Tsetrilev

Cetrilev is an antihistamine systemic drug, the active substance of which is levocetirizine, an active stable R-enantiomer of cetirizine, a piperazine derivative.

Indications Tsetrileva

It is used to eliminate the symptoms of allergic rhinitis (also a year-round form of the disease), as well as urticaria.

Release form

Available in 5 mg tablets, 10 tablets per blister. A pack contains 1 blister plate; in the form of syrup in 30, 50 or 100 ml bottles. Inside the package there is 1 bottle complete with a measuring cap.

Pharmacodynamics

Levocetirizine is an active R-enantiomer of the substance cetirizine with stable properties. A component of the group of competitive histamine antagonists. Its medicinal properties are determined by blocking the endings of H1 histamine. The affinity for these elements in levocetirizine is twice as high as that of cetirizine.

It affects the histamine-dependent stage of development of allergy manifestations, reduces vascular permeability, the activity of eosinophil movement, and also limits the process of release of inflammatory conductors. It prevents the appearance of an allergic response, and, together with this, alleviates the course of already existing symptoms. The component also has anti-inflammatory, anti-allergic and anti-exudative properties, while having almost no anti-serotonin and cholinolytic effect.

When taken in medicinal doses, it has virtually no sedative effect.

Pharmacokinetics

The pharmacokinetics of levocetirizine are linear and are virtually identical to those of cetirizine.

When taken orally, the drug is absorbed intensively and quickly. The degree of absorption does not change depending on food intake and the size of the dose taken, although a decrease in peak concentration and an extension of the time to reach it are observed. The bioavailability level is 100%.

In 5% of patients, the drug effect begins 12 minutes after a single dose, and in the remaining 95% - after 0.5-1 hour. The peak plasma level is observed 50 minutes after a single oral dose of the drug, and its duration is 2 days. The peak indicator is 270 ng / ml with a single dose, and 308 ng / ml in the case of repeated administration of 5 mg of the drug.

There is no information on the distribution of the drug within tissues and its passage through the BBB. Tests have shown that the highest concentration is observed in the kidneys and liver, and the lowest - inside the tissues of the central nervous system. The distribution volume is 0.4 l / kg. Synthesis of the substance with plasma protein is 90%.

Approximately 14% of levocetirizine is metabolized within the body. During this process, a combination with taurine, oxidation, and N- and O-dealkylation occur. The latter are carried out with the help of the hemoprotein CYP 3A4, while oxidative processes are assisted by numerous or unknown isoforms of the CYP element.

Levocetirizine does not affect the activity of hemoprotein isoenzymes 1A2 with 2C9, as well as 2C19 and 2D6 together with 2E1 and 3A4 at values that are several times higher than the maximum level with oral administration of 5 mg of the drug. Since the metabolism is quite low, and the ability to suppress this process is absent, the probability of interaction between levocetirizine and other medicinal components is extremely low.

The excretion of the substance is mainly performed by glomerular filtration and active tubular secretion. The half-life from plasma (adults) is 7.9+1.9 hours. In children, this period is shorter. The total clearance rate (adults) is 0.63 ml/minute/kg. The excretion of the active ingredient and decay products occurs mainly with urine (average rate is 85.4% of the dose consumed). Only 12.9% of the substance is excreted with feces.

The apparent clearance rate of levocetirizine in the body is correlated with the CC index. Because of this, people with severe or moderate renal impairment need to adjust the intervals between levocetirizine intakes, taking into account the CC index. In the presence of anuria at the final stage of end-stage renal disease, the overall clearance level in such people, compared with similar indicators in people without such disorders, decreases by approximately 80%.

The amount of active substance removed by hemodialysis (a standard procedure lasting 4 hours) is <10%.

Dosing and administration

The syrup should be taken orally (children from six months and adults) regardless of food intake. The following dose sizes are recommended:

• infants 0.5-1 year old – once a day, 1.25 mg (or 2.5 ml);
• age 1-2 years – twice a day, 1.25 mg (the daily dose will be 2.5 mg);
• ages 2-6 years – take 1.25 mg (or 2.5 ml) of the medicine twice a day;
• age 6-12 years – 5 mg (or 10 ml) of the drug per day;
• teenagers from 12 years of age, and also adults – once a day, 5 mg (or 10 ml) of syrup.

People with kidney problems need to calculate dosages according to the CC values. The calculation is as follows:

• with normal renal function (creatinine clearance level ≥80 ml/minute) – 5 mg once a day;
• for mild disorders (creatinine clearance rate 50-79 ml/minute) – a single dose of 5 mg of the drug;
• moderate disorders (creatinine clearance level 30-49 ml/minute) – take 5 mg once every other day;
• severe disorder (CC level <30 ml/minute) – taking 5 mg syrup once every 3 days;
• end-stage renal pathology (creatinine clearance level <10 ml/minute) and persons undergoing dialysis – taking the drug is prohibited.

