Loratadine-stoma

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT LO RATADINE-STOMA

Composition:

Active substance: loratadine;

1 tablet contains loratadine calculated to 100 % substance (0.01 g) 10 mg;

Excipients: lactose monohydrate, potato starch, magnesium stearate.

Pharmaceutical form. Tablets.

Main physicochemical properties: white tablets with flat surface, scored line and chamfer.

Pharmacotherapeutic group. Antihistamines for systemic use.

ATC code R06AX13.

Pharmacological Properties

Pharmacodynamics

Loratadine is a tricyclic antihistamine with selective activity on peripheral H₁-histamine receptors.

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

Skin tests with histamine challenge after a single 10 mg dose showed that the antihistaminic effect begins within 1–3 hours, reaches its peak at 8–12 hours, and lasts more than 24 hours. No development of tolerance to loratadine was observed after 28 days of treatment.

Clinical Efficacy and Safety

More than 10,000 individuals (aged 12 years and older) received loratadine (10 mg tablets) in controlled clinical trials. Loratadine (10 mg tablets) administered once daily was more effective than placebo and as 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 a frequency similar to that 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 the treatment of chronic idiopathic urticaria, as demonstrated by reduction in pruritus, erythema, and allergic rash. In these studies, the incidence of somnolence was similar between loratadine and placebo.

Children

Approximately 200 children (aged 6 to 12 years) with seasonal allergic rhinitis received loratadine at doses up to 10 mg once daily in controlled clinical trials. In another study, 60 children (aged 2 to 5 years) received loratadine 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 extensively absorbed. Administration with food may slightly delay absorption, but does not affect the clinical effect. The 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 distribution 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 undergoes extensive first-pass metabolism in the liver, primarily via CYP3A4 and CYP2D6. The primary metabolite, desloratadine, is pharmacologically active and largely responsible for the clinical effect. Loratadine and desloratadine reach peak plasma concentrations (T_max) 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 over 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—either as loratadine or desloratadine.

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

Renal Impairment

In patients with chronic renal impairment, AUC and maximum plasma concentration (C_max) 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 that 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 C_max of loratadine were approximately twice as high, while the 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.

Loratadine-Stoma 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 Loratadine-Stoma are not enhanced, as confirmed by psychomotor function studies.

A potential interaction may occur when using known inhibitors of CYP3A4 or CYP2D6, resulting in increased loratadine levels, which in turn may lead to an increased incidence 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

Loratadine-Stoma should be used with caution in patients with severe hepatic impairment.

The product contains lactose. For this reason, patients with rare hereditary conditions such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medication.

Treatment with Loratadine-Stoma should be discontinued at least 48 hours before skin testing, as antihistamines may neutralize or otherwise reduce the positive reaction in skin sensitivity tests.

Use during pregnancy or breastfeeding

Pregnancy

A substantial amount of data on use during pregnancy (over 1000 outcomes) indicates that loratadine does not cause developmental malformations and is not toxic to the fetus or 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 Loratadine-Stoma during pregnancy.

Breastfeeding

Physicochemical data indicate that loratadine and its metabolites are excreted into breast milk. Since a risk to the infant cannot be excluded, Loratadine-Stoma should not be used during breastfeeding.

Fertility

There are no data available on the effect of the drug on female or male fertility.

Ability to influence reaction speed when driving or operating machinery

Clinical studies assessing the ability to drive have shown no changes in patients treated with loratadine. Loratadine-Stoma has no effect or only a negligible effect on the ability to drive or operate machinery. However, patients should be informed that somnolence has very rarely been reported, which may affect the ability to drive or operate machinery.

Dosage and Administration.

Route of Administration

Oral use. Tablets may 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.

The dose for children aged 2 to 12 years depends on body weight. For body weight over 30 kg: 10 mg (1 tablet) once daily. Children with body weight less than 30 kg should receive the drug in syrup form.

Elderly patients

Dosage adjustment is not required for elderly patients.

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 the drug in children under 2 years of age have not been established.

Loratadine-Stoma tablets should be prescribed to children with body weight over 30 kg.

Overdose

Overdose of loratadine increases the frequency of occurrence of anticholinergic symptoms. In cases of overdose, somnolence, tachycardia, and headache have been reported. In case 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.

Short description of the safety profile.

In clinical studies involving adults and adolescents, adverse reactions were observed in 2% of patients receiving loratadine at the recommended dose of 10 mg once daily for indications including allergic rhinitis and chronic idiopathic urticaria (exceeding the rate in placebo-treated patients). The most common adverse reactions more frequently reported compared to the placebo group were: somnolence (1.2%), headache (0.6%), increased appetite (0.5%), and insomnia (0.1%). In clinical studies in children aged 2 to 12 years, the following adverse events were reported: 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 is 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 frequency not known (cannot be estimated from available data).

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

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

Nervous system disorders: very rare — dizziness, seizures.

Cardiac disorders: very rare — tachycardia, palpitations.

Gastrointestinal disorders: very rare — nausea, dry mouth, gastritis.

Hepatobiliary disorders: very rare — pathological changes in liver function.

Skin and subcutaneous tissue disorders: very rare — rash, alopecia.

General disorders and administration site conditions: very rare — fatigue.

Investigations: frequency not known — weight increase.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after drug registration is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy via the Automated Information System for Pharmacovigilance at the following link: https://aisf.dec.gov.ua

Shelf life. 4 years.

Storage conditions.

Keep out of reach and sight of children.

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

Packaging.

10 tablets in a blister pack, 1 blister pack per carton; 20 tablets in a polymer bottle, 1 bottle per carton.

Prescription status. Over-the-counter.

Manufacturer. JSC "STOMA".

Manufacturer's name and address of the place of business. 3, Newtona Street, Kharkiv, Ukraine, 61105.