Instructions for L-cet film-coated tablets 5 mg No. 100
Composition
active ingredient: levocetirizine dihydrochloride;
1 film-coated tablet contains levocetirizine dihydrochloride 5 mg;
excipients: microcrystalline cellulose, croscarmellose sodium, magnesium stearate, colloidal anhydrous silicon dioxide, Opadry II 85G51300 green*;
*Opadry II 85G51300 green: polyvinyl alcohol, talc, titanium dioxide (E 171), polyethylene glycol, lecithin, indigo carmine (E 132), quinoline yellow (E 104), sunset yellow FCF (E 110).
Dosage form
Film-coated tablets.
Main physicochemical properties: round biconvex tablets, coated with a green film.
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 antagonists of peripheral 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, independent of dose and time, and have 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.
Levocetirizine is rapidly and extensively absorbed after oral administration. The extent of absorption is independent of dose and does not change with food intake, but the maximum concentration (Cmax) of the drug decreases and reaches its maximum value later. Bioavailability is 100%.
In 50% of patients, the effect of levocetirizine develops 12 minutes after taking a single dose, and in 95% - after 0.5-1 hour. The maximum concentration (Cmax) in the blood serum is reached 50 minutes after a single oral dose. The equilibrium concentration in the blood is reached after two 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 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 plasma proteins is 90%.
Biotransformation.
In humans, the rate of metabolism is less than 14% of the levocetirizine dose, and therefore the difference resulting from genetic polymorphism or concomitant administration of enzyme inhibitors is expected 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 did not affect the activity of cytochrome isoenzymes 1A2, 2C9, 2C19, 2D6, 2E1, 3A4 at concentrations significantly exceeding 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.
Breeding.
Excretion of the drug occurs mainly by glomerular filtration and active tubular secretion. The half-life of levocetirizine from blood plasma in adults (T1/2) is 7.9 ± 1.9 hours. The half-life 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 of levocetirizine 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 the total body clearance 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).
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. With concomitant use with theophylline (400 mg/day), a small decrease (by 16%) in the total clearance of levocetirizine was observed (theophylline distribution was not changed). In a study of multiple doses of ritonavir (600 mg 2 times a day) and cetirizine (10 mg per day), the extent of exposure to cetirizine increased by approximately 40%, while the distribution of ritonavir was slightly changed (-11%) with concomitant use of cetirizine.
Food intake does not affect the extent of absorption of the drug, but 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 (dosage adjustment required) and in elderly patients (possible reduction 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").
When prescribing the drug in patients with certain 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.
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.
Since antihistamines can suppress the response to skin allergy tests, a washout period (from 3 days) is necessary before performing them.
Itching may occur when levocetirizine is discontinued, even if these symptoms were not present before treatment. Itching may disappear on its own. In some cases, itching may be intense, which may be a reason for resuming treatment. After re-administration of levocetirizine, itching usually disappears.
Excipients.
The drug contains the dye sunset yellow FCF (E 110), which may cause allergic reactions.
Use during pregnancy or breastfeeding
Pregnancy
Levocetirizine is contraindicated for use during pregnancy.
Breast-feeding
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.
The ability to influence the reaction speed when driving or working with other mechanisms
You should refrain from driving or operating other potentially dangerous machinery during treatment with the drug.
Method of administration and doses
The drug is prescribed to adults and children over 6 years of age orally in a daily dose of 5 mg once a day, regardless of meals. The tablet should be swallowed whole, washed down with a small amount of water.
Elderly patients with normal renal function: dose adjustment of the drug is not required.
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, the patient's creatinine clearance (CLcr) in mL/min must be estimated. CLcr (mL/min) must be estimated from serum creatinine (mg/dL) using the following formula:
CLcr=[140 – age (years)] x body weight (kg) (x 0.85 for women)/72 x serum creatinine (mg/dL)
Table 1. Dose adjustment for patients with impaired renal function:
| Kidney function | Creatinine clearance, ml/min | Daily dose | Number of receptions |
| Normal kidney function | ≥ 80 | 5 mg (10 ml) | 1 time per day |
| Mild impairment | 50-79 | 5 mg (10 ml) | 1 time per day |
| Moderate impairment | 30-49 | 5 mg (10 ml) | 1 time in 2 days |
| Severe violation | < 30 | 5 mg (10 ml) | 1 time in 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 exclusively hepatic insufficiency. Patients with hepatic and renal insufficiency should adjust the dosage according to the table above.
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 history: treatment can be stopped if the symptoms disappear and can be resumed if the 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 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 using the racemate).
Children
The drug should be used in children over 6 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 not effective in 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 and angioedema.
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: persistent drug eruptions, itching, rash, urticaria.
Musculoskeletal system: myalgia, arthralgia.
Research results: weight gain, abnormal liver function tests.
Nutrition and metabolism disorders: increased appetite.
General disorders and administration site conditions: edema.
Expiration date
3 years.
Storage conditions
Store at a temperature not exceeding 25 ºС.
Keep out of reach of children.
Packaging
10 tablets in a blister; 1 or 3 or 10 blisters in a cardboard box.
Vacation category
Without a prescription.
Producer
KUSUM HEALTHCARE PVT LTD/KUSUM HEALTHCARE PVT LTD.
