Cetirizine-Vertex, 10 mg 20 pcs

Indications

The use of the drug is indicated in adults and children over 6 years of age to alleviate:
nasal and ocular symptoms of year-round (persistent) and seasonal (intermittent) allergic rhinitis and allergic conjunctivitis, such as itching, sneezing, nasal congestion, rhinorrhea, lacrimation, conjunctival hyperemia;
symptoms of chronic idiopathic urticaria.

Pharmacological effect

Pharmacotherapeutic group

Antiallergic agent – ​​H1-histamine receptor blocker.

ATX code

R06AE07

Pharmacological properties

Pharmacodynamic properties

Mechanism of action

Cetirizine, the active substance of the drug, is a metabolite of hydroxyzine, 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. Almost does not pass the blood-brain barrier and, therefore, is almost unable to reach the 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 at 1 hour, peaked at 2 to 12 hours, and were still observed at statistically significant levels at 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 daily, 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 ICAM-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, the maximum concentration (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 0.60 ml/min/kg; The half-life (T½) is approximately 10 hours. Taking multiple doses does not change pharmacokinetic parameters. When taking cetirizine 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 individuals, with a single dose of cetirizine 10 mg, T½ 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 0.93 ml/min/kg.

T½ for children from 6 to 12 years old is 6 hours, from 2 to 6 years old – 5 hours.

Patients with renal failure:

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

In patients with moderate renal failure (creatinine clearance 30-49 ml/min), T½ 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 cetirizine is taken orally at a dose of 10 mg, the total clearance is reduced by approximately 70% relative to healthy volunteers with normal renal function, and T½ 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 cetirizine at a dose of 10 or 20 mg, T½ 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

In patients with spinal cord injury, prostatic hyperplasia, or other predisposing factors 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”).
Caution is recommended 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.
Cetirizine film-coated tablets should not be administered to patients with hereditary lactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome.
After stopping the use of cetirizine, itching and/or urticaria may occur, even if these symptoms were absent at the beginning of treatment. In some cases, symptoms may be severe and require resumption of cetirizine. Symptoms disappear when cetirizine is resumed.

Children
Cetirizine film-coated tablets are contraindicated in children under 6 years of age, since this dosage form does not allow the use of an appropriate dosage for this age group. It is recommended to use the pediatric dosage form (oral drops).
Read the instructions carefully before you start using the drug. Save the instructions, 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 given to others as it may cause harm to them even if they have the same symptoms as you.

Impact on the ability to drive vehicles and machinery
Cetirizine can lead to increased drowsiness, therefore, the drug may affect the ability to drive vehicles and machinery.

Active ingredient

Cetirizine

Composition

One tablet contains:

active ingredient: cetirizine dihydrochloride – 10.0 mg;

excipients: lactose monohydrate – 70.0 mg; microcrystalline cellulose – 34.0 mg; crospovidone – 3.6 mg; magnesium stearate – 1.2 mg; colloidal silicon dioxide – 1.2 mg;

film coating: [hypromellose – 2.40 mg, talc – 0.80 mg, titanium dioxide – 0.44 mg, macrogol 4000 (polyethylene glycol 4000) – 0.36 mg] or [dry film coating mixture containing hypromellose (60%), talc (20%), titanium dioxide (11%), macrogol 4000 (polyethylene glycol 4000) (9%)] – 4.0 mg.

Pregnancy

Pregnancy

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

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

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, because Cetirizine is excreted in breast milk in amounts ranging from 25% to 90% of the plasma concentration, depending on the time of sampling after taking the drug. Adverse reactions associated with cetirizine may occur in infants.

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, but no adverse 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, as well as any other components of the drug;
moderate, severe and end-stage renal failure (creatinine clearance <50 ml/min) (for this dosage); children under 6 years of age (for this dosage form); hereditary lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome. With caution
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”);
when used simultaneously with alcohol (see section “Interaction with other drugs”);
pregnancy;
breastfeeding period.

Side Effects

Data obtained in 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.

Liver dysfunction has been reported, accompanied by elevated liver enzymes and bilirubin levels. In most cases, adverse events resolved after discontinuation of cetirizine.

List of unwanted side reactions

Data are available from double-blind, controlled clinical trials comparing cetirizine with placebo or other antihistamines administered at recommended doses (10 mg once daily for cetirizine) in more than 3200 patients from which reliable safety data can be analyzed.

According to the results of the pooled analysis, in placebo-controlled studies with cetirizine 10 mg, the following adverse reactions were detected with an incidence of 1.0% or higher.

Adverse reactions (WHO terminology)

Cetirizine 10 mg (n = 3260)

Placebo

(n = 3061)

General disorders and reactions at the injection site

Fatigue

1.63%

0.95%

Nervous system disorders

Dizziness

Headache

1.10%

7.42%

0.98%

8.07%

Gastrointestinal disorders

Abdominