukraine.