Loratadine

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT LORATADINE (LORATADIN)

Composition:

Active substance: loratadine;

1 ml of syrup contains 1 mg of loratadine;

Excipients: propylene glycol; sodium saccharin; glycerin; citric acid monohydrate; sorbitol solution, non-crystallizing (containing E 420); methylparahydroxybenzoate (E 218); propylparahydroxybenzoate (E 216); "Wild Strawberry" flavoring (containing: Ponceau 4R (E 124), Azorubine E 122)); purified water.

Pharmaceutical form. Syrup.

Main physicochemical properties: clear, syrup-like, bright red liquid with a characteristic odor and sour-sweet taste.

Pharmacotherapeutic group. Antihistamines for systemic use.

ATC code R06A X13.

Pharmacological properties.

Pharmacodynamics.

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

When used at the recommended dose, it 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 receptor activity. It does not inhibit norepinephrine uptake and has virtually no effect on the cardiovascular system or pacemaker activity.

After a single 10 mg dose, skin sensitivity tests to histamine demonstrated that the antihistaminic effect becomes clinically evident within 1–3 hours, reaches its peak between 8 and 12 hours after administration, and lasts for 24 hours. There was no evidence of tachyphylaxis during 28 days of continuous treatment.

Pharmacokinetics.

Absorption. Following oral administration, loratadine is rapidly and well absorbed. Food intake slightly prolongs the absorption period of loratadine but does not affect its clinical efficacy. The bioavailability of loratadine and its active metabolite, desloratadine, is directly proportional to the dose.

Distribution. Loratadine is highly bound (97–99%) to plasma proteins, while its active metabolite is moderately bound (73–76%). The elimination half-life of loratadine and its active metabolite in plasma in healthy volunteers is approximately 1 hour and 2 hours, respectively, after administration.

Metabolism. After oral administration, loratadine is rapidly and well absorbed and metabolized primarily by CYP3A4 and CYP2D6 enzymes into desloratadine. The main metabolite, desloratadine, is pharmacologically active and largely responsible for the clinical effect. The time to reach maximum plasma concentration (T_max) is 1–1.5 hours for loratadine and 1.5–3.7 hours for desloratadine.

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

The mean terminal elimination half-life in healthy adult volunteers is 8.4 hours (range: 3–20 hours) for loratadine and 28 hours (range: 8.8–92 hours) for its main active metabolite.

Renal impairment. In patients with impaired renal function, the area under the plasma concentration-time curve (AUC) and maximum plasma concentration (C_max) of loratadine and its active metabolite are higher than in patients with normal renal function. The mean elimination half-life of loratadine and its active metabolite does not differ significantly from that in healthy volunteers. In patients with chronic renal impairment, hemodialysis does not significantly affect the pharmacokinetics of loratadine or its active metabolite.

Hepatic impairment. In patients with chronic alcoholic liver disease, AUC and C_max values for loratadine are approximately twice as high as in patients with normal liver function, while the corresponding values for the active metabolite do not change significantly. 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 are similar in healthy adult volunteers, including elderly individuals.

Clinical characteristics.

Indications.

Symptomatic treatment of allergic rhinitis and chronic idiopathic urticaria.

Contraindications.

Hypersensitivity to loratadine or to any of the excipients of the medicinal product.

Interaction with other medicinal products and other forms of interaction.

Loratadine does not enhance the central nervous system depressant effect of alcohol on psychomotor performance.

Concomitant use of loratadine with CYP3A4 or CYP2D6 inhibitors may lead to increased loratadine levels, which in turn may enhance adverse effects.

Concomitant administration of the drug with ketoconazole, erythromycin, or cimetidine has been associated with increased plasma concentrations of loratadine; however, this increase was not clinically significant, including no changes observed on electrocardiograms.

Children.

Studies on drug interactions have been conducted only in adult patients.

Special precautions for use.

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

If intolerance to certain sugars has been established, a physician should be consulted before taking this medicinal product.

The medication should be discontinued no later than 48 hours prior to skin allergy testing to prevent false test results.

Loratadine contains azo dyes (azorubine and Ponceau 4R) as well as methylparahydroxybenzoate and propylparahydroxybenzoate, which may cause allergic reactions (possibly delayed).

Use during pregnancy or breastfeeding.

Pregnancy. There is very limited data on the use of loratadine in pregnant women. As a precautionary measure, it is advisable to avoid using loratadine during pregnancy.

Breastfeeding. Physicochemical data indicate that loratadine and its metabolites are excreted in 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 drug on male or female fertility.

Ability to influence the reaction rate while 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 very rarely reported, which may affect the ability to drive or operate machinery.

Method of administration and dosage.

Method of administration.

For oral use. The syrup can be taken regardless of food intake.

Dosing.

Adults and children aged 12 years and older: take 10 mL of syrup (10 mg of loratadine) once daily.

Dosing for children aged 2 to 12 years depends on body weight.

Children with body weight above 30 kg: 10 mL of syrup (10 mg of loratadine) once daily.

Children with body weight up to 30 kg: 5 mL of syrup (5 mg of loratadine) once daily.

Elderly patients.

Dosage adjustment is not required for elderly individuals.

Patients with hepatic impairment.

Patients with severe hepatic impairment should be given 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; for children with body weight up to 30 kg, the recommended initial dose is 5 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.

Overdose.

In cases of overdose, anticholinergic symptoms have been observed: drowsiness, tachycardia, and headache. Symptomatic and supportive treatment is recommended for the required duration. Standard measures for removal of the unabsorbed drug from the stomach are advised: gastric lavage and administration of powdered activated charcoal with water.

Loratadine is not removed by hemodialysis; it is also unknown whether loratadine is removed by peritoneal dialysis.

After emergency treatment, the patient should remain under medical supervision.

Adverse reactions

In children aged 2 to 12 years, the following adverse events were observed: headache, nervousness, or increased fatigue.

In adults and children aged 12 years and older, somnolence, headache, increased appetite, and insomnia were observed.

The frequency of adverse reactions was defined as follows: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000), very rare (<1/10,000), and frequency not known (cannot be estimated from the available data).

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

Shelf life. 3 years.

Storage conditions. Store at a temperature not exceeding 25 °C in a place inaccessible to children.

Packaging. 90 ml in a bottle or jar with a dosing cup in a carton.

Prescription status. Over-the-counter.

Manufacturer.

LLC "DKP "Pharmaceutical Factory".

Manufacturer's address and place of business.

4, Korolova St., Stanishivka village, Zhytomyr district, Zhytomyr region, 12430, Ukraine.