Instructions for use Alerzin oral drops 5 mg/ml bottle with dropper 20 ml
Composition
active ingredient: levocetirizine dihydrochloride;
1 ml contains 5 mg of levocetirizine dihydrochloride (equivalent to 4.21 mg of levocetirizine);
excipients: glycerin 85%, propylene glycol, sodium saccharin, sodium acetate trihydrate, methyl parahydroxybenzoate (E 218), propyl parahydroxybenzoate (E 216), glacial acetic acid, purified water.
Dosage form
Oral drops, solution.
Main physicochemical properties: colorless or almost colorless sweet liquid without sediment, with a faint odor of acetic acid.
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 blocking 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, has almost no anticholinergic and antiserotonin effects. In therapeutic doses, it has almost no sedative effect.
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 occurs primarily with the participation of 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, and 3A4 at concentrations significantly higher than the maximum after a 5 mg oral dose. Given the low degree of metabolism and the lack of ability to inhibit metabolism, the interaction of levocetirizine with other substances (and vice versa) is unlikely.
Excretion. Excretion of the drug occurs mainly by glomerular filtration and active tubular secretion. The half-life of the drug from blood plasma 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 or to any other component of this dosage form, or to any piperazine derivatives.
Severe chronic renal failure (creatinine clearance <10 ml/min).
Interaction with other medicinal products and other types of interactions
Interaction studies with levocetirizine (including studies with CYP3A4 inducers) have not been conducted. 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
The drug should be used with caution in patients with chronic renal failure (dosage adjustment is necessary), in elderly patients (possible decrease in glomerular filtration). The drug should be used with caution when taken simultaneously with alcohol (see section "Interaction with other medicinal products and other types of interactions").
Eating does not affect the extent of absorption, but reduces its rate.
If patients have certain factors that provoke urinary retention (e.g., spinal cord injuries, prostatic hyperplasia), care should be taken when prescribing the drug, as levocetirizine may increase the risk of urinary retention.
Methyl parahydroxybenzoate and propyl parahydroxybenzoate, which are part of the oral drops, may cause allergic reactions (possibly delayed).
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 it may be necessary to re-apply the treatment after stopping it. Only if the symptoms disappear should the treatment be restarted.
Use during pregnancy or breastfeeding
Levocetirizine is contraindicated for use during pregnancy. Levocetirizine is excreted in 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.
Ability to influence reaction speed when driving vehicles or other mechanisms
You should refrain from driving or operating other machinery while using the drug.
Method of administration and doses
The drug is prescribed to adults and children aged 2 years and older.
Recommended doses:
Adults and adolescents aged 12 years and over: the recommended daily dose of the drug is 5 mg (20 drops) once a day.
Elderly patients
Elderly patients with normal renal function do not require dose adjustment.
Dose adjustment is recommended for elderly patients with moderate to severe renal impairment (see section "Renal impairment").
Kidney failure
Elderly patients with normal renal function do not require dose adjustment.
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 the patient's 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
Recommended doses:
Children aged 2 to 6 years: the recommended daily dose of the drug is 2.5 mg (10 drops). The indicated dose should be administered at 1.25 mg (5 drops) 2 times a day;
Children aged 6 to 12 years: the recommended daily dose of the drug is 5 mg (20 drops) once a day.
Method of application
Drops should be dripped into a spoon or dissolved in a small amount of water and taken orally. When diluting the drops, it should be taken into account (especially when used in children) that the volume of water to which the drops are added should correspond to the amount of liquid that the patient can swallow. The diluted solution should be taken immediately.
When counting drops, the bottle should be held vertically (bottom up). If there is no flow of drops (if the appropriate number of drops was not obtained), the bottle should be turned upside down and then upside down again and continue counting drops.
The drug can be taken regardless of food intake.
Duration of use
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 can be offered continuous therapy during the period of contact with 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 with cetirizine (racemate)).
Children
The use of levocetirizine in children under 2 years of age is not recommended due to limited data in this age group.
The drug should be used in children over 2 years of age.
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 ineffective for removing levocetirizine from the body.
Side effects
Nervous system: drowsiness, headache, fatigue, weakness, asthenia, convulsions, paresthesia, dizziness, fainting, tremor, dysgeusia.
Psychiatric: sleep disturbances, agitation, hallucinations, depression, aggression, insomnia, suicidal thoughts.
Cardiac: palpitations, tachycardia.
On the part of the organs of vision: visual impairment, blurred vision.
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.
On the part of the digestive tract: diarrhea, vomiting, constipation, dry mouth, nausea, abdominal pain.
Skin and subcutaneous tissue disorders: angioedema, persistent drug eruptions, pruritus, rash, urticaria.
Musculoskeletal system: myalgia, arthralgia.
Research results: increased body weight, deviation of liver function tests from normal values.
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.
Methyl parahydroxybenzoate and propyl parahydroxybenzoate, which are part of the oral drops, may cause allergic reactions (possibly delayed).
Description of selected adverse reactions
Pruritus has been reported after discontinuation of levocetirizine.
Adverse reaction reporting
Reporting of suspected adverse reactions after the approval of a medicinal product is important. This allows for continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system.
Expiration date
4 years.
After opening the bottle, store for no more than 6 weeks.
Storage conditions
Store at a temperature not exceeding 25 °C out of the reach of children.
Do not freeze!
Packaging
20 ml of solution in brown glass bottles with a polyethylene dropper;
1 bottle in a cardboard box.
Vacation category
Without a prescription.
Producer
CJSC Pharmaceutical Plant EGIS, Hungary.
9900, Kermend, Matyas Kirai Street 65, Hungary.
