Composition, form of production and packaging
? The tablets covered with a film cover of white or almost white color, oblong, biconcave, with engraving "e" on one side.
1 tab.
levocetirizine dihydrochloride 5 mg
Excipients: lactose monohydrate - 67.5 mg, microcrystalline cellulose - 25 mg, sodium carboxymethyl starch - 1 mg, silicon dioxide colloid - 0.5 mg, magnesium stearate - 1 mg.
Composition of the film membrane: hypromellose 2910/5 - 3.3 mg, macrogol 6000 - 0.35 mg, talc - 0.85 mg, titanium dioxide (E171) - 0.5 mg.
7 pcs. - blisters (1) - packs of cardboard.
7 pcs. - blisters (4) - packs of cardboard.
10 pieces. - blisters (2) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2016.
PHARMACHOLOGIC EFFECT
Levocetirizine, (R) -enantiomer of cetirizine, is an inhibitor of peripheral H 1 -gistamine receptors, whose affinity is 2 times higher than that of cetirizine. After a single administration of levocetirizine, H 1 -gistamine receptor binding was observed to be 90% after 4 hours and 57% at 24 hours.
Has an effect on the histamine-dependent stage of allergic reactions; reduces the migration of eosinophils, reduces vascular permeability, limits the release of inflammatory mediators. Prevents development and facilitates the course of allergic reactions, has antiexudative, antipruritic effect; practically does not have anticholinergic and antiserotonin action. In therapeutic doses, it practically does not have a sedative effect. The action begins 12 minutes after a single dose in 50% of patients, after 1 hour in 95% of patients and lasts for 24 hours. Does not affect the QT interval on the ECG.
PHARMACOKINETICS
Pharmacokinetics is linear in nature, independent of dose and time, and varies slightly between people.
Suction
After ingestion, levocetirizine is rapidly and completely absorbed from the digestive tract. Eating does not affect the completeness of absorption, although its rate decreases, C max in plasma is achieved after 0.9 h (54 min) after taking the drug. C max in the plasma after a single dose of levocetirizine at a dose of 5 mg is 270 ng / ml, and after repeated administration at a dose of 5 mg - 308 ng / ml.
Distribution
The binding of levocetirizine to plasma proteins is 90%. V d is 0.4 l / kg. C ss is set after 2 days.
Data on the distribution of levocetirizine in tissues and its penetration through the BBB in humans are absent. Levocetirizine excreted in breast milk.
Metabolism
Levocetirizine is metabolized in small amounts (<14%) in the body by N- and O-dealkylation (unlike other histamine H 1 -receptor antagonists that are metabolized with the participation of CYP isoenzymes) to form a pharmacologically inactive metabolite.
Due to limited metabolism and the absence of metabolic inhibitory activity, the interaction of levocetirizine at the metabolic level with other substances is unlikely.
Excretion
T 1/2 in adults is 7.9 В± 1.9 hours. The average observed total clearance is 0.63 ml / min / kg. Levocetirizine is mainly excreted in the urine, on average, about 85.4% of the dose taken by glomerular filtration and active tubular secretion. Excretion through the intestine (with feces) is only 12.9% of the dose taken.
Pharmacokinetics in special clinical cases
T 1/2 in young children is shorter than in adults.
The total clearance of levocetirizine depends on QC. Therefore, patients with moderate and severe renal insufficiency are encouraged to increase the intervals between doses of the drug in accordance with QC. In patients with anuria and terminal stage of renal failure, the total clearance of levocetirizine is reduced by approximately 80% compared to healthy people. The amount of levocetirizine withdrawn with a standard 4-hour hemodialysis procedure is less than 10%.
INDICATIONS
- Treatment of symptoms of year-round (persistent) and seasonal (intermittent) allergic rhinitis and allergic conjunctivitis, such as itching, sneezing, nasal congestion, rhinorrhea, lacrimation, congestion hyperemia;
- Pollinosis (hay fever);
- urticaria, incl. chronic idiopathic urticaria;
- Quincke's edema (as an auxiliary therapy);
- other allergic dermatoses, accompanied by itching and rashes.
DOSING MODE
The tablet should be taken orally, without liquid and squeezed liquid, regardless of food intake. It is recommended to take a daily dose at one time. Adults, adolescents and children over 6 years of age The recommended daily dose is 5 mg (1 tablet).
Elderly patients
In elderly patients with moderate and severe renal failure, dose adjustment is recommended (see "Patients with impaired renal function" below).
Patients with impaired renal function
The interval between doses of the drug is determined individually, taking into account the function of the kidneys. Information on dose adjustment is given in the table below. To use it, calculate the CK (ml / min) based on the serum creatinine concentration (mg / dL)
CK for men can be calculated based on the serum creatinine concentration, according to the following formula:
KK (ml / min) = [140 - age (years)]? Body weight (kg) / 72? KK serum, (mg / dl)
KK for women can be calculated by multiplying the obtained value by a factor of 0.85.
Correction of dose in patients with impaired renal function
Group CK (ml / min) Dose and frequency of admission
Normal function> 80 5 mg 1 time / day
Easy CRF 50-79 5 mg 1 time / day
Moderate CRF 30-49 5 mg once every 2 days
Severe CRF <30 5 mg once every 3 days
Terminal CRF - patients on dialysis <10 Contraindicated
In children with impaired renal function, the dose is adjusted individually, taking into account CC and body weight. There are no separate data on the use in children with impaired renal function.
