Instructions for use L-cet syrup 2.5 mg/5 ml bottle 100 ml
Composition
active ingredient: levocetirizine dihydrochloride;
5 ml of syrup contains levocetirizine dihydrochloride 2.5 mg;
excipients: glycerin, propylene glycol, sodium methyl parahydroxybenzoate (E 219), sodium propyl parahydroxybenzoate (E 217), sucrose, glacial acetic acid, sodium acetate trihydrate, peppermint flavor, banana flavor, purified water.
Dosage form
Syrup.
Main physicochemical properties: colorless transparent viscous liquid with a characteristic odor.
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 antagonists of peripheral H1-histamine receptors. The pharmacological action is due to the blockade of H1-histamine receptors. In binding studies, levocetirizine was found to have a high affinity for human H1-receptors (Ki = 3.2 nmol/l). The affinity of levocetirizine is twice that of cetirizine (Ki = 6.3 nmol/l). Levocetirizine dissociates from H1-receptors with a half-life of 115±38 min. After a single dose, the binding of levocetirizine to the receptors was 90% after 4 hours and 57% after 24 hours. Pharmacodynamic studies in healthy volunteers have shown that half the dose of levocetirizine has comparable activity to cetirizine in both skin and nasal manifestations.
Pharmacokinetics.
The pharmacokinetics 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 elimination.
Absorption. Levocetirizine is rapidly and extensively absorbed after oral administration. The maximum concentration in the blood plasma is reached 0.9 h after administration. Steady state is reached after 2 days. The maximum concentration (Cmax) is usually 270 ng/ml and 308 ng/ml, respectively, after single and multiple administration of the drug at a dose of 5 mg 1 time / day. The extent of absorption does not depend on the dose. The extent of absorption does not change with food intake, but the maximum concentration (Cmax) of the drug decreases and is reached later.
Distribution. There are no data on the distribution of the drug in human tissues, as well as data on the passage 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 dose, and therefore differences due to genetic polymorphism or concomitant use of hepatic enzyme inhibitors are 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 does 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.
Excretion. The drug is excreted in two ways: 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. 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 is excreted in the feces.
Special populations
Kidney dysfunction.
The apparent total 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 based on 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%.
A comparative cross-over study of a single oral dose of 5 mg levocetirizine showed that Cmax and AUC values in 14 children aged 6 to 11 years with a body weight of 20 to 40 kg were approximately 2-fold higher than those obtained in healthy adult subjects. The mean weight-normalized Cmax, which was reached on average in 1.2 hours, was 450 ng/ml, the total clearance was 30% higher, and the half-life was 24% shorter in the pediatric population than in adults. Specific pharmacokinetic studies in children under 6 years of age have not been conducted. A retrospective population pharmacokinetic analysis was conducted in 323 patients (181 children aged 1 to 5 years, 18 children aged 6 to 11 years and 124 adults aged 18 to 55 years) who received single or multiple doses of levocetirizine ranging from 1.25 mg to 30 mg. The data obtained from this analysis showed that administration of 1.25 mg of levocetirizine once daily in children aged 6 months to 5 years would be expected to result in plasma concentrations similar to those in adults receiving 5 mg of levocetirizine once daily.
Elderly patients.
Pharmacokinetic data in elderly patients are limited. After repeated oral administration of 30 mg levocetirizine once daily for 6 days in 9 elderly subjects (aged 65–74 years), total clearance was approximately 33% lower than in younger adults. The distribution of racemic cetirizine has been shown to be dependent on renal function, not age. This conclusion is also applicable to levocetirizine, since both levocetirizine and cetirizine are predominantly excreted in the urine. Therefore, the dose of levocetirizine should be adjusted in elderly patients according to renal function.
Sex
Pharmacokinetic results for 77 patients (40 males and 37 females) were evaluated for potential effects of gender. The elimination half-life was slightly shorter in females (7.08 ± 1.72 hours) than in males (8.62 ± 1.84 hours); however, the weight-adjusted oral clearance in females (0.67 ± 0.16 mL/min/kg) was comparable to that in males (0.59 ± 0.12 mL/min/kg). The same daily doses and dosing intervals can be used for males and females with normal renal function.
Race
The effect of race on levocetirizine has not been studied. Since levocetirizine is primarily excreted by the kidneys and there are no significant racial differences in creatinine clearance, the pharmacokinetics of levocetirizine are not expected to differ based on race. No racial differences were observed in the kinetics of racemic cetirizine.
