Zirtek - instructions for use, dose, side effects, contraindications

Excipients: cellulose microcrystalline 37.00 mg, lactose monohydrate 66.40 mg, silicon dioxide colloid 0.60 mg, magnesium stearate 1.25 mg, opadrai^® Y-1-7000 3.45 mg (hypromellose (E 464) 2.156 mg, titanium dioxide (E 171) 1.078 mg, macrogol 400 0.216 mg).

Description:

White oblong film-coated tablets with biconvex surfaces, with one-sided risk and engraving "Y"on both sides of the risks.

Pharmacotherapeutic group:Antiallergic agent H1-histamine receptor blocker

ATX: & nbsp

E.06.A.E.07 Cetirizine

Pharmacodynamics:

Cetirizine, the active substance of Zirtek®, is a metabolite of hydroxyzine, belongs to the group of competitive histamine antagonists and blocks H₁-gistaminovye receptors.

In addition to the antihistamine effect cetirizine prevents development and facilitates the course of allergic reactions: at a dose of 10 mg once or twice a day inhibits the late phase of the aggregation of eosinophils in the skin and conjunctiva of patients who have allergic reactions.

Clinical efficacy and safety

Studies in healthy volunteers have shown that cetirizine in doses of 5 or 10 mg significantly inhibits the reaction in the form of rash and redness to the introduction of high concentration of histamine into the skin, however, the correlation with the efficacy is not established.

In a 6-week, placebo-controlled study involving 186 patients with allergic rhinitis and concomitant bronchial asthma in the lung and mild-to-severe course, it was shown that taking cetirizine at a dose of 10 mg once a day reduces the symptoms of rhinitis and does not affect lung function.

The results of this study confirm the safety of cetirizine in patients with allergies and bronchial asthma of the lung and moderate course.

In a placebo-controlled study, it was shown that taking cetirizine at a dose of 60 mg per day for 7 days did not cause clinically significant lengthening of the interval QT.

The intake of cetirizine at the recommended dose showed an improvement in the quality of life of patients with year-round and seasonal allergic rhinitis.

Children

In a 35-day study involving patients aged 5-12 years, no signs of immunity to the antihistamine effect of cetirizine. The normal skin reaction to histamine was restored within three days after discontinuation of the drug with its repeated application.

Pharmacokinetics:

The pharmacokinetic parameters of cetirizine when used in doses ranging from 5 to 60 mg vary linearly.

Suction

The maximum concentration in the blood plasma is achieved after 1 ± 0.5 hours and is 300 ng / ml.

Various pharmacokinetic parameters, such as the maximum concentration in the blood plasma (C_m_Oh) and the area under the curve "concentration-time" (AUC) have a homogeneous character.

Eating does not affect the full absorption of cetirizine, although its rate decreases.

Bioavailability of various dosage forms of cetirizine (solution, capsules, tablets) is comparable.

Distribution

Cetirizine binds to plasma proteins by 93 ± 0.3%. Apparent volume of distribution (V_d) is 0.5 l / kg. Cetirizine does not affect the binding of warfarin with proteins.

Metabolism

Cetirizine is not subjected to extensive primary metabolism

Excretion

Half-life (T_1/2) is approximately 10 hours.

When taking the drug in a daily dose of 10 mg for 10 days cumulation of cetirizine was not observed.

Approximately 2/3 of the accepted dose of the drug is excreted in the urine unchanged.

Elderly patients:

In 16 elderly people with a single dose of 10 mg T_1/2 was higher by 50%, and the clearance was lower by 40% compared with the elderly.

The decrease in cetirizine clearance in elderly patients is probably associated with a decrease in renal function in this category of patients.

Patients with renal insufficiency:

In patients with mild renal insufficiency (creatinine clearance> 40 ml / min), pharmacokinetic parameters are similar to those in healthy volunteers with normal renal function.

In patients with moderate renal insufficiency and in patients on hemodialysis (CC <7 ml / min), when taking the drug inside at a dose of 10 mg T_1/2 lengthens 3-fold, and the total clearance is reduced by 70% relative to healthy volunteers with normal renal function.

