Instructions for use Kontrahist Allergy film-coated tablets 5 mg blister No. 10
Composition
active ingredient: levocetirizine;
1 tablet contains levocetirizine dihydrochloride 5 mg;
excipients: microcrystalline cellulose, lactose monohydrate, magnesium stearate;
mixture for applying the film coating: hypromellose (E 464), macrogol 400, titanium dioxide (E 171).
Dosage form
Film-coated tablets.
Main physicochemical properties: film-coated tablets, white, biconvex, oblong (length 8 mm, width 4.5 mm), engraved 'ᶺ 11' on one side, without visible impurities or contaminants.
Pharmacotherapeutic group
Antihistamines for systemic use. Piperazine derivatives. ATX code R06A E09.
Pharmacological properties
Pharmacodynamics.
Levocetirizine is an 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 suppresses the course of allergic reactions, has antiexudative, antipruritic, anti-inflammatory effects, almost does not have anticholinergic and antiserotonin effects. In therapeutic doses, it almost does not show a 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 is independent of the dose and does not change with food intake, but the maximum concentration of the drug (Cmax) 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 of the therapeutic dose. Equilibrium concentration in the blood is reached after 2 days of taking the drug. 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 animal 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, 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 is unlikely.
Breeding
Excretion of the drug occurs mainly due to 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 of the drug 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.
The average total clearance is 0.63 ml/min/kg. Therefore, in patients with moderate to severe renal impairment, it is recommended to adjust the dosing intervals of levocetirizine based on creatinine clearance. In patients with anuria in end-stage renal disease, the total clearance of the patient is reduced by approximately 80% compared to that of the 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 the drug, as well as to any piperazine derivatives.
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. When co-administered with theophylline (400 mg daily), a small decrease (16%) in the total clearance of levocetirizine was observed (theophylline distribution was 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 changed (-11%) with concomitant use 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.
Food intake does not affect the extent of absorption of the drug, but simultaneous intake of food reduces the rate of its absorption.
Concomitant use of cetirizine or levocetirizine and alcohol or other central nervous system depressants in susceptible patients may cause additional impairment of alertness and ability to perform work.
Application features
Use with caution in patients with chronic renal failure (dose adjustment required) and in elderly patients with renal failure (possible reduction in glomerular filtration). Alcohol consumption should be avoided during use of the drug (see section "Interaction with other medicinal products and other types of interactions").
When prescribing the drug to a patient, it is necessary to pay attention to the presence of certain factors that provoke urinary retention (for example, spinal cord injuries, prostatic hyperplasia), since levocetirizine increases 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; the drug should be discontinued 3 days before testing (withdrawal period).
Itching may occur after discontinuation of levocetirizine, even if this symptom was not present before treatment. The symptom may disappear on its own. In some cases, the symptom may be intense and re-treatment may be necessary. The symptom should disappear after re-treatment.
Use during pregnancy or breastfeeding
Levocetirizine is contraindicated for use during pregnancy. Cetirizine 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.
Ability to influence reaction speed when driving vehicles or other mechanisms
Comparative clinical studies have not revealed any evidence that levocetirizine at the recommended dose impairs mental alertness, reaction time or the ability to drive.
However, some patients may experience drowsiness, fatigue and asthenia during levocetirizine therapy. Therefore, patients who intend to drive a car, engage in potentially hazardous activities or operate machinery should take into account their reaction to the drug.
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
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 Renal impairment section).
Kidney failure
For patients with renal impairment, the dose should be calculated taking into account the degree of renal impairment (creatinine clearance) according to the table below.
