Claritin

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT KLA RITINâ (CLARITINEâ)

Composition:

Active substance: loratadine;

1 tablet contains loratadine 10 mg;

Excipients: lactose monohydrate, corn starch, magnesium stearate.

Pharmaceutical form. Tablets.

Main physicochemical properties: oval tablets, white or almost white, with a break line on one side and a flat surface on the other side, free from foreign inclusions.

Pharmacotherapeutic group. Antihistamines for systemic use.

ATC code R06A X13.

Pharmacological Properties.

Pharmacodynamics.

Loratadine (the active ingredient of Claritin®) is a tricyclic antihistamine with selective activity against peripheral H1-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 in vital function parameters, 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 function or cardiac pacemaker activity.

Studies involving histamine skin testing after a single 10 mg dose showed that the antihistaminic effect begins within 1–3 hours, reaches its peak within 8–12 hours, and lasts more than 24 hours. There was no evidence of developing tolerance to the drug's effect 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 occurred at a frequency similar to that with terfenadine and placebo.

Among participants in these trials (aged 12 years and older), 1,000 patients with chronic idiopathic urticaria were enrolled in placebo-controlled studies. 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 through 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 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 over 10 days, primarily as conjugated metabolites. Approximately 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 primary active metabolite was 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 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 corresponding values for the active metabolite did not change significantly compared to those in 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.

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

Clinical characteristics.

Indications.

Symptomatic treatment of allergic rhinitis and chronic idiopathic urticaria.

Contraindications.

Claritin® 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 Claritin® are not enhanced, as confirmed by psychomotor function studies.

Potential interaction may occur when using known inhibitors of CYP3A4 or CYP2D6, resulting in increased levels of loratadine, 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.

Claritin® should be used with caution in patients with severe hepatic impairment.

The product contains lactose. Patients with established sugar intolerances and rare hereditary problems such as galactose intolerance, lactase deficiency, or glucose-galactose malabsorption should not take this medicine.

Treatment with Claritin® must be discontinued at least 48 hours before skin testing, since antihistamines may suppress or otherwise diminish positive skin reactivity responses.

Use during pregnancy or breastfeeding.

Pregnancy. Extensive data from use during pregnancy (over 1000 outcomes) indicate that loratadine is not associated with congenital 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 Claritin® during pregnancy.

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

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

Effect on ability to drive and use machines.

Clinical studies assessing the ability to drive have shown no changes in patients taking loratadine. Claritin® has no effect or negligible effect on the ability to drive or operate machinery. However, patients should be warned that somnolence has been reported very rarely and may affect the ability to drive or operate machinery.

Dosage and Administration.

Administration method.

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. Children weighing more than 30 kg should receive 10 mg (1 tablet) once daily. Children weighing less than 30 kg should be administered the syrup formulation.

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

Claritin® tablets should be prescribed only to children with body weight over 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, 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 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%), and 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 cases – hypersensitivity reactions, including anaphylaxis and angioedema.

Nervous system disorders: rare cases – dizziness, seizures.

Cardiac disorders: rare cases – tachycardia, palpitations.

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

Hepatobiliary disorders: rare cases – pathological changes in liver function.

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

General disorders: rare cases – fatigue.

Investigations: frequency not known – weight gain.

Shelf life. 3 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C in a place inaccessible to children.

Packaging.

7 or 10 tablets in a blister pack, 1 blister pack in a cardboard box.

Supply category. Over-the-counter.

Manufacturer.

Bayer Bitterfeld GmbH.

Manufacturer's address.

Ortsteil Gräbendorf, Seeliger Straße 1, 06803 Bitterfeld-Wolfen, Germany.