Lorizan

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT LORIZANâ (LORIZAN)

Composition:

Active substance: loratadine;

1 tablet contains loratadine 10 mg;

Excipients: lactose monohydrate; potato starch; calcium stearate.

Pharmaceutical form. Tablets.

Main physicochemical properties: white tablets with a flat surface, bevelled edge.

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 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 receptors. The drug does not inhibit norepinephrine uptake and has virtually no effect on cardiovascular system function or cardiac pacemaker activity.

Skin challenge tests with histamine 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 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 superior to placebo in treating chronic idiopathic urticaria, as demonstrated by reduction in itching, erythema, and hives. 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 extensively 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% 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 extensively absorbed and undergoes extensive first-pass metabolism in the liver, primarily via CYP3A4 and CYP2D6. The major metabolite, desloratadine, is pharmacologically active and largely responsible for the clinical effect. Loratadine and desloratadine reach peak plasma concentrations (Tmax) 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 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 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 renal 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 approximately 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.

Lorizan® 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.

Effects of the drug are not enhanced when used concomitantly with alcohol, as confirmed by psychomotor function studies.

Potential interactions may occur when using known inhibitors of CYP3A4 or CYP2D6, which may lead to increased levels of loratadine, possibly resulting in a higher incidence of adverse reactions.

Increased plasma concentrations of loratadine have been reported following concomitant administration with ketoconazole, erythromycin, and cimetidine; however, these increases were not associated with clinically significant changes (including on ECG).

Children. Interaction studies with other medicinal products have been conducted only in adult patients.

Special precautions for use.

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

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

Treatment with Lorizan® should be discontinued at least 48 hours before skin testing, as antihistamines may neutralize or otherwise reduce the positive reaction in 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. However, as a precautionary measure, it is advisable to avoid using loratadine during pregnancy.

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

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

Ability to influence reaction rate when driving or operating machinery.

In clinical studies assessing the ability to drive, 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 warned that somnolence has been very rarely reported, which may affect the ability to drive a vehicle or operate machinery.

Dosage and Administration

Route of Administration

Oral use. 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. If body weight is more than 30 kg: 10 mg (1 tablet) once daily. For children with body weight less than 30 kg, the syrup formulation should be used.

Elderly patients

Dosage adjustment is not required for elderly individuals.

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. The tablet formulation should be administered only to children with body weight over 30 kg.

Overdose

Overdose of loratadine increases the frequency of anticholinergic symptoms. Symptoms reported with overdose include somnolence, tachycardia, and headache. 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 effectively removed by hemodialysis; the efficacy of peritoneal dialysis in removing the drug is unknown. After emergency treatment, the patient should remain under medical supervision.

Adverse Reactions.

Brief overview 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 common adverse reactions more frequent than in 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 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 – 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 – pathological changes in liver function.

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

General disorders: rare – fatigue.

Investigations: not known – weight gain.

Shelf life. 3 years.

Storage conditions.

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

Packaging.

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

Prescription status. Over-the-counter.

Manufacturer. JSC "Kyivmedpreparat".

Manufacturer's address and location of business activity.

139 Saksaganskogo Street, Kyiv, 01032, Ukraine.

Date of last review.