Cetirizine, drops 10 mg/ml 20 ml

Pharmacotherapeutic group

Anti-allergic agent – H1-histamine receptor blocker

ATC code

R06AE07

Pharmacodynamics:

Mechanism of action

Cetirizine is a metabolite of hydroxyzine has an antihistamine effect with anti-allergic effects. Cetirizine belongs to the group of competitive histamine antagonists and blocks H1-histamine receptors with little effect on other receptors and has almost no anticholinergic and antiserotonin action.

Cetirizine affects the histamine-dependent stage of immediate allergic reactions and also reduces the migration of eosinophils and limits the release of mediators in delayed allergic reactions. It practically does not pass through the blood-brain barrier and therefore is almost incapable of reaching central H1 receptors.

Pharmacodynamics

In studies of the effects of histamine on the skin, the effects of cetirizine at a dose of 10 mg began after I hour, peaked from the 2nd to 12th hour, and were still observed at statistically significant levels after 24 hours. In addition to its antihistamine effect, cetirizine also has an anti-inflammatory effect and thus has an effect on the late phase of the allergic reaction:

– At a dose of 10 mg once or twice daily, it inhibits the late phase of eosinophil aggregation in the skin;

– At a dose of 30 mg daily, it inhibits the release of eosinophils into the bronchial alveolar fluid after allergen-induced bronchial constriction;

– Inhibits the kallikrein-induced late inflammatory response;

– Inhibits the expression of inflammatory markers such as 1CAM-1 or VCAM-1;

– Inhibits the action of histaminoliberators such as PAF or Substance P.

Pharmacokinetics:

Intake

After oral administration, the drug is rapidly absorbed from the gastrointestinal tract. Pharmacokinetic parameters of cetirizine change linearly when administered in doses from 5 to 60 mg. The equilibrium concentration is reached after 3 days.

The pharmacokinetic profile of cetirizine is similar in adults and children. In children after taking cetirizine in a dose of 5 mg, the concentration of the active substance in the body is the same as in adults after taking 10 mg. In adults after taking cetirizine in dose of 10 mg the maximum concentration (Cmax) in blood plasma is reached after 1-2 hours and is 350 ng/ml. In children after cetirizine administration in a dose of 5 mg the Cmax in blood plasma is reached after 1 hour and is 275 ng/ml.

When cetirizine is taken in the form of drops, maximum plasma concentrations are reached at a higher rate.

Distribution

Distribution after 10 mg administration is 35 liters in adults and plasma protein binding is 93%. In children, the volume of distribution after administration of 5 mg is approximately 17 liters.

A small amount of cetirizine is excreted into the breast milk.

Metabolism

In adults, 60% of the dose is excreted unchanged by the kidneys.

Elevation

After 10 mg administration in adults, the total clearance of cetirizine is 060 ml/min/kg; the half-life (T1/2) is approximately 10 hours. Multiple doses do not alter pharmacokinetic parameters. No cetirizine cumulation was observed when taking the drug in a daily dose of 10 mg for 10 days.

After the end of treatment, plasma levels of cetirizine rapidly fall below detectable limits. Repeated allergy tests can be resumed after 3 days.

Particular patient groups

Elderly patients:

The T1/2 was 50% higher and the excretion rate was 40% lower in 16 elderly persons at a single dose of 10 mg compared with the control group.

The decreased clearance of cetirizine in elderly patients is probably due to decreased renal function in this patient population.

Children:

In children aged 6 to 12 years, 70% of the dose is excreted unchanged by the kidneys.

After administration of 5 mg in children, the total clearance of cetirizine is 093 ml/min/kg. The T1/2 in children 6 to 12 years old is 6 hours 2 to 6 years old is 5 hours 6 months to 2 years old is reduced to 31 hours.

Patients with renal insufficiency:

In patients with mild renal impairment (creatinine clearance (CK) > 50 mL/min), pharmacokinetic parameters are similar to those of healthy volunteers with normal renal function.

In patients with moderate renal impairment (CKD 30-49 ml/min), the T1/2 is prolonged 3-fold and total clearance is decreased by 70% compared to healthy volunteers with normal renal function.

