Instructions for use Alerzin film-coated tablets 5 mg blister No. 7
Composition
active ingredient: levocetirizine dihydrochloride;
1 tablet contains 5 mg of levocetirizine dihydrochloride (corresponding to 4.21 mg of levocetirizine);
excipients: microcrystalline silicon cellulose, low-substituted hydroxypropyl cellulose, lactose monohydrate, magnesium stearate;
shell composition: Opadry II 33G28523 white (hypromellose, titanium dioxide (E 171), macrogol 3350, triacetylglycerol, lactose monohydrate).
Dosage form
Film-coated tablets.
Main physicochemical properties: white or almost white, round, moderately biconvex tablets, film-coated, odorless or almost odorless, engraved with the stylized letter "E" on one side and the number "281" on the other.
Pharmacotherapeutic group
Antihistamines for systemic use. Piperazine derivatives. ATX code R06A E09.
Pharmacological properties
Pharmacodynamics
Levocetirizine is the active, stable R-enantiomer of cetirizine, which belongs to the group of competitive histamine antagonists. The pharmacological action is due to the blockade of
H1-histamine receptors. The affinity for H1-histamine receptors of levocetirizine is 2 times higher than that of cetirizine. It affects the histamine-dependent stage of the development of an allergic reaction, reduces eosinophil migration, vascular permeability, limits the release of inflammatory mediators. It prevents the development and alleviates the course of allergic reactions, has antiexudative, antipruritic, anti-inflammatory effects, and has almost no anticholinergic and antiserotonin effects.
Pharmacokinetics
The pharmacokinetic parameters of levocetirizine are linear and almost do not differ from those of cetirizine.
Absorption. The drug is rapidly and extensively absorbed after oral administration. The extent of absorption of the drug does not depend on the dose of the drug and does not change with food intake, but the maximum concentration (Cmax) of the drug decreases and reaches its maximum value later. Bioavailability reaches 100%.
In 50% of patients, the effect of the drug develops 12 minutes after taking a single dose, and in 95% - after 0.5-1 hour. Cmax in blood serum is reached 50 minutes after a single oral dose and is maintained for 2 days. Cmax is 270 ng/ml after a single dose and 308 ng/ml after repeated use at a dose of 5 mg, respectively.
Distribution. There is no information on the distribution of the drug in human tissues, as well as on the penetration of levocetirizine through the blood-brain barrier. In studies, the highest concentration was recorded in the liver and kidneys, and the lowest - in the tissues of the central nervous system. The volume of distribution is 0.4 l/kg. Binding to plasma proteins is 90%.
Biotransformation. Approximately 14% of levocetirizine is metabolized in humans. The metabolic pathway includes oxidation, N- and O-dealkylation, and conjugation with taurine. Dealkylation is primarily mediated by cytochrome CYP 3A4, while oxidation involves multiple and/or unidentified CYP isoforms. Levocetirizine does not affect the activity of cytochrome isoenzymes 1A2, 2C9, 2C19, 2D6, 2E1, 3A4 at concentrations significantly above the maximum after a 5 mg oral dose. Given the low degree of metabolism and the lack of ability to inhibit metabolism, interactions of levocetirizine with other substances (and vice versa) are unlikely.
Excretion. The drug is excreted mainly by glomerular filtration and active tubular secretion. The plasma half-life of the drug in adults (T1/2) is 7.9 + 1.9 hours. T1/2 is shorter in young children. Total clearance in adults is 0.63 ml/min/kg. Levocetirizine and its metabolites are mainly excreted in the urine (an average of 85.4% of the administered dose is excreted). Only 12.9% of the administered dose is excreted in the feces.
Special populations
Kidney dysfunction
The apparent body clearance of levocetirizine correlates with creatinine clearance. Therefore, in patients with moderate to severe renal impairment, it is recommended to adjust the dosing intervals of levocetirizine based on creatinine clearance. In anuric patients with end-stage renal disease, the total body clearance is reduced by approximately 80% compared to that in healthy subjects. The amount of levocetirizine removed during a standard 4-hour hemodialysis session was < 10%.
Indication
Symptomatic treatment of allergic rhinitis (including perennial allergic rhinitis) and urticaria.