Liver dysfunction
The pharmacokinetics of levocetirizine in patients with hepatic impairment have not been studied. In patients with chronic liver disease (hepatocellular, cholestatic and biliary cirrhosis) given a single dose of 10 or 20 mg of racemic cetirizine, a 50% increase in half-life was observed, together with a 40% decrease in clearance compared to healthy subjects.
Indication
Symptomatic treatment of allergic rhinitis (including perennial allergic rhinitis) and urticaria in adults and children aged 2 years and older.
Contraindication
Hypersensitivity to levocetirizine, cetirizine, hydroxyzine or any other piperazine derivatives, as well as to any other excipient of the medicinal product.
Severe chronic renal failure (creatinine clearance < 15 ml/min) (requiring dialysis).
Interaction with other medicinal products and other types of interactions
Interaction studies with levocetirizine have not been conducted (including studies of interactions with CYP3A4 inducers); studies of the racemate cetirizine have shown no clinically significant adverse interactions (with antipyrine, azithromycin, cimetidine, diazepam, erythromycin, glipizide, ketoconazole, and pseudoephedrine). A slight decrease in cetirizine clearance (16%) was observed in a multiple-dose study with concomitant theophylline (400 mg once daily); the disposition of theophylline was not altered by concomitant cetirizine administration.
In a study of multiple doses of ritonavir (600 mg twice daily) and cetirizine (10 mg daily), cetirizine exposure increased by 40%, while ritonavir exposure changed little (-11%).
The extent of absorption of levocetirizine is not reduced by food, although the rate of absorption is reduced.
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
During treatment with levocetirizine, alcohol consumption should be avoided (see section “Interaction with other medicinal products and other types of interactions”).
When prescribing the drug to patients with factors contributing to urinary retention (e.g. spinal cord injuries, prostatic hyperplasia), it should be taken into account that levocetirizine increases the risk of urinary retention.
Antihistamine medications suppress the response to skin allergy testing, so before performing it, the medication must be stopped 3 days before it is performed (withdrawal period).
Itching may occur after discontinuation of levocetirizine, even if these symptoms were not present before treatment. These symptoms may disappear on their own. In some cases, the severity of the symptoms may be significant, requiring resumption of the drug. After resumption of treatment, the symptoms should disappear.
Pediatric population
The availability of some clinical data on the use of levocetirizine in children aged 6 months to 12 years is not sufficient to justify its use in infants and children under 2 years of age.
Excipients.
The medicine contains sucrose, so if you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.
The drug contains sodium methyl parahydroxybenzoate and sodium propyl parahydroxybenzoate, which may cause allergic reactions (possibly delayed).
Use during pregnancy or breastfeeding
Pregnancy.
There are no or limited amount of data (less than 300 pregnancy outcomes) on the use of levocetirizine in pregnant women. However, for cetirizine, the racemate of levocetirizine, a large amount of data (more than 1000 pregnancy outcomes) on pregnant women indicate no malformative or feto/neonatal toxicity. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development.
If necessary, the use of levocetirizine during pregnancy may be considered.
Breast-feeding.
Cetirizine, the racemate of levocetirizine, has been shown to be excreted in human milk. Therefore, it is possible that levocetirizine may be excreted in breast milk. Adverse reactions associated with levocetirizine may occur in breastfed infants. Therefore, caution should be exercised when levocetirizine is administered to breastfeeding women.
Fertility
There are no clinical data on the effect of levocetirizine on fertility.
Ability to influence reaction speed when driving vehicles or other mechanisms
Comparative clinical trials 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 treatment with levocetirizine. Therefore, patients who intend to drive vehicles, engage in potentially hazardous activities or operate machinery should take into account their reaction to the drug.
Method of administration and doses
The drug should be administered orally to adults and children aged 2 years and older, regardless of meals.
Dosage
Adults and children aged 12 and over.
The daily dose is 5 mg (10 ml of syrup) once a day.
Elderly patients.
Dose adjustment is recommended for elderly patients with moderate to severe renal impairment (see Renal impairment section).
Kidney failure.
Dosage intervals should be individualized based on renal function (eGFR - estimated glomerular filtration rate). Refer to the table and adjust the dose as indicated.
Table. Dosage adjustment for patients with impaired renal function.
| Group | eGFR, ml/min | Dosage and number of doses |
| Normal kidney function | ≥ 90 | 5 mg (10 ml syrup) once a day |
| Mild impairment | 60 – <90 | 5 mg (10 ml syrup) once a day |
| Moderate impairment | 30 – <60 | 5mg (10 ml syrup) once every 3 days |
| A sharp decline in kidney function | 15 – <30 (do not require dialysis) | 5mg (10 ml syrup) once every 3 days |
| End-stage renal failure | <15 (needs dialysis treatment) | 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 exclusively hepatic impairment. For patients with hepatic and renal impairment, dosage adjustment is required according to the table above.
