Loratadine

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT LORATADINE

Composition:

Active substance: loratadine;

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

Excipients: potato starch, lactose monohydrate, povidone, calcium stearate.

Pharmaceutical form. Tablets.

Main physicochemical properties: white, round-shaped tablets with a flat surface, with bevel and score line or without score line.

Pharmacotherapeutic group. Antihistamines for systemic use.

ATC Code R06A X13.

Pharmacological Properties.

Pharmacodynamics.

Loratadine is a tricyclic antihistamine with selective activity toward 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 were observed in vital function parameters, laboratory tests, physical examination, or electrocardiograms. Loratadine has no significant effect on H2-histamine receptors. The drug does not inhibit norepinephrine uptake and essentially has no effect on cardiovascular system function or cardiac pacemaker activity.

Skin tests with histamine after a single 10 mg dose showed that the antihistamine effect begins within 1–3 hours, reaches its peak within 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 patients (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 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 demonstrated by reduction in itching, erythema, and allergic rash. In these studies, the incidence 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 absorption of loratadine, 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 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 concentration (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 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 of the main active metabolite, 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 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 individuals. 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 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 chronic idiopathic urticaria and allergic rhinitis.

Contraindications.

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

Interaction with other medicinal products and other forms of interaction.

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

A potential interaction may occur when using known inhibitors of CYP3A4 or CYP2D6, leading to increased loratadine levels, which in turn may cause an increased 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. If you have been diagnosed with an intolerance to certain sugars, consult your doctor before taking this medication. Patients with such rare hereditary diseases as galactose intolerance, lactase deficiency, or glucose-galactose malabsorption should not take this drug.

Treatment with loratadine must be discontinued at least 48 hours prior to skin testing, since antihistamines can neutralize or otherwise reduce the positive reaction when determining skin reactivity index.

Use during pregnancy or breast-feeding.

Pregnancy. A substantial amount of data from 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. However, as a precautionary measure, it is advisable to avoid using loratadine during pregnancy.

Breast-feeding. Physicochemical data indicate excretion of loratadine and its metabolites into breast milk. Since the risk to the infant cannot be excluded, loratadine should not be used during breast-feeding.

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

Ability to influence the reaction rate when driving or operating machinery.

In clinical studies assessing the ability to drive, no changes were observed in patients taking 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 warned 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

Orally. Tablets can be taken regardless of food intake.

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. Children with body weight above 30 kg: 10 mg (1 tablet) once daily. Children with body weight below 30 kg should receive loratadine in the form of syrup.

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 above 30 kg, the recommended initial dose is 10 mg every other day.

Patients with renal impairment. No dosage adjustment is 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 prescribed only 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. 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.

Short description of the 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 more common adverse reactions compared to the 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%), 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 not known (cannot be estimated from available data).

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

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

Nervous system disorders: rare – dizziness, convulsions.

Cardiac disorders: rare – tachycardia, palpitations.

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

Hepatobiliary disorders: rare – liver function abnormalities.

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

General disorders: rare – fatigue.

Investigations: not known – weight gain.

Shelf life. 4 years.

Do not use the medicinal product after the expiry date stated on the packaging.

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

Keep out of reach of children.

Packaging. 10 tablets in a blister. 1 or 2 blisters per carton.

Pharmaceutical classification. Over-the-counter (without prescription).

Manufacturer. JSC "Farmak".

Manufacturer's name and address of the place of business.

74, Kyrylivska Street, Kyiv, 04080, Ukraine.