Instructions for Cetrilev Neo film-coated tablets 5 mg blister No. 100
Composition
active ingredient: levocetirizine;
1 tablet contains levocetirizine dihydrochloride 5 mg;
excipients: microcrystalline cellulose, colloidal anhydrous silica, lactose monohydrate, magnesium stearate, Opadry White YS-1-7003 (hypromellose (E 464), titanium dioxide (E 171), polysorbate, macrogol 400).
Dosage form
Film-coated tablets.
Main physicochemical properties: film-coated tablets, white, round, biconvex, with a score, with the inscription "H" on one side and "161" on the other.
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, and has almost no anticholinergic and antiserotonin effects.
Pharmacokinetics.
The pharmacokinetic parameters of levocetirizine are linear and independent of dose and time, with low interpatient variability. The pharmacokinetic profile of the single enantiomer is similar to that of cetirizine. No chiral inversion is observed during absorption or excretion.
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 is reached later. Bioavailability is 100%.
The drug's effect develops 12 minutes after a single dose in 50% of patients, and 0.5–1 hour in 95% of patients. In adults, Cmax in serum is reached 50 minutes after a single oral dose. Steady-state blood concentration is reached after 2 days of taking the drug. Cmax is 207 ng/ml after a single dose and 308 ng/ml after repeated administration of a dose of 5 mg once a day.
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 distribution of levocetirizine is limited, since the volume of distribution is 0.4 l/kg. Binding to human plasma proteins is 90%.
Biotransformation. In humans, the rate of metabolism is less than 14% of the levocetirizine dose, so the difference due to genetic polymorphism or concomitant administration of enzyme inhibitors is likely to be insignificant. The metabolism process includes aromatic oxidation, N- and O-dealkylation and conjugation with taurine. Dealkylation occurs primarily with the participation of cytochrome CYP 3A4, while the aromatic oxidation process 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 exceeding the maximum after taking 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. The drug is excreted in two ways: by glomerular filtration and by active tubular secretion. The plasma half-life (T1/2) of the drug in adults is 7.9 ± 1.9 hours. T1/2 of the drug is shorter in young children. The average apparent 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 clearance of levocetirizine correlates with creatinine clearance. Therefore, in patients with moderate to severe renal impairment, it is recommended that the dosing interval of levocetirizine be adjusted according to creatinine clearance. In anuric patients with end-stage renal disease, total clearance is reduced by approximately 80% compared to that in normal 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
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 with levocetirizine (including CYP3A4 inducers) have not been conducted. Interaction studies with cetirizine (racemate) have shown that concomitant use with antipyrine, azithromycin, cimetidine, diazepam, erythromycin, glipizide, ketoconazole or pseudoephedrine does not produce clinically significant adverse effects. When co-administered with theophylline (400 mg daily), a small decrease (16%) in cetirizine clearance was observed in a multiple-dose study (theophylline distribution was not altered). In a multiple-dose study with ritonavir (600 mg twice daily) and cetirizine (10 mg daily), cetirizine exposure increased by approximately 40%, while the distribution of ritonavir was slightly altered (−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 with alcohol or other central nervous system depressants in susceptible patients may cause additional impairment of attention and ability to perform work.
Reservation
Use with caution in patients with chronic renal failure (dosage regimen adjustment is required); elderly patients (possible decrease in glomerular filtration). During use of the drug, alcohol consumption should be avoided. Food intake does not affect the degree of absorption of the drug, but reduces the rate of its absorption.
When prescribing the drug, the presence of factors predisposing patients to urinary retention (e.g., spinal cord injury, prostatic hyperplasia) should be taken into account, as levocetirizine increases the risk of urinary retention.
Use during pregnancy or breastfeeding.
It is contraindicated for use during pregnancy. The drug is excreted in breast milk, so if it is necessary to use the drug, breastfeeding should be discontinued.
The ability to influence the reaction speed when driving or working with other mechanisms.
You should refrain from driving or operating other machinery during treatment with the drug.
Application features
Use the drug with caution in patients with chronic renal failure (dosage adjustment is 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 patients with factors that provoke urinary retention (e.g., spinal cord injuries, prostatic hyperplasia), it should be taken into account that 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, so 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.
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. It is recommended to prescribe levocetirizine in a dosage form suitable for use in pediatrics to this category of patients.
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
You should refrain from driving or working with other potentially dangerous mechanisms during the period of treatment with 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.
Kidney failure
For patients with renal impairment, the dose calculation should be performed taking into account the degree of renal impairment (creatinine clearance) according to the table (see table below).
To do this, you need to determine the patient's creatinine clearance (CLcr) in ml/min from the serum creatinine content (mg/dl) using the following formula:
| CLcr = | [140 – age (years)] × body weight (kg) | (× 0.85 for women) |
| 72 × serum creatinine (mg/dL) |
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 the use of the drug in children with renal impairment.
Liver failure
No dosage adjustment is required for patients with hepatic insufficiency. Patients with hepatic and renal insufficiency should adjust the dosage 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 less than 4 weeks per year) should be treated according to the course of the disease and the patient's medical history: treatment can be stopped if symptoms disappear and can be resumed if symptoms recur. In case of persistent allergic rhinitis (symptoms present for more than 4 days per week or more than 4 weeks per year), the patient may 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 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. For this category of patients, it is recommended to prescribe levocetirizine in a dosage form suitable for use in pediatrics.
Overdose
Symptoms: Symptoms of overdose in adults may include drowsiness. In children, agitation and increased irritability may occur initially, followed by drowsiness.
Treatment. There is no specific antidote for levocetirizine. In case of symptoms of overdose, symptomatic and supportive therapy is recommended. Gastric lavage may be considered shortly after administration. Hemodialysis is not effective in removing levocetirizine from the body.
Side effects
Immune system disorders: hypersensitivity, including anaphylaxis.
Nutrition and metabolism disorders: increased appetite.
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.
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.
General disorders: edema.
Research results: 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 at a temperature not exceeding 25 °C, out of the reach of children.
Packaging
10 tablets in a blister; 1 or 3 blisters in a cardboard box; 10 tablets in a blister; 1 blister in a cardboard box; 10 cardboard boxes in a cardboard box.
Vacation category
Without a prescription.
Producer
Hetero Labs Limited, India.
Address
Unit III, Formulation Plot No. 22 - 110 IDA, Jeedimetla, Hyderabad, 500 055 Telangana, India.
