Loratadine

Pharmacological properties

loratadine (the active substance of the drug Claritin®) is a tricyclic antihistamine with selective activity against peripheral H1 receptors.

In most patients, when used in the recommended dose, loratadine does not have a clinically significant sedative and anticholinergic effect. During long-term treatment, no clinically significant changes were observed in the indicators of the vital functions of the body, laboratory tests, physical examination or ECG. Loratadine has no significant effect on N₂histamine receptors. The drug does not inhibit the absorption of norepinephrine and does not actually affect the function of the cardiovascular system or the activity of the pacemaker.

Studies with skin tests for histamine after taking a single dose of 10 mg showed that the antihistamine effect occurs after 1-3 hours, reaches a peak after 8-12 hours and lasts more than 24 hours. No development of resistance to the drug after 28 days of using loratadine .

Clinical efficacy and safety. More than 10 thousand people (from the age of 12 years) received loratadine treatment (10 mg tablets) in controlled clinical trials. Loratadine (tablets) at a dose of 10 mg 1 time per day was more effective than placebo and as effective as clemastine in improving the condition for symptoms (nasal and non-nasal) of allergic rhinitis. In these studies, drowsiness occurred at a lower frequency with loratadine than with clemastine, and with almost the same frequency as with terfenadine and placebo.

Among the participants in these studies (from the age of 12), 1 thousand patients with chronic idiopathic urticaria were also registered in placebo-controlled studies. Loratadine in a dose of 10 mg 1 time per day was more effective than placebo in the treatment of chronic idiopathic urticaria, as evidenced by the weakening of itching, erythema and allergic rashes. In these studies, the frequency of drowsiness was similar with loratadine and placebo.

Children. About 200 children (aged 6–12 years) with seasonal allergic rhinitis received loratadine (syrup) in doses of up to 10 mg once a day in controlled clinical trials. In another study, 60 children (aged 2–5 years) received loratadine (syrup) at a dose of 5 mg once a day. No unexpected adverse reactions were observed.

Efficacy in children was similar to that in adults.

Pharmacokinetics Suction. Loratadine is rapidly and well absorbed. The use of the drug during meals may delay the absorption of loratadine, but this does not affect the clinical effect. The bioavailability of loratadine and its active metabolite is proportional to the dose.

Distribution. Loratadine binds actively (from 97 to 99%) with plasma proteins, and its active metabolite with moderate activity (from 73 to 76%).

In healthy volunteers, the half-life of loratadine and its active metabolite in blood plasma is about 1 and 2 hours, respectively.

Biotransformation. After oral administration, loratadine is rapidly and well absorbed, as well as extensively metabolized during the first passage through the liver, mainly with CYP 3A4 and CYP 2D6. The main metabolite desloratadine is pharmacologically active and is more responsible for the clinical effect. Loratadine and desloratadine reach C_max in blood plasma after 1-1.5 hours and 1.5-3.7 hours, respectively, after application of the drug.

About 40% of the dose is excreted in urine and 42% with feces within 10 days, mainly in the form of conjugated metabolites. About 27% of the dose is excreted in the urine during the first 24 hours. Less than 1% of the active substance is excreted in unchanged active form - like loratadine or desloratadine.

In adult healthy volunteers, average T_½ loratadine was 8.4 hours (range from 3 to 20 hours), and the main active metabolite was 28 hours (range from 8.8 to 92 hours).

Impaired renal function. Patients with chronic impaired renal function increased AUC and C_max in blood plasma of loratadine and its active metabolite compared with such indicators in patients with normal renal function. Medium T_½ loratadine and its active metabolite did not differ significantly from those in healthy people. In patients with chronic impaired liver function, hemodialysis does not affect the pharmacokinetics of loratadine and its active metabolite.

Impaired liver function. In patients with chronic alcoholic liver damage, AUC and C indicators_max loratadine were 2 times higher, and their active metabolite did not change significantly when compared with such indicators in patients with normal liver function. T_½ loratadine and its active metabolite is 24 and 37 hours, respectively, and increases depending on the severity of liver disease.

Elderly patients. The pharmacokinetics of loratadine and its active metabolite were similar in healthy adult volunteers and healthy elderly volunteers.

Indications

Tablets: symptomatic treatment of allergic rhinitis and chronic idiopathic urticaria.

Syrup: symptomatic treatment of allergic rhinitis and chronic idiopathic urticaria in adults and children over the age of 2 years.

Application

Tablets. used orally. tablets can be taken regardless of the meal.

Dosage. Adults and children over the age of 12 years - 1 tablet (10 mg of loratadine) should be taken 1 time per day.

In children aged 2 to 12 years, the dose depends on body weight. With a body weight of more than 30 kg: 10 mg (1 tablet) 1 time per day. In children with a body weight of less than 30 kg, a drug in the form of a syrup should be used.

Elderly patients. No dose adjustment is required in the elderly.

Patients with impaired liver function. Patients with severe liver dysfunction should be prescribed the drug in a lower initial dose, since they may have a decrease in clearance of loratadine. For adults and children weighing more than 30 kg, the recommended starting dose is 10 mg every other day.

Patients with impaired renal function. There is no need for dose adjustment in patients with impaired renal function.