In patients on hemodialysis (KC < 7 ml/min), when administered orally at a dose of 10 mg, total clearance is decreased approximately 70% compared to healthy volunteers with normal renal function and T1/2 is prolonged 3-fold.

Less than 10% of cetirizine is eliminated by standard hemodialysis procedures.

Patients with hepatic insufficiency:

In patients with chronic liver disease (hepatocellular cholestatic and biliary cirrhosis), a single dose of 10 or 20 mg increases the T1/2 by approximately 50% and decreases clearance by 40% compared to healthy subjects.

Dose adjustment is necessary only if the patient with hepatic impairment also has concomitant renal impairment.

Indications

The drug is indicated for adults and children from 6 months and older to relieve:

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

– symptoms of chronic idiopathic urticaria.

Use in children from 6 to 12 months is possible only as prescribed by a doctor and under strict medical supervision.

Pharmacological effect

Pharmacotherapeutic group

Antiallergic agent – H1-histamine receptor blocker

ATX code

R06AE07

Pharmacodynamics:

Mechanism of action

Cetirizine is a metabolite of hydroxyzine and has an antihistamine effect with an antiallergic effect. Cetirizine belongs to the group of competitive histamine antagonists and blocks H1-histamine receptors with little effect on other receptors and has virtually no anticholinergic and antiserotonin effects.

Cetirizine has an effect on the histamine-dependent stage of immediate-acting allergic reactions and also reduces the migration of eosinophils and limits the release of mediators in delayed-type allergic reactions. Practically does not pass through the blood-brain barrier and is therefore almost unable to reach the central H1 receptors.

Pharmacodynamics

In studies of the effects of histamine on the skin, the effect of cetirizine at a dose of 10 mg began after 1 hour, reached a maximum from the 2nd to the 12th hour and was still observed at statistically significant levels after 24 hours. In addition to the antihistamine effect, cetirizine also has an anti-inflammatory effect and thereby affects the late phase of the allergic reaction:

– at a dose of 10 mg once or twice a day, inhibits the late phase of eosinophil aggregation in the skin;

– at a dose of 30 mg per day inhibits the excretion of eosinophils into the bronchial alveolar fluid after allergen-induced bronchial constriction;

– inhibits the late inflammatory response caused by kallikrein;

– suppresses the expression of inflammatory markers such as 1CAM-1 or VCAM-1;

– inhibits the action of histamine liberators such as PAF or substance P.

Pharmacokinetics:

Suction

After oral administration, the drug is quickly absorbed from the gastrointestinal tract. The pharmacokinetic parameters of cetirizine when used in doses from 5 to 60 mg change linearly. Equilibrium concentration is achieved after 3 days.

The pharmacokinetic profile of cetirizine is similar in adults and children. In children, after taking cetirizine at a dose of 5 mg, the concentration of the active substance in the body is the same as in adults after taking 10 mg. In adults, after taking cetirizine at a dose of 10 mg, the maximum concentration (Cmax) in the blood plasma is reached after 1-2 hours and is 350 ng/ml. In children, after taking cetirizine at a dose of 5 mg, Cmax in the blood plasma is reached after 1 hour and is 275 ng/ml.

When cetirizine is taken in the form of drops, maximum plasma concentrations are achieved at a higher rate.

Distribution

Distribution after taking 10 mg is 35 liters in adults and binding to plasma proteins is 93%. In children, the volume of distribution after taking 5 mg is approximately 17 liters.

A small amount of cetirizine is excreted into breast milk.

Metabolism

In adults, 60% of the dose is excreted unchanged from the body by the kidneys.

Removal

After taking 10 mg in adults, the total clearance of cetirizine is 060 ml/min/kg; The half-life (T1/2) is approximately 10 hours. Taking multiple doses does not change pharmacokinetic parameters. When taking the drug at a daily dose of 10 mg for 10 days, no accumulation of cetirizine was observed.

After the end of treatment, the level of cetirizine in the blood plasma quickly falls below detectable limits. Repeated allergy tests can be resumed after 3 days.

Selected patient groups

Elderly patients:

In 16 elderly people, with a single dose of 10 mg of the drug, T1/2 was 50% higher and the elimination rate was 40% lower compared to the control group.

