Loratadine-darnitsa

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT LORATADINE-DARNITSA (LORATADINE-DARNITSA)

Composition:

Active substance: loratadine;

1 tablet contains loratadine 10 mg;

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

Pharmaceutical form. Tablets.

Main physicochemical properties: round, flat-surfaced tablets, white or white with a yellowish tinge, with a score line and a groove.

Pharmacotherapeutic group. Antihistamines for systemic use. Loratadine. ATC code R06A X13.

Pharmacological Properties

Pharmacodynamics

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

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

Skin tests for histamine reactivity 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 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 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 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 treating chronic idiopathic urticaria, as demonstrated by reduction in itching, erythema, and allergic rash. In these studies, the incidence of somnolence was similar with loratadine and placebo.

Children. Efficacy in children was similar to that in adults.

Pharmacokinetics

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

Distribution. Loratadine is highly bound (97–99%) to plasma proteins, while its active metabolite is moderately bound (73–76%).

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 liver metabolism, primarily via CYP3A4 and CYP2D6. The main metabolite, desloratadine, is pharmacologically active and largely responsible for the clinical effect. Loratadine and desloratadine reach maximum plasma concentrations (Cmax) at 1–1.5 hours and 1.5–3.7 hours, respectively, after drug 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—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 Cmax values of loratadine and its active metabolite were increased compared to those in 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 values of loratadine were twice as high, while those of its 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.

Hypersensitivity to the active substance or to any of the excipients of the medicinal product.

Interaction with other medicinal products and other forms of interaction.

Effects of loratadine are not enhanced when used concomitantly with alcohol, 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.

Controlled studies have reported increased plasma concentrations of loratadine 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 medicinal product should be used with caution in patients with severe hepatic impairment.

The medicinal product must be discontinued at least 48 hours prior to skin testing, as antihistamines may neutralize or otherwise reduce a positive reaction when determining skin reactivity index.

The medicinal product contains lactose; therefore, tablets Loratadine-Darnitsia should not be administered to patients with rare hereditary forms of galactose intolerance, lactase deficiency, or glucose-galactose malabsorption syndrome.

This medicinal product contains sodium. This should be taken into account in patients on a sodium-controlled diet.

Use during pregnancy or breastfeeding

Pregnancy. There is very limited data on the use of loratadine in pregnant women. Animal studies have not revealed direct or indirect adverse effects related to reproductive toxicity. For safety reasons, it is advisable to avoid using this medicinal product during pregnancy.

Breastfeeding period. Physicochemical data indicate excretion of loratadine and its metabolites into breast milk. Since the risk to the infant cannot be excluded, the medicinal product should not be used during breastfeeding.

Fertility. There are no data available on the effect of the medicinal product on male or female fertility.

Ability to influence reaction speed when driving or operating machinery

The medicinal product has no effect or only a negligible effect on the ability to drive or operate machinery.

However, patients should be informed about the very rare occurrence of drowsiness. In such cases, the ability to drive or operate machinery may be impaired.

Dosage and Administration.

Adults and children aged 12 years and older.

The medicinal product should be administered at a dose of 10 mg once daily.

Children aged 2 to 12 years with body weight above 30 kg.

The medicinal product should be administered at a dose of 10 mg once daily.

Children aged 2 to 12 years with body weight below 30 kg.

Loratadine preparations should be used in another pharmaceutical form.

Elderly patients and patients with renal impairment.

There is no need for dose adjustment.

Patients with hepatic impairment.

In patients with severe hepatic impairment, dose adjustment is required due to possible reduction in loratadine clearance (recommended initial dose: 10 mg every other day).

Treatment duration.

The duration of treatment should be determined by a physician based on the course of the disease.

Food intake does not affect the action of the medicinal product.

Children.

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

The medicinal product can be administered to children aged 2 years and older with body weight above 30 kg.

Overdose.

Loratadine overdose increases the frequency of anticholinergic symptoms.

Symptoms: drowsiness, tachycardia, headache.

Treatment: gastric lavage, administration of activated charcoal, symptomatic and supportive therapy.

Loratadine is not removed by hemodialysis; it is also unknown whether loratadine is removed by peritoneal dialysis.

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 reported in 2% of patients (exceeding the rate in patients receiving placebo) when loratadine was administered at the recommended dose of 10 mg once daily for indications including allergic rhinitis and chronic idiopathic urticaria. The most commonly reported adverse reactions, occurring more frequently than with placebo, 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 observed: headache (2.7%), nervousness (2.3%), or fatigue (1%).

List of adverse reactions. Adverse reactions reported during the post-marketing period are listed below by system organ classes. 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.

Gastrointestinal disorders: very rare – nausea, vomiting, dry mouth, gastritis, increased appetite; frequency not known – weight gain.

Hepatobiliary disorders: very rare – liver function abnormalities.

Nervous system disorders: very rare – dizziness, somnolence, headache, insomnia, convulsions.

Cardiac disorders: very rare – tachycardia, palpitations.

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

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

General disorders: very rare – fatigue.

In children aged 2 to 12 years, headache, nervousness, and fatigue were observed.

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after a medicinal product is authorized is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are required to report any suspected adverse reactions via the national reporting system.

Shelf life. 3 years.

Storage conditions.

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

Keep out of reach and sight of children.

Packaging.

10 tablets in a blister pack; 1 blister pack in a carton.

Prescription status. Over-the-counter

Manufacturer. JSC "Pharmaceutical Company "Darnytsia".

Manufacturer's address and location of its business activities.

13, Boryspylska Street, Kyiv, 02093, Ukraine.