Loratadine

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT LORATADINE

Composition:

Active substance: loratadine;

1 tablet contains 10 mg of loratadine;

Excipients: lactose monohydrate; potato starch; calcium stearate.

Pharmaceutical form. Tablets.

Main physicochemical characteristics: white or almost white, round, flat-surfaced tablets with beveled edges.

Pharmacotherapeutic group. Systemic antihistamines.

ATC code R06A X13.

Pharmacological Properties

Pharmacodynamics

Loratadine is a tricyclic selective blocker of peripheral H1-histamine receptors. When administered at the recommended dose, it does not produce clinically significant sedative or anticholinergic effects. During prolonged treatment, no clinically significant changes have been observed in vital function parameters, laboratory test results, physical examination findings, or electrocardiograms. Loratadine does not significantly affect H2-histamine receptor activity. It does not block norepinephrine uptake and has virtually no effect on the cardiovascular system or pacemaker activity.

Skin testing for histamine response after a single 10 mg dose demonstrated 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 treatment.

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 observed 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 evidenced by reduction in itching, erythema, and allergic rash. In these trials, 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 observed 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. 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 elimination 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 enzymes. 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 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 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 maximum plasma concentration (Cmax) of loratadine and its active metabolite were increased compared to those 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 were not significantly altered 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.

Effects of the drug 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 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; however, these changes were not associated with clinically significant effects (including on ECG).

Children. Interaction studies with other medicinal products 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, this medication should not be administered to patients with rare hereditary conditions such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.

Loratadine therapy should be discontinued at least 48 hours prior to skin testing, as antihistamines may neutralize or otherwise reduce the positive reaction when determining skin reactivity index.

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. As a precautionary measure, it is advisable to avoid using loratadine during pregnancy.

Breastfeeding. Data are available indicating that loratadine and/or its metabolites are excreted into breast milk. Since the risk to the infant cannot be excluded, loratadine should not be used during breastfeeding.

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

Ability to influence reaction rate when driving or operating machinery.

Loratadine has no effect or only a negligible effect on the ability to drive or operate machinery. However, patients should be informed that somnolence has been reported very rarely, which may affect the ability to drive or operate machinery.

Method of Administration and Dosage

Method of Administration

Oral use. Tablets may 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. For 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 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 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 the drug in children under 2 years of age have not been established.

The tablet formulation should be administered only when body weight exceeds 30 kg.

Overdose

Overdose of loratadine increases the frequency of anticholinergic symptoms. Symptoms reported in cases of 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 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 studies involving adults and adolescents, adverse reactions were reported in 2% of patients receiving loratadine at the recommended dose of 10 mg once daily for indications including allergic rhinitis and chronic idiopathic urticaria. The most commonly reported adverse reactions 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 increased fatigue (1%).

List of adverse reactions. Adverse reactions reported during the post-marketing period are listed below by system organ class. 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: very rare – anaphylaxis, including 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 – increased fatigue.

Shelf life. 5 years.

Storage conditions.

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

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 operations.

139 Saksaganskogo Street, Kyiv, 01032, Ukraine.

INSTRUCTION

for medical use of medicinal product

LORATADINE

(LORATADINE)

Composition:

Active ingredient: loratadine;

1 tablet contains loratadine 10 mg;

Excipients: lactose monohydrate; potato starch; calcium stearate.

Pharmaceutical form. Tablets.

Main physicochemical characteristics: white or almost white, round, flat tablets with beveled edges.

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

Pharmacological properties.

Pharmacodynamics.

Loratadine is a tricyclic selective peripheral H1-histamine receptor antagonist. At the recommended dose, it does not produce clinically significant sedative or anticholinergic effects. During long-term treatment, no clinically significant changes have been observed in vital function parameters, laboratory test results, physical examination findings, or electrocardiograms. Loratadine has no significant effect on H2-histamine receptors. It does not inhibit norepinephrine uptake and has virtually no effect on the cardiovascular system or pacemaker activity.

Skin sensitivity tests to histamine after a single 10 mg dose show that the antihistamine effect begins within 1–3 hours, peaks at 8–12 hours, and lasts more than 24 hours. No tolerance to loratadine was observed after 28 days of treatment.