The decreased clearance of cetirizine in elderly patients is likely due to decreased renal function in this category of patients.

Children:

In children aged 6 to 12 years, 70% of the dose is excreted unchanged from the body by the kidneys.

After taking 5 mg in children, the total clearance of cetirizine is 093 ml/min/kg. T1/2 in children from 6 to 12 years is 6 hours; from 2 to 6 years – 5 hours from 6 months to 2 years – reduced to 31 hours.

Patients with renal failure:

In patients with mild renal failure (creatinine clearance (CC) > 50 ml/min), pharmacokinetic parameters are similar to those of healthy volunteers with normal renal function.

In patients with moderate renal failure (creatinine clearance 30-49 ml/min), T1/2 is prolonged by 3 times and total clearance is reduced by 70% relative to healthy volunteers with normal renal function.

In patients on hemodialysis (creatinine clearance <7 ml/min), when taking the drug orally at a dose of 10 mg, the total clearance is reduced by approximately 70% relative to healthy volunteers with normal renal function and T1/2 is extended by 3 times.

Less than 10% of cetirizine is removed during standard hemodialysis.

Patients with liver failure:

In patients with chronic liver diseases (hepatocellular cholestatic and biliary cirrhosis), with a single dose of 10 or 20 mg, T1/2 increases by approximately 50% and clearance decreases by 40% compared to healthy subjects.

Dose adjustment is only necessary if the patient with hepatic insufficiency also has concomitant renal insufficiency.

Special instructions

Due to the potential depressant effect on the central nervous system, caution should be exercised when prescribing Cetirizine to children aged 6 months to 1 year who have the following risk factors for sudden infant death syndrome, such as (but not limited to):

– sleep apnea syndrome or sudden infant death syndrome in a brother or sister;

– maternal drug abuse or smoking during pregnancy;

– young age of mother (19 years and younger);

– smoking abuse by a nanny caring for a child (one pack of cigarettes a day or more);

– children who regularly fall asleep face down and are not placed on their back;

– premature (gestational age less than 37 weeks) or low birth weight (below the 10th percentile of gestational age) children;

– when taking drugs together that have a depressing effect on the central nervous system.

The preparation contains excipients methylparabenzene and propylparabenzene, which can cause allergic reactions, including delayed ones.

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

In patients with renal failure, the dosage regimen of the drug should be adjusted (see section “Dosage and Administration”).

Due to a possible decrease in renal function in elderly patients, the dosage regimen of the drug should be adjusted (see section “Dosage and Administration”).

It is recommended to be careful when using cetirizine concomitantly with alcohol, as cetirizine may cause increased drowsiness.

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

Before prescribing allergy tests, a three-day “washing out” period is recommended due to the fact that H1-histamine receptor blockers inhibit the development of skin allergic reactions.

Read the instructions carefully before you start using the drug. Save the instructions as you may need them again. If you have any questions, consult your doctor. The medicine you are being treated with is intended for you personally and should not be shared with others as it may cause harm to them even if they have the same symptoms as you.

Impact on the ability to drive vehicles. Wed and fur.:

Cetirizine may cause increased drowsiness; therefore, Cetirizine may affect the ability to operate vehicles.

Active ingredient

Cetirizine

Composition

1 ml of the drug contains:

Active ingredient:

Cetirizine dihydrochloride – 10.00 mg

Excipients:

propylene glycol – 350.00 mg

glycerol (glycerol) – 250.00 mg

sodium acetate trihydrate – 10.00 mg

sodium saccharinate – 10.00 mg

methyl parahydroxybenzoate (methylparaben) – 1.35 mg

glacial acetic acid – 0.53 mg

propyl parahydroxybenzoate (propylparaben) – 0.15 mg

purified water – up to 1 ml.

Pregnancy

Pregnancy

Data on the use of cetirizine during pregnancy are limited (300-1000 pregnancy outcomes). However, no cases of developmental defects of embryonic and neonatal toxicity with a clear cause-and-effect relationship have been identified.

Experimental studies in animals have not revealed any direct or indirect adverse effects of cetirizine on the developing fetus (including in the postnatal period), pregnancy and postnatal development. During pregnancy, cetirizine can be prescribed after consultation with a doctor if the expected benefit to the mother outweighs the potential risk to the fetus.