To use this dosing table, it is necessary to estimate the patient's creatinine clearance (CLcr) in mL/min. CLcr (mL/min) is estimated from serum creatinine (mg/mL) using the formula:
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 renal disease Patients on dialysis | < 10 | Contraindicated |
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 (duration of symptoms < 4 days per week or less than 4 weeks) should be treated according to the disease and history; treatment can be stopped if symptoms disappear and can be resumed again if symptoms recur. In case of persistent allergic rhinitis (duration of symptoms > 4 days per week and more than 4 weeks) the patient may be offered continuous therapy during the period of contact with allergens. In chronic diseases (chronic allergic rhinitis, chronic urticaria) the duration of treatment is up to 1 year (data are available from clinical studies using the 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. Levocetirizine in a dosage form suitable for use in pediatrics is recommended for this category of patients.
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 administration. Hemodialysis is not effective in removing levocetirizine from the body.
Side effects
The following adverse reactions were reported in clinical trials with levocetirizine in at least 1% of patients (common (≥ 1/100, < 1/10)) aged 12 to 71 years:
from the nervous system: headache, drowsiness;
From the digestive tract: dry mouth;
on the part of the body as a whole: increased fatigue.
Asthenia and abdominal pain have also been reported uncommonly (≥ 1/1000, < 1/100).
The following adverse reactions have been reported in clinical trials of levocetirizine in at least 1% of children aged 6 to 11 months and in children aged 1 to 6 years:
from the digestive tract: diarrhea, vomiting, constipation;
from the nervous system: drowsiness;
Psychiatric: sleep disorders.
The following adverse reactions have been reported in at least 1% of children aged 6 to 12 years during clinical trials with levocetirizine:
from the nervous system: headache, drowsiness.
The main adverse reactions and their frequencies identified in clinical trials and/or from post-marketing experience are summarized below.
The frequency is classified as follows: very common (≥ 1/10), common (≥ 1/100 and < 1/10), uncommon (≥ 1/1000 and < 1/100), rare (≥ 1/10000 and < 1/1000), very rare (< 1/10000), frequency unknown (frequency cannot be estimated from the available data).
Immune system disorders: frequency unknown: hypersensitivity, including anaphylaxis.
Nutrition and metabolism disorders: frequency unknown: increased appetite.
Nervous system: frequency unknown: drowsiness, headache, fatigue, weakness, asthenia, convulsions, paresthesia, dizziness, fainting, tremor, dysgeusia.
Psychiatric: frequency unknown: sleep disturbances, agitation, hallucinations, depression, aggression, insomnia, suicidal thoughts, nightmares.
Cardiac disorders: frequency unknown: palpitations, tachycardia.
On the part of the organs of vision: frequency unknown: visual disturbances, blurred vision, eye rolling.
From the side of the organs of hearing and balance: frequency unknown: vertigo.
Hepatobiliary disorders: frequency unknown: hepatitis.
Renal and urinary disorders: frequency unknown: dysuria, urinary retention.
Respiratory, thoracic and mediastinal disorders: frequency unknown: shortness of breath.
Gastrointestinal: frequency unknown: nausea, diarrhea, vomiting; constipation, dry mouth, abdominal pain.
Skin and subcutaneous tissue disorders: frequency unknown: angioedema, persistent drug eruptions, pruritus, rash, urticaria.
Musculoskeletal, connective tissue and bone disorders: frequency unknown: myalgia, arthralgia.
General disorders and administration site conditions: frequency unknown: edema.
Research results: frequency unknown: weight gain, abnormal liver function tests.
Description of selected adverse reactions
Pruritus has been reported after discontinuation of levocetirizine.
Reporting suspected adverse reactions after a medicinal product has been authorised is very important. This allows for continuous monitoring of the benefit/risk balance of the product. Healthcare professionals are asked to report suspected adverse reactions.
Expiration date
3 years.
Storage conditions
Store in the original packaging out of the reach of children, at a temperature not exceeding 25 °C.
Packaging
10 tablets in a blister; 1 blister in a cardboard box.
7 tablets in a blister; 1 blister in a cardboard box.
Vacation category
Without a prescription.
Producer
Adamed Pharma JSC, Poland.
Location of the manufacturer and address of its place of business.
St. Marsh. J. Pilsudskiego 5, 95-200, Pabianice, Poland.