Clinical efficacy and safety.

More than 10,000 individuals (aged 12 years and older) received loratadine (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 10 mg once daily was more effective than placebo in treating chronic idiopathic urticaria, as demonstrated by reduced itching, erythema, and allergic rash. In these trials, the frequency 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 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, 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 distribution half-life of loratadine and its active metabolite in plasma is approximately 1 hour and 2 hours, respectively.

Metabolism. After oral administration, loratadine is rapidly and well absorbed and extensively metabolized during 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 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 within 10 days, mainly 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 – as loratadine or desloratadine.

In healthy adult volunteers, the elimination half-life of loratadine is 8.4 hours (range 3–20 hours), and that of the main active metabolite is 28 hours (range 8.8–92 hours).

Renal impairment. In patients with chronic renal impairment, AUC and maximum plasma concentration (Cmax) of loratadine and its active metabolite are increased compared to patients with normal renal function. The mean elimination half-life of loratadine and its active metabolite does not differ significantly from that in healthy individuals. Hemodialysis does not affect the pharmacokinetics of loratadine and its active metabolite in patients with chronic liver disease.

Hepatic impairment. In patients with chronic alcoholic liver disease, AUC and Cmax of loratadine are approximately twice as high, while those of its active metabolite are not substantially altered 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 with the severity of liver disease.

Elderly patients. Pharmacokinetic parameters of loratadine and its active metabolite are 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 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 interactions may occur with known inhibitors of CYP3A4 or CYP2D6, leading to increased loratadine levels, which may in turn increase the frequency of adverse reactions.

Increased plasma concentrations of loratadine have been observed after concomitant administration with ketoconazole, erythromycin, and cimetidine, but without clinically significant changes (including on ECG).

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

Special precautions.

Loratadine should be used with caution in patients with severe hepatic impairment.

The product contains lactose. Therefore, patients with rare hereditary conditions such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicinal product.

Loratadine treatment should be discontinued at least 48 hours before skin testing, as antihistamines may neutralize or otherwise reduce positive skin reactivity.

Use during pregnancy or breastfeeding.

Pregnancy. Data on the use of loratadine in pregnant women are very limited. Animal studies have not shown direct or indirect adverse effects related to reproductive toxicity. As a precautionary measure, it is advisable to avoid using loratadine during pregnancy.

Breastfeeding. Data indicate that loratadine/metabolites are excreted into breast milk. Since a risk to the infant cannot be excluded, loratadine should not be used during breastfeeding.

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

Ability to influence reaction rate when driving or operating machinery.

Loratadine has no effect or negligible effect on the ability to drive or operate machinery. However, patients should be informed that somnolence has been very rarely reported, which may affect the ability to drive or operate machinery.

Method of administration and dosage.

Route of administration.

Oral. Tablets may be taken independently of food.

Dosage.

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

For children aged 2 to 12 years, dosage depends on body weight. For body weight >30 kg: 10 mg (1 tablet) once daily. For body weight <30 kg: use syrup formulation.

Elderly patients.

No dose adjustment is required for elderly patients.

Patients with hepatic impairment.

Patients with severe hepatic impairment should receive a lower initial dose due to potentially reduced loratadine clearance. For adults and children with body weight >30 kg, the recommended initial dose is 10 mg every other day.

Patients with renal impairment.

No dose adjustment is necessary for patients with renal impairment.

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

Tablet formulation is indicated for patients with body weight >30 kg.

Overdose.

Overdose of loratadine increases the frequency of anticholinergic symptoms. Somnolence, tachycardia, and headache have been reported in cases 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 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 studies involving adults and adolescents receiving loratadine at the recommended dose of 10 mg daily for indications including allergic rhinitis and chronic idiopathic urticaria, adverse reactions were reported in 2% of patients. The most commonly reported adverse reactions 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, adverse events such as headache (2.7%), nervousness (2.3%), or increased fatigue (1%) were observed.

List of adverse reactions. Adverse reactions reported during the post-marketing period are listed below by system organ class. 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: very rare – anaphylaxis, including 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 – increased fatigue.

Shelf life. 5 years.

Storage conditions.

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

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 operations.

139 Saksaganskogo Street, Kyiv, 01032, Ukraine.