Breastfeeding period

Cetirizine should not be used during breastfeeding since cetirizine is excreted in breast milk.

During breastfeeding, it is used after consultation with a doctor if the expected benefit to the mother outweighs the potential risk to the child.

Fertility

Available data on the effects on human fertility are limited; however, no negative effects on fertility have been identified in animal studies.

Before using the drug, if you are pregnant or think you might be pregnant or are planning a pregnancy, you should consult your doctor.

Contraindications

– Hypersensitivity to cetirizine hydroxyzine or other piperazine derivatives or any other component of the drug;

– end-stage renal failure (CC < 10 ml/min);

– children under 6 months of age (due to limited data on the effectiveness and safety of the drug Cetirizine).

With caution:

– Chronic renal failure (with CC > 10 ml/min, dosage regimen adjustment is required);

– elderly patients (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”);

– children under 1 year of age;

– when used simultaneously with alcohol (see section “Interaction with other drugs”);

– breastfeeding period;

– pregnancy.

Side Effects

Data obtained from clinical studies

Review

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

Despite the fact that cetirizine is a selective blocker of peripheral H1 receptors and has virtually no anticholinergic effect, isolated cases of difficulty urinating, disturbances of accommodation and dry mouth have been reported.

Impaired liver function has been reported, accompanied by increased activity of liver enzymes and bilirubin levels. In most cases, adverse events resolved after discontinuation of cetirizine.

List of unwanted side effects

There is data obtained from double-blind, controlled clinical studies comparing cetirizine with placebo or other antihistamines used at recommended doses (10 mg once daily for cetirizine) in more than 3200 patients, on the basis of which a reliable analysis of safety data can be carried out.

According to the results of a pooled analysis of placebo-controlled studies with cetirizine 10 mg, the following adverse reactions were identified with a frequency of 10% or higher:

Adverse reactions (WHO terminology)

Cetirizine (n=3260)

Placebo (n=3061)

General disorders and disorders at the injection site

Fatigue

163%

095%

Nervous system disorders

Dizziness

110%

098%

Headache

742%

807%

Gastrointestinal disorders

Abdominal pain

098%

108%

Dry mouth

209%

082%

Nausea

107%

114%

Mental disorders

Drowsiness

963%

500%

Disorders of the respiratory system of the chest and mediastinum

Pharyngitis

129%

134%

Although the incidence of somnolence in the cetirizine group was higher than that in the placebo group, most of the adverse events were mild or moderate in severity. Objectively assessed in other studies, it has been confirmed that the use of cetirizine at the recommended daily dose in healthy young volunteers does not affect their daily activities.

Children

In placebo-controlled studies in children aged 6 months to 12 years, the following adverse reactions were identified with an incidence of 1% or higher:

Adverse reactions (WHO terminology)

Cetirizine (n=1656)

Placebo (n=1294)

Gastrointestinal disorders

Diarrhea

10%

06%

Mental disorders

Drowsiness

18%

14%

Disorders of the respiratory system of the chest and mediastinum

Rhinitis

14%

11%

General disorders and disorders at the injection site

Fatigue

10%

03%

Post-registration experience

In addition to the adverse events identified during clinical trials and described above, during post-registration use of the drug,

no unwanted reactions follow.

Adverse events are presented below by MedDRA system organ class and incidence based on post-marketing data.

drug.

The incidence of adverse events was defined as follows: “uncommon” (≥ 1/1000 < 1/100); "rare" (≥ 1/10000 < 1/1000); “very rare” (< 1/10000): - frequency unknown” (cannot be estimated from available data).

Disorders of the blood and lymphatic system: very rarely – thrombocytopenia.

Immune system disorders: rarely – hypersensitivity reactions; very rarely – anaphylactic shock.

Metabolic and nutritional disorders: frequency unknown – increased appetite.

Mental disorders: infrequently – agitation; rarely – aggression, confusion, depression, hallucinations; very rarely – tic; frequency unknown – suicidal ideation, sleep disturbances (including nightmares).

Nervous system disorders: uncommon – paresthesia; rarely – convulsions; very rarely – taste perversion, dyskinesia, dystonia, fainting, tremor; frequency unknown – memory impairment including amnesia, deafness.