Children
Children aged 6 to 12 years: the recommended daily dose is 5 mg (10 ml of syrup) once a day.
Children aged 2 to 6 years: the recommended daily dose is 2.5 mg divided into 2 doses of 1.25 mg (2.5 ml of syrup 2 times a day).
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 with cetirizine (racemate)).
Children.
Use 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 in adults may include drowsiness. In children, agitation and 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 should be considered shortly after ingestion. Hemodialysis is not effective in removing levocetirizine from the body.
Side effects
Clinical trials
Adults and adolescents over 12 years of age.
In therapeutic trials involving women and men aged 12 to 71 years, 15.1% of patients in the levocetirizine 5 mg group experienced at least one adverse reaction compared to 11.3% in the placebo group. 91.6% of these adverse reactions were mild to moderate in severity.
In therapeutic trials, the incidence of withdrawal due to adverse events was 1.0% (9/935) with levocetirizine 5 mg and 1.8% (14/771) with placebo.
Clinical therapeutic trials of levocetirizine included 935 patients receiving the recommended dose of 5 mg daily. From this population, the following adverse reactions were reported with an incidence of 1% or more (common: ≥1/100 to <1/10) with levocetirizine 5 mg or placebo:
| Adverse reaction | Placebo (n=771) | Levocetirizine 5 mg (n = 935) |
| headache | 25 (3.2%) | 24 (2.6%) |
| drowsiness | 11 (1.4%) | 49 (5.2%) |
| dry mouth | 12 (1.6%) | 24 (2.6%) |
| increased fatigue | 9 (1.2%) | 23 (2.5%) |
Asthenia and abdominal pain have also been reported uncommonly (≥ 1/1000, < 1/100).
The incidence of sedative adverse reactions such as somnolence, fatigue and asthenia was generally higher (8.1%) with levocetirizine 5 mg than with placebo (3.1%).
Children
In two placebo-controlled studies in pediatric patients aged 6 to 11 months and 1 to 6 years, 159 subjects received levocetirizine at a dose of 1.25 mg daily for 2 weeks and 1.25 mg twice daily, respectively. The incidence of adverse reactions was 1% or greater with levocetirizine or placebo.
| Organ systems and adverse reactions | Placebo (n=83) | Levocetirizine (n=159) |
| from the digestive tract | | |
| diarrhea | 0 | 3(1.9%) |
| vomiting | 1(1.2%) | 1(0.6%) |
| constipation | 0 | 2(1.3%) |
| from the nervous system | | |
| drowsiness | 2(2.4%) | 3(1.9%) |
| from the psyche | | |
| sleep disturbance | 0 | 2(1.3%) |
In children aged 6 to 12 years, double-blind, placebo-controlled studies were conducted in which 243 children received 5 mg levocetirizine daily for periods ranging from less than 1 week to 13 weeks. The following adverse reactions were reported with levocetirizine or placebo at a frequency of 1% or greater.
| Adverse reactions | Placebo (n=240) | Levocetirizine 5mg (n=243) |
| headache | 5(2.1%) | 2(0.8%) |
| drowsiness | 1(0.4%) | 7(2.9%) |
Post-marketing experience
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.
From the side of the organs of hearing and balance: frequency unknown: vertigo.
On the part of the organs of vision: frequency unknown: visual impairment, blurred vision, oculogyration.
Cardiac disorders: frequency unknown: palpitations, tachycardia.
Gastrointestinal: frequency unknown: diarrhea, vomiting, constipation, dry mouth, nausea, abdominal pain.
Hepatobiliary disorders: frequency unknown: hepatitis.
Renal and urinary disorders: frequency unknown: dysuria, urinary retention.
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 of suspected adverse reactions.
Reporting adverse reactions after the registration of a medicinal product is important. This allows monitoring of the benefit/risk ratio of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all cases of suspected adverse reactions and lack of efficacy of the medicinal product via the Automated Information System for Pharmacovigilance at the following link: https://aisf.dec.gov.ua
Expiration date
3 years.
Storage conditions
Store at a temperature not exceeding 25 °C in the original packaging.
Keep out of reach of children.
After first opening the bottle, store the drug for no more than 4 weeks.
Packaging
60 ml or 100 ml in polyethylene or glass bottles. Each bottle is packed in a cardboard box with a measuring spoon.
Vacation category
Without a prescription.
Producer
"KUSUM FARM" LLC.
Address
40020, Ukraine, Sumy region, Sumy city, Skryabina st., 54.