The duration of taking the syrup for people with periodic allergic rhinitis (signs of the disease appear in a period of <4 days per week or in a period of less than 1 month) is determined taking into account the anamnesis and the course of the pathology. Therapy can be stopped when symptoms disappear and resumed if the allergy starts again.

In case of persistent allergic rhinitis (signs of the disease appear for >4 days per week or for a period longer than 1 month) during constant contact with allergens, permanent treatment is possible.

To eliminate chronic pathologies (urticaria or allergic rhinitis), a course of up to 1 year may be required (this information was obtained through tests using the racemate).

The tablets should be taken orally with water and without chewing. If taken on an empty stomach, the onset of medicinal action is faster.

The daily dose for children aged 6 years and over and adults is 5 mg once a day (1 tablet). When treating hay fever, the course lasts on average 1-6 weeks. To eliminate chronic allergic diseases, a course of up to 1 year may be required.

Use Tsetrileva during pregnancy

Levocetirizine should not be prescribed to pregnant women.

Since cetirizine can penetrate into breast milk, if there is a need to use Cetrilev, it is necessary to stop breastfeeding during treatment.

Contraindications

Main contraindications:

• intolerance to levocetirizine or other components of the drug, as well as various derivatives of piperazine;
• chronic severe renal failure (creatinine clearance level is <10 ml/minute);
• It is prohibited to prescribe levocetirizine to newborns and children under six months of age, since information on the use of the drug at this age is very limited;
• The tablets should not be taken by children under 6 years of age.

Side effects Tsetrileva

The components of the syrup methylparaben with propyl parahydroxybenzoate can cause the following side effects (may have a delayed reaction):

• manifestations from the nervous system: a feeling of weakness, drowsiness, severe fatigue, the appearance of headaches, fainting, convulsions, tremors, paresthesia and dizziness, as well as the development of dysgeusia or asthenia;
• mental disorders: feelings of agitation, aggression, hallucinations, thoughts of suicide, depression, insomnia and other sleep disorders;
• heart reactions: development of tachycardia or increased heart rate;
• visual organs: blurred vision and other disorders;
• auditory disorders: development of vertigo;
• bile ducts and liver: development of hepatitis;
• urinary organs and kidneys: urinary retention and the appearance of dysuria;
• immune reactions: manifestations of hypersensitivity, including anaphylaxis;
• organs of the respiratory system, mediastinum and sternum: occurrence of dyspnea;
• gastrointestinal reactions: constipation, nausea, diarrhea, vomiting, abdominal pain and dry mouth;
• subcutaneous layers and skin: the appearance of persistent drug rash, other rashes and itching, as well as the development of urticaria or Quincke's edema;
• muscle structure and bones: occurrence of myalgia;
• laboratory test results: weight gain, changes in normal liver function tests;
• metabolic disorders: increased appetite;
• systemic disorders: the appearance of edema.

Overdose

An overdose is manifested by a feeling of drowsiness, but in children this symptom is preceded by increased irritability and agitation.

Levocetirizine has no specific antidote. If disorders develop, it is necessary to provide the victim with assistance aimed at maintaining the condition and eliminating symptoms. Gastric lavage is possible if the drug was taken recently. Hemodialysis will not give results.

Interactions with other drugs

Interaction tests for levocetirizine have not been performed.

Interaction tests of cetirizine (in combination with the racemate) have shown that combination with cimetidine, antipyrine, as well as ketoconazole and pseudoephedrine, as well as azithromycin, erythromycin and glipizide or diazepam does not cause drug-significant side effects.

When combined with theophylline (daily dose 400 mg), the total clearance of levocetirizine decreases (by 16%), while the properties of theophylline remain unchanged.

Testing of multiple doses of ritonavir (600 mg twice daily) with cetirizine (10 mg daily) demonstrated that cetirizine exposure was increased by approximately 40%, while ritonavir volume of distribution was slightly altered (-11%) prior to combination with cetirizine.

Food does not affect the degree of absorption of the drug, but it does slow it down.

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Storage conditions

Cetrilev must be stored out of the reach of small children, at a temperature not exceeding 30°C.

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Shelf life

Cetrilev (in the form of syrup and tablets) is suitable for use during the period of 24 months from the date of manufacture of the medicine. At the same time, after opening the bottle with syrup, the shelf life of the medicine is 3 months.