For patients with moderate or severe renal failure, an appropriate change in the dosing regimen is required. Cetirizine practically not removed from the body during hemodialysis.

Patients with hepatic insufficiency:

In patients with chronic liver disease (hepatocellular, cholestatic and biliary cirrhosis) with a single dose of 10 or 20 mg T_1/2 increases by about 50%, and the clearance decreases by 40% compared with healthy subjects. Correction of the dose is necessary only if the patient with hepatic insufficiency also has concomitant renal failure.

Children:

T_1/2in children from 6 to 12 years is 6 hours, from 2 to 6 years - 5 hours, from 6 months to 2 years - reduced to 3.1 hours.

Indications:

Cetirizine dihydrochloride, 10 mg film-coated tablets is indicated for use in adults and children 6 years and older for relief:

- nasal and ocular symptoms of year-round (persistent) and seasonal (intermittent) allergic rhinitis and allergic conjunctivitis: pruritus, sneezing, nasal congestion, rhinorrhea, lacrimation, conjunctival hyperemia;

- symptoms of chronic idiopathic urticaria.

Contraindications:

- hypersensitivity to cetirizine, hydroxyzine or piperazine derivative, as well as other components of the drug;

- terminal stage of renal failure (creatinine clearance <10 ml / min);

- Children under 6 years of age (for this dosage form);

- Pregnancy;

- Hereditary intolerance to galactose, a lack of lactase or a syndrome of glucose-galactose malabsorption.

Carefully:

- chronic renal failure (with a clearance of creatinine> 10 ml per minute, correction of the dosing regimen is required);

- patients of advanced age (with an age-related decrease in glomerular filtration);

- epilepsy and patients with increased convulsive readiness;

- patients with predisposing factors to urinary retention (see section "Special instructions");

- the period of breastfeeding.

Pregnancy and lactation:

Pregnancy

When analyzing the prospective data of more than 700 cases of pregnancy outcomes, there were no cases of formation of developmental defects, embryonic and neonatal toxicity with a clear cause-and-effect relationship.

Experimental studies in animals have not revealed any direct or indirect adverse effects of cetirizine on the developing fetus (including the postnatal period), the course of pregnancy and childbirth.

Adequate and strictly controlled clinical studies on the safety of the drug during pregnancy was not conducted, so Zirtek® should not be used during pregnancy.

Breast-feeding

Cetirizine excreted in breast milk in a concentration representing 25% to 90% of the concentration of the drug in the blood plasma, depending on the time after the appointment. During the period of breastfeeding, it is used after consultation with the doctor if the intended benefit to the mother exceeds the potential risk to the child.

Fertility

Available data on the impact on human fertility are limited, but there is no adverse effect on fertility.

Dosing and Administration:

Inside. It is recommended to drink tablets with a glass of water.

Adults

10 mg (1 tablet) once a day.

Sometimes an initial dose of 5 mg (1/2 tablet) can be sufficient if this allows you to achieve a satisfactory control of the symptoms.

Elderly patients

There is no need to reduce the dosage in elderly patients if the kidney function is not impaired.

Patients with renal insufficiency

Since Zirtek is excreted from the body mainly by the kidneys (see subsection "Pharmacokinetics"), if alternative treatment is not possible patients with renal insufficiency The dosage regimen should be adjusted depending on the function of the kidneys (the creatinine clearance value of the CC).

The creatinine clearance (CK) for men can be calculated based on the serum creatinine concentration, according to the following formula:

[140 - age (years)] х body weight (kg)

KK (ml / min) = ------------------------------------------- -------------------------

72 х КК_serum (mg / dL)

KK for women can be calculated by multiplying the obtained value by a factor of 0.85.

Dosing in Adults with Renal Failure

Renal insufficiency	CK (ml / min)	Dosing regimen
Norm	>80	10 mg / day
Lightweight	50-79	10 mg / day
Average	30-49	5 mg / day
Heavy	10-29	5 mg every other day
Terminal stage patients on dialysis	< 10	the drug is contraindicated

Patients with impaired hepatic function

In patients with a dysfunction only liver function, correction of the dosing regimen is not required.

In patients with impaired and liver function, and kidney function, correction of dosing is recommended (see table above)

Children

Children from 6 to 12 years old 5 mg (1/2 tablet) twice daily

Children over 12 years old 10 mg (1 tablet) once a day

Sometimes an initial dose of 5 mg (1/2 of a tablet) can be sufficient if this allows for satisfactory symptom control.

Children with renal insufficiency dose adjusted for QA and body weight.

Side effects:

Data, obtained in clinical trials
Overview

The results of clinical studies have demonstrated that the use of cetirizine at recommended doses leads to the development of minor undesirable effects on the CNS, including drowsiness, fatigue, dizziness and headache. In some cases, a paradoxical stimulation of the central nervous system was registered.

Although cetirizine is a selective blocker of peripheral H₁receptors and practically does not render anticholinergic action, there were reports of single cases of difficulty urinating, accommodation disorders and dry mouth. Reported violations of liver function, accompanied by increased levels of hepatic enzymes and bilirubin. In most cases, adverse events were resolved after discontinuing cetirizine dihydrochloride.

The list of undesirable side reactions

There are data from double-blind, controlled clinical trials aimed at comparing cetirizine and placebo or other antihistamines used at the recommended doses (10 mg once daily for cetirizine) in more than 3,200 patients, on the basis of which a reliable analysis can be made safety data.

According to a combined analysis, in placebo-controlled studies with cetirizine at a dose of 10 mg, the following adverse reactions were observed with a frequency of 1.0% or higher

Undesirable reactions (WHO terminology)	Cetirizine 10 mg (n = 3260)	Placebo (n = 3061)
General violations and violations at the site of introduction Fatigability	1,63%	0,95%
Disturbances from the nervous system Dizziness	1,10%	0,98%
Headache	7,42%	8,07%
Disorders from the gastrointestinal tract Abdominal pain	0,98%	1,08%
Dry mouth	2,09%	0,82%
Nausea	1,07%	1,14%
Disorders of the psyche
Drowsiness	9,63%	5,00%
Infringements from
respiratory system, organs
thorax and mediastinum
Pharyngitis	1,29%	1,34%

Although the incidence of sleepiness in the cetirizine group was higher than that in the placebo group, in most cases this adverse event was mild or moderate in severity. In an objective evaluation conducted in other studies, it was confirmed that the use of cetirizine in the recommended daily dose in healthy young volunteers does not affect their daily activity.

Children

In placebo-controlled studies, the following adverse events were observed in children aged 6 months to 12 years at a frequency of 1% or more:

Undesirable reactions (WHO terminology)	Cetirizine (n = 1656)	Placebo (n =1294)
Infringements from gastrointestinal tract Diarrhea	1,0%	0,6%
Disorders of the psyche Drowsiness	1,8%	1,4%
Disturbances from the respiratory system, chest and mediastinal organs Rhinitis	1,4%	1,1%
General violations and violations at the site of introduction Fatigability	1,0%	0,3%

Experience of post-registration application

In addition to the adverse events identified in clinical trials and described above, the following adverse reactions were observed in the post-marketing use of the drug.Adverse events are presented below in terms of organ system classes MedDRA and frequency of development, on the basis of data on the post-marketing use of the drug.

The incidence of adverse events was determined as follows: very often (≥1/10), often (≥1 / 100, <1/10), infrequently (≥1 / 1000, <1/100), rarely (≥1 / 10000, <1/1000), very rarely (<1/10000), the frequency is unknown (due to insufficient data).

From the side of the blood and lymphatic system:

Rarely: thrombocytopenia

From the immune system:

Rarely: hypersensitivity reactions

Rarely: anaphylactic shock

Metabolic and nutritional disorders:

Frequency unknown: increased appetite

Disorders from the psyche:

Infrequently: excitation

Rarely: aggression, confusion, depression, hallucinations, sleep disturbance.

Rarely: teak

Frequency unknown: suicidal ideas

From the nervous system

Infrequently: paresthesia

Rarely: convulsions

Rarely: perversion of taste, dyskinesia, dystonia, syncope, tremor

Frequency unknown: memory impairment, including amnesia

From the side of the organ of vision

Rarely: disruption of accommodation, blurred vision, nystagmus

From the organs of hearing

Frequency unknown: vertigo

From the side of the cardiovascular system

Rarely: tachycardia

From the digestive system

Infrequently: diarrhea

Hepatobiliary disorders

Rarely: change in functional liver samples (increased activity of transaminases, alkaline phosphatase, gamma-glutamyltransferase and bilirubin)

From the skin side

Infrequently: rash, itching

Rarely: hives

Rarely: angioedema, persistent drug erythema

From the urinary system

Rarely: dysuria, enuresis

Frequency unknown: retention of urine

General disorders

Infrequently: asthenia, malaise

Rarely: peripheral edema

Research

Rarely: weight gain

Notification of adverse reactions:

Of great importance is the system of notification of suspected adverse reactions after registration of the drug.

This allows continuous monitoring of the drug benefit / risk ratio.

Overdose:

Symptoms:

With a single dose of 50 mg, the following symptoms: confusion, diarrhea, dizziness, fatigue, headache, malaise,mydriasis, itching, restlessness, weakness, sedation, drowsiness, stupor, tachycardia, tremor, retention of urine.

Treatment: immediately after taking the drug - gastric lavage or stimulation of vomiting. It is recommended to take activated charcoal, conduct symptomatic and maintenance therapy. There is no specific antidote. Hemodialysis is ineffective.

Interaction:

Based on the analysis of pharmacodynamics, pharmacokinetics of cetirizine, interaction with other drugs is unlikely.

There were no significant interactions with pseudoephedrine and theophylline (at a dose of 400 mg per day) in special studies of drug interactions.

Simultaneous use of cetirizine with alcohol and other drugs that depress the central nervous system can further reduce the concentration of attention and rapidity of reactions, although cetirizine does not enhance the effect of alcohol (when its concentration in the blood is 0.5 g / l).

Special instructions:

It is recommended to be cautious when using cetirizine concomitantly with alcohol, although there is no clinically significant interaction with alcohol at therapeutic doses (at a blood alcohol concentration of 0.5 g / l).

In patients with spinal cord injury, prostatic hyperplasia, and other predisposing factors to urinary retention, caution is required, since cetirizine may increase the risk of urinary retention.

Caution should be observed in patients with epilepsy and increased convulsive readiness.

Prior to the appointment of allergological samples, a three-day "washout" period is recommended because H1-histamine receptors blockers inhibit the development of skin allergic reactions.

Cetirizine in film-coated tablets should not be given to patients with hereditary intolerance to galactose, a deficiency of lactase, or a syndrome of glucose-galactose malabsorption.

Children

Cetirizine in film-coated tablets is not recommended for children under 6 years of age, since this dosage form does not allow the use of a suitable dosage for this age group. It is recommended to use a pediatric dosage form (drops for oral administration).

Effect on the ability to drive transp.cf. and fur:

With an objective assessment of the ability to drive vehicles and manage mechanisms, there are no undesirable events when taking the drug at the recommended dose. However, patients with drowsiness on the background of taking the drug is advisable to refrain from driving a car, engaging in potentially dangerous activities or controlling mechanisms that require an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:Film coated tablets 10 mg.

Packaging:

For 7 or 10 tablets in a planar cell package (blister) [PVC / aluminum foil]. For 1 (7 or 10 tablets) or 2 (10 tablets) blister, along with instructions for use in a cardboard pack.

Storage conditions:

At a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:

5 years/

Do not take it after the expiration date.

Terms of leave from pharmacies:Without recipe

Registration number:П N014186 / 01

Date of registration:13.08.2008

The owner of the registration certificate:FSB Farshim S.A.FSB Farshim S.A. Switzerland

Manufacturer: & nbsp

USB Farshim S.A. Switzerland

Representation: & nbspYUSB FARMA LLC YUSB FARMA LLC Russia

Information update date: & nbsp26.04.2016

Illustrated instructions

Instructions

Zirtek® (Zyrtec®)