Contraindication
Hypersensitivity to levocetirizine, cetirizine, hydroxyzine, to any other piperazine derivatives or to any other excipient of the drug.
Severe chronic renal failure (creatinine clearance <10 ml/min).
Rare hereditary diseases of galactose intolerance, lactase deficiency or glucose-galactose malabsorption.
Interaction with other medicinal products and other types of interactions
Interaction studies (including studies with CYP3A4 inducers) have not been conducted with levocetirizine.
Studies with cetirizine (racemate) have shown that concomitant use with antipyrine, azithromycin, cimetidine, diazepam, erythromycin, glipizide, ketoconazole or pseudoephedrine does not cause clinically significant adverse interactions. Co-administration with theophylline (400 mg daily) reduces the total clearance of levocetirizine by 16% (theophylline kinetics are not changed). In a study of multiple doses of ritonavir (600 mg twice daily) and cetirizine (10 mg daily), the exposure of cetirizine increased by approximately 40%, while the distribution of ritonavir was slightly altered (-11%) by concomitant administration of cetirizine.
There is no evidence of an increase in the effect of sedatives when used in therapeutic doses. However, the use of sedatives should be avoided while taking the drug.
Levocetirizine does not enhance the effect of alcohol, however, in sensitive patients, the simultaneous use of Alerzin and alcohol or other drugs that suppress the function of the central nervous system may affect the function of the central nervous system.
Food intake does not affect the extent of absorption of the drug, but simultaneous intake of food reduces the rate of its absorption.
Application features
Use the drug with caution in patients with chronic renal failure (dosage adjustment is necessary) and in elderly patients with renal failure (possible decrease in glomerular filtration). During use of the drug, alcohol consumption should be avoided.
If patients have certain factors that provoke urinary retention (e.g. spinal cord injuries, prostatic hyperplasia), care should be taken when determining the dose of the drug, as levocetirizine may increase the risk of urinary retention.
Levocetirizine should be used with caution in patients with epilepsy and at risk of seizures, as its use may lead to increased seizures.
Antihistamines suppress the response to skin allergy testing, so before conducting it, the drug must be stopped 3 days before the test (withdrawal period).
Itching may occur after stopping levocetirizine, even if these symptoms were not present before starting treatment. The symptoms may disappear on their own. In some cases, the symptoms may be intense and re-treatment may be necessary. Only when the symptoms disappear should treatment be restarted.
The drug in tablet form is not used in children under 6 years of age, since this dosage form does not allow for the necessary correction of the dosage regimen. It is recommended to prescribe levocetirizine in a dosage form suitable for use in pediatrics for this category of patients.
Ability to influence reaction speed when driving vehicles or other mechanisms
You should refrain from driving or operating other machinery during treatment with the drug.
Use during pregnancy or breastfeeding
Use during pregnancy or breastfeeding
Levocetirizine is contraindicated for use during pregnancy. Levocetirizine passes into breast milk, so if necessary, breastfeeding should be discontinued.
Fertility
There are no clinical data (including animal studies) on the effects of levocetirizine on fertility.
Method of administration and doses
The drug is prescribed to adults and children over 6 years of age.
Recommended doses:
Adults and children over 12 years of age: the daily dose is 5 mg (1 film-coated tablet) once a day.
Elderly patients
No dose adjustment is required in elderly patients with normal renal function. Dose adjustment is recommended in elderly patients with moderate to severe renal impairment (see Renal impairment).
Kidney failure
For patients with impaired renal function, the dose calculation should be carried out taking into account creatinine clearance according to the table.
To use this dosing table, it is necessary to estimate the patient's creatinine clearance (CLcr) in milliliters per minute. CLcr (mL/min) is estimated from serum creatinine (mg/dL) using the following formula:
CLcr = [140 – age (years)] x body weight (kg) / 72 x serum creatinine (mg/dL) (x 0.85 for women)
Dosage adjustment for patients with renal impairment
| Kidney function | Creatinine clearance, ml/min | Dosage and number of doses |
| Normal kidney function | ≥ 80 | 5 mg once daily |
| Mild impairment | 50-79 | 5 mg once daily |
| Moderate impairment | 30-49 | 5 mg once every 2 days |
| Severe violation | < 30 | 5 mg once every 3 days |
End-stage kidney disease. Patients on dialysis | < 10 | Contraindicated |
For children with impaired renal function, the dose of the drug should be adjusted individually, taking into account renal clearance and body weight.