Children. The effectiveness and safety of loratadine in children under 2 years of age has not been established. Claritin^®tablets to be prescribed to children weighing more than 30 kg.

Syrup. Apply orally. Syrup can be taken without regard to meals. Adults and children over the age of 12 take 10 ml of syrup (10 mg of loratadine) once a day.

Doses for children aged 2-12 years depend on body weight.

Children weighing more than 30 kg - 10 ml of syrup (10 mg of loratadine) once a day.

Children weighing less than 30 kg - 5 ml of syrup (5 mg of loratadine) 1 time per day.

No dose adjustment is required in the elderly and patients with renal failure. Patients with severely impaired liver function should be given a lower initial dose due to a possible decrease in clearance of loratadine (for adults and children weighing more than 30 kg, the recommended initial dose is 10 mg every other day, and for children with a body weight of up to 30 kg - 5 mg every other day).

Patients with impaired renal function. There is no need for dose adjustment in patients with impaired renal function.

Children. The effectiveness and safety of the drug to children under 2 years of age have not been established.

Contraindications

Hypersensitivity to the active substance or to any other component of the drug.

Side effects

Brief description of the security profile. in clinical studies involving adults and adolescents with the recommended dose of loratadine at a dose of 10 mg / day for indications that include allergic rhinitis and chronic idiopathic urticaria, adverse reactions were reported in 2% of patients (which is higher than in patients receiving placebo). The most common adverse reactions reported more often than with placebo were drowsiness (1.2%), headache (0.6%), increased appetite (0.5%), and insomnia (0.1%) .in clinical trials in children aged 2 to 12 years, adverse events such as headache (2.7%), nervousness (2.3%), or fatigue (1%) were noted.

The list of adverse reactions. Adverse reactions reported during the post-marketing period are indicated by organ system classes. Frequency is defined as: very often (≥1 / 10), often (from ≥1 / 100 to 1/10), infrequently (from ≥1 / 1000 to 1/100), rarely (from ≥1 / 10,000 to 1 / 1000), very rarely (1/10 000) and unknown (it is impossible to establish according to the available data).

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

On the part of the immune system: very rarely - anaphylaxis, including angioedema.

From the nervous system: very rarely - dizziness, convulsions.

From the side of the heart: very rarely - tachycardia, palpitation.

From the digestive tract: very rarely - nausea, dry mouth, gastritis.

From the hepatobiliary system: very rarely - pathological changes in liver function.

On the part of the skin and subcutaneous tissue: very rarely - rash, alopecia.

General disorders and associated with the method of use of the drug: very rarely - fatigue.

special instructions

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

The composition of the drug in the form of tablets includes lactose. For this reason, patients with rare inherited diseases such as galactose intolerance, Lapp lactase deficiency and glucose-galactose malabsorption should not use this drug.

Claritin Syrup^® contains 3 g of sucrose in 5 ml; 6 g of sucrose in 10 ml. Use with caution in patients with diabetes. May be harmful to teeth. Claritin Syrup^® should not be prescribed to patients with a rare hereditary impairment of fructose tolerance, galactose, hereditary lactase deficiency, glucose-galactose malabsorption syndrome or sucrose-isomaltase deficiency. If intolerance to certain sugars is detected, you should consult your doctor before taking the drug.

The use of the drug Claritin^® it must be stopped at least 48 hours before skin tests, as antihistamines can neutralize or otherwise weaken the positive reaction when determining the skin reactivity index.

Use during pregnancy or lactation. Pregnancy. There is very little data on the use of loratadine in pregnant women. Animal studies have not revealed direct or indirect negative effects regarding reproductive toxicity. It is advisable, as a safety measure, to avoid the use of the drug Claritin^® during pregnancy.

Lactation. Physico-chemical data indicate the release of loratadine / metabolites with breast milk. Since the risk to the child cannot be excluded, the drug Claritin^® should not be used during lactation.

Fertility. Data on the effect of the product on female or male fertility are not available.

The ability to influence the reaction rate when driving vehicles or other mechanisms. Claritin^® does not or does not significantly affect the ability to drive vehicles or other mechanisms. However, the patient must be informed that drowsiness is very rare, which may affect the ability to drive vehicles or mechanisms.

Interactions

With simultaneous use with alcohol, the effects of the drug Claritin® are not enhanced, as confirmed by studies of psychomotor function.

Potential interaction is possible with all known CYP 3A4 or CYP 2D6 inhibitors, which leads to an increase in the level of loratadine, and this, in turn, can cause an increase in the incidence of adverse reactions.

In controlled studies, an increase in the concentration of loratadine in blood plasma after simultaneous use with ketoconazole, erythromycin and cimetidine was reported, which was not accompanied by clinically significant changes (including ECG).

Children. Studies of interaction with other drugs were carried out only with the participation of adult patients.

Overdose

An overdose of loratadine increases the incidence of anticholinergic symptoms. with an overdose, drowsiness, tachycardia, and headache were reported. in case of overdose, symptomatic and supportive treatment is recommended for the required period. it is possible to use activated carbon in the form of an aqueous suspension. gastric lavage can also be performed. loratadine is not excreted during hemodialysis; the effectiveness of peritoneal dialysis in drug excretion is unknown. after emergency care, the patient should remain under medical supervision.

Storage conditions

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