With an isolated violation of liver function, dose adjustment is not required. In patients with hepatic renal failure , dose adjustment is recommended.
Duration of treatment
Treatment of allergic rhinitis is carried out in accordance with the course of the disease; The drug can be stopped if symptoms disappear and resume when relapsed. In the case of chronic allergic rhinitis, prolonged treatment during the period of action of allergens can be prescribed. Currently, the clinical experience of the use of levocetirizine in the form of tablets coated with a film coat, 5 mg is limited to 6 months.
SIDE EFFECT
Determination of the frequency of adverse reactions (according to MedDRA): very often (? 1/10), often (? 1/100, <1/10), infrequently (? 1/1000, <1/100), rarely (? 1 / 10 000, <1/1000), very rarely (<1/10 000), the frequency is unknown (according to available data, it is not possible to determine the frequency of occurrence of the side effect).
From the side of the immune system: very rarely - hypersensitivity reactions, incl. anaphylactic reactions.
From the nervous system: often - headache; infrequently - drowsiness; very rarely - aggression, agitation, hallucinations, depression, convulsions.
From the side of the organ of vision: very rarely - visual disorders.
From the cardiovascular system: very rarely - a feeling of palpitations, tachycardia.
From the respiratory system: very rarely - shortness of breath.
From the side of the digestive system: often - dryness of the oral mucosa; infrequently - pain in the abdomen; very rarely - nausea, diarrhea, hepatitis.
From the skin and subcutaneous tissues: very rarely - itching, rash.
Allergic reactions: very rarely - angioedema, drug rash, urticaria.
From the musculoskeletal system: very rarely - myalgia.
General reactions: often fatigue; infrequently, asthenia.
On the part of laboratory indicators: very rarely - a violation of liver function indicators, weight gain.
CONTRAINDICATIONS
- hypersensitivity to levocetirizine and other piperazine derivatives or to any of the auxiliary components of the drug;
- hypersensitivity to other piperazine derivatives;
- terminal renal failure with QC less than 10 ml / min;
- Pregnancy;
- Children under 6 years of age (for this dosage form);
- Congenital intolerance of galactose, deficiency of lactase or malabsorption of glucose-galactose (due to the content of lactose in the preparation).
Carefully:
- chronic renal failure with QC more than 10 ml / min, but less than 50 ml / min (dosage adjustment is required);
- Old age (glomerular filtration may be reduced);
- care must be taken when taking with alcohol at the same time.
PREGNANCY AND LACTATION
The use of the drug during pregnancy is contraindicated.
Levocetirizine is excreted in breast milk, so if it is necessary to use the drug during lactation, breastfeeding should be discontinued.
APPLICATION FOR FUNCTIONS OF THE LIVER
The interval between doses of the drug is determined individually, taking into account the function of the kidneys. Information on dose adjustment is given in the table.
In children with impaired renal function, the dose is adjusted individually, taking into account the clearance of creatinine and body weight. There are no separate data on the use in children with impaired renal function.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
With an isolated violation of liver function, dose adjustment is not required. In patients with hepatic renal failure, dose adjustment is recommended (see "Patients with impaired renal function" above).
APPLICATION FOR CHILDREN
Contraindicated in children under 6 years.
APPLICATION IN ELDERLY PATIENTS
In elderly patients with moderate and severe renal failure, dose adjustment is recommended (see "Patients with impaired renal function" below).
SPECIAL INSTRUCTIONS
During treatment with the drug is not recommended to take ethanol.
Impact on the ability to drive vehicles and manage mechanisms
Levocetirizine, when administered at the recommended doses, does not adversely affect the attention and speed of psychomotor reactions and the ability to drive vehicles. However, during the period of taking the drug, it is advisable to refrain from engaging in potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.
OVERDOSE
Symptoms: drowsiness in adults and excitement, as well as anxiety, followed by drowsiness, in children.
Treatment: there are no specific antidotes of levocetirizine. In case of an overdose, symptomatic or supportive treatment is recommended. If you take a little time after taking the medication, you should wash the stomach. Levocetirizine is practically not excreted in hemodialysis.
DRUG INTERACTION
The interaction of levocetirizine with other drugs, including studies with inducers of the isoenzyme CYP3A4, has not been studied.
When studying the drug interaction of the racemate cetirizine with pseudoephedrine, cimetidine, ketoconazole, erythromycin, azithromycin, glipizide and diazepam, no clinically significant undesirable interaction was detected.
With a simultaneous appointment with theophylline (400 mg / day), the total clearance of cetirizine is reduced by 16% (theophylline kinetics does not change).
In the study, while taking ritonavir (600 mg 2 times / day) and cetirizine (10 mg / day), it was shown that the exposure of cetirizine increased by 40%, and the exposure of ritonavir slightly changed (-11%).
In sensitive patients, concomitant administration of levocetirizine and alcohol or other substances depressing the CNS can exacerbate the effect on the central nervous system, although it has been shown that the racemate of cetirizine does not enhance the effect of alcohol.
TERMS OF RELEASE FROM PHARMACY
The drug is approved for use as a means of OTC.
RU.CTR.15.09.82
TERMS AND CONDITIONS OF STORAGE
The drug should be stored out of the reach of children, at a temperature of no higher than 25 В° C. Shelf life - 2 years.