There are no specific data on use in children with renal impairment.
No dosage adjustment is required for patients with hepatic insufficiency. For patients with hepatic and renal insufficiency, the dosage should be adjusted according to the table above.
Pediatric population
Children aged 6 to 12 years: the recommended daily dose is 5 mg (1 film-coated tablet).
For children aged 2 to 6 years, it is not possible to adjust the dose of the drug in the film-coated tablet dosage form. It is recommended to prescribe levocetirizine in a dosage form suitable for use in pediatrics.
Method of application
Take the tablet orally, regardless of food intake. The tablet should be swallowed whole, with a small amount of water. It is recommended to take the daily dose in one go.
Duration of use
Patients with intermittent allergic rhinitis (symptoms present for less than 4 days per week or for less than 4 weeks per year) should be treated according to the disease and history; treatment can be discontinued if symptoms resolve and can be resumed if symptoms recur. In case of persistent allergic rhinitis (symptoms present for more than 4 days per week and for more than 4 weeks per year), the patient may be offered continuous therapy during the period of exposure to allergens. There is clinical experience with levocetirizine for a treatment period of at least 6 months.
In chronic diseases (chronic allergic rhinitis, chronic urticaria), the duration of treatment is up to 1 year (data are available from clinical studies using cetirizine (racemate)).
Children
The drug in tablet form should not be used in children under 6 years of age, as this dosage form does not allow for the necessary correction of the dosage regimen. For this category of patients, it is recommended to use levocetirizine in a dosage form suitable for use in pediatrics.
Overdose
Symptoms: Symptoms of overdose may include drowsiness in adults and initial agitation and increased irritability followed by drowsiness in children.
Treatment. There is no specific antidote for levocetirizine. In case of symptoms of overdose, symptomatic and supportive therapy is recommended. Gastric lavage should be considered shortly after ingestion. Hemodialysis is not effective in removing levocetirizine from the body.
Adverse reactions
Nervous system: drowsiness, headache, fatigue, weakness, asthenia, convulsions, paresthesia, dizziness, fainting, tremor, dysgeusia.
Psychiatric: sleep disturbances, agitation, hallucinations, depression, aggression, insomnia, suicidal thoughts, nightmares.
Cardiac: palpitations, tachycardia.
On the part of the organs of vision: visual impairment, blurred vision, oculogyration.
From the organs of hearing and balance: vertigo.
Hepatobiliary disorders: hepatitis.
Renal and urinary disorders: dysuria, urinary retention.
Immune system disorders: hypersensitivity, including anaphylaxis.
Respiratory, thoracic and mediastinal disorders: dyspnea.
Gastrointestinal: diarrhea, vomiting, constipation, dry mouth, nausea, abdominal pain.
Skin and subcutaneous tissue disorders: angioedema, persistent drug eruptions, pruritus, rash, urticaria.
Musculoskeletal, connective tissue and bone disorders: myalgia, arthralgia.
Research results: weight gain, abnormal liver function tests.
Nutrition and metabolism disorders: increased appetite.
General disorders: edema.
The drug should be discontinued if any of the above side effects occur and when the cause of its development cannot be clearly established.
Description of selected adverse reactions
Pruritus has been reported after discontinuation of levocetirizine.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after the approval of a medicine is very important. This allows the benefit/risk balance of the medicine to be monitored. Healthcare professionals are asked to report suspected adverse reactions.
Expiration date
5 years.
Do not use after the expiry date stated on the packaging.
Storage conditions
Store in the original packaging at a temperature not exceeding 30 °C, out of the reach of children.
Packaging
7 tablets in a blister, 1 blister in a cardboard box.
Vacation category
Without a prescription.
Producer
CJSC Pharmaceutical Plant EGIS, Hungary.
Location of the manufacturer and its business address
1165, Budapest, Bekenfeldi Street, 118-120, Hungary.