Visual disturbances: very rarely – disturbance of accommodation, blurred vision, nystagmus: frequency unknown – vasculitis.

Hearing and labyrinthine disorders: frequency unknown – vertigo.

Cardiovascular system disorders: rarely – tachycardia.

Gastrointestinal disorders: infrequently – diarrhea.

Disorders of the liver and bile ducts: rarely – liver failure with changes in liver function tests (increased activity of transaminases alkaline phosphatase gamma-glutamyltransferase and bilirubin); frequency unknown – hepatitis.

Disorders of the skin and subcutaneous tissues: uncommon – rash, itching; rarely urticaria; very rarely – angioedema; persistent drug erythema; frequency unknown – acute generalized exanthematous pustulosis.

Renal and urinary tract disorders: very rarely – dysuria, enuresis; frequency unknown – urinary retention.

Musculoskeletal and connective tissue disorders: frequency unknown – arthralgia.

General disorders: infrequently – asthenia, malaise; rarely – peripheral edema.

Impact on the results of laboratory and instrumental studies: rarely – increased body weight.

Description of selected adverse reactions: after discontinuation of cetirizine, cases of itching, including intense itching and/or urticaria, have been reported.

It is important to report the development of adverse reactions to ensure continuous monitoring of the benefit-risk ratio of the drug. If any of the side effects indicated in the instructions get worse or you notice any other side effects not listed in the instructions, tell your doctor. Health care professionals report adverse drug reactions through national adverse event reporting systems.

Interaction

Concomitant use with azithromycin, cimetidine, erythromycin, ketoconazole or pseudoephedrine does not affect the pharmacokinetic parameters of cetirizine. No pharmacokinetic interactions were observed. In vitro testing shows that cetirizine does not interfere with the protein binding effect of warfarin. Concomitant administration of azithromycin erythromycin ketoconazole theophylline and pseudoephedrine did not reveal significant changes in clinical laboratory vital signs and ECG. In a study of co-administration of theophylline (400 mg per day) and cetirizine (20 mg per day), a small but statistically significant increase in 24-hour AUC (area under the curve) was found by 19% for cetirizine and 11% for theophylline. In addition, maximum plasma levels increased to 77% and 64%, respectively, for cetirizine and theophylline. At the same time, the clearance of cetirizine decreased by -16% and also by -10% in the case of theophylline when cetirizine was taken by patients who had previously received treatment with theophylline. However, pretreatment with cetirizine did not have a significant effect on the pharmacokinetic parameters of theophylline.

After a single dose of cetirizine 10 mg, the effect of alcohol (08% o) was not significantly enhanced; a statistically significant interaction with 5 mg diazepam was demonstrated in one of 16 psychometric tests.

Concomitant administration of 10 mg cetirizine per day with glipizide resulted in a slight decrease in glucose levels. This effect is not clinically significant. However, separate administration is recommended – glipizide in the morning and cetirizine in the evening. The degree of absorption of cetirizine is not reduced by simultaneous ingestion of food, although absorption slows down by 1 hour.

In a multiple-dose study of ritonavir (600 mg twice daily) and cetirizine (10 mg daily), cetirizine exposure was increased by approximately 40%, while ritonavir exposure was slightly changed (-11%) due to concomitant use of cetirizine.

If you are using the above or other medications (including over-the-counter medications), consult your doctor before using Cetirizine.

Overdose

Symptoms

Symptoms observed after apparent overdose of the drug affected the central nervous system or were associated with a possible anticholinergic effect. Symptoms observed after taking at least five times the recommended daily dose included the following: confusion diarrhea fatigue headache malaise mydriasis itching restlessness sedation drowsiness stupor tachycardia tremor urinary retention.

Treatment

There is no specific antidote.

In case of overdose, symptomatic or supportive treatment is recommended. Gastric lavage and/or activated charcoal may be effective if the overdose has occurred recently. Cetirizine is partially eliminated by dialysis.

Storage conditions

In a pack at a temperature not exceeding 25 °C.

Keep out of the reach of children.

Shelf life

3 years.

Do not use after expiration date.

Manufacturer

Ozon, Russia