Loratadine

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT LO RATADINE (Loratadine)

Composition:

Active substance: loratadine;

1 tablet contains 10 mg of loratadine (0.01 g);

Excipients: lactose monohydrate, corn starch, magnesium stearate, colloidal anhydrous silicon dioxide, microcrystalline cellulose.

Pharmaceutical form. Tablets.

Main physicochemical properties: white or almost white tablets with a score line and bevel.

Pharmacotherapeutic group. Antihistamines for systemic use.

ATC code R06A X13.

Pharmacological properties.

Pharmacodynamics.

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

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

Skin challenge tests with histamine following a single 10 mg dose showed that the antihistaminic 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.

Pharmacokinetics.

Absorption. Loratadine is rapidly and well absorbed. Administration with food may slightly delay loratadine absorption, but this 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 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 main metabolite, desloratadine, is pharmacologically active and largely responsible for the clinical effect. Loratadine and desloratadine reach maximum plasma concentrations (Tmax) at 1–1.5 hours and 1.5–3.7 hours, respectively, after drug administration.

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

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 twice as high, while levels of 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 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 drug are not enhanced, as confirmed by psychomotor function studies.

Potential interaction may occur when co-administered with known inhibitors of CYP3A4 or CYP2D6, leading to increased levels of loratadine, which in turn may increase the frequency of adverse reactions.

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 drugs have been conducted only in adult patients.

Special precautions for use.

Loratadine should be used with caution in patients with severe impairment of liver function.

The drug contains lactose. For this reason, patients with such rare hereditary diseases as galactose intolerance, Lapp lactase deficiency, and glucose-galactose malabsorption should not take this drug.

The drug should be discontinued at least 48 hours before skin testing, since antihistamines can neutralize or otherwise reduce the positive reaction when determining skin reactivity index.

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 abnormalities and is non-toxic to the fetus and newborn. Animal studies have not revealed any direct or indirect adverse effects related to reproductive toxicity. As a precautionary measure, it is advisable to avoid using the drug during pregnancy.

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

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

Ability to influence reaction speed when driving or operating machinery.

In clinical studies assessing the ability to drive a vehicle, no changes were observed in patients taking loratadine. Loratadine 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.

Dosage and Administration

Administration

Oral use. Tablets may be taken regardless of food intake.

Dosage

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

For children aged 2 to 12 years, dosage depends on body weight.

Body weight above 30 kg: 10 mg (1 tablet) once daily. For children with body weight below 30 kg, the syrup formulation should be used.

Elderly patients

Dosage adjustment is not required for elderly patients.

Patients with hepatic impairment

In patients with severe hepatic impairment, a lower initial dose should be administered due to potentially reduced loratadine clearance. For adults and children with body weight above 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.

Loratadine tablets should be administered to children with body weight above 30 kg.

Overdose

Overdose of loratadine increases the frequency of anticholinergic symptoms. In cases of overdose, somnolence, tachycardia, and headache have been reported. 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 effectively removed by hemodialysis; the efficacy 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. When loratadine was used 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 more common adverse reactions reported more frequently than with placebo were: somnolence (1.2%), headache (0.6%), increased appetite (0.5%), and insomnia (0.1%). In children aged 2 to 12 years, the following adverse events were observed: headache (2.7%), nervousness (2.3%), and fatigue (1.0%).

List of adverse reactions. Adverse reactions reported during the post-marketing period are listed below by system organ classes. Frequency is defined as follows: 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.

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

Nervous system disorders: very rare – dizziness, convulsions.

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: not known – weight gain.

Shelf life.

3 years.

Storage conditions.

Keep out of reach of children. Store in the original packaging at a temperature not exceeding 25 °C.

Packaging.

10 tablets per blister pack, 1, 2, 50, or 100 blister packs per carton.

Prescription status.

Over-the-counter – pack sizes № 10, № 20. For hospital use – pack sizes № 500, № 1000.

Manufacturer.

Private Joint-Stock Company "Lekhim-Kharkiv". PJSC "Tekhnolog".

Manufacturer's address and location of operations.

Ukraine, 61115, Kharkiv region, city of Kharkiv, Severina Pototskogo Street, 36.

Ukraine, 20300, Cherkasy region, city of Uman, Stara Prorina Street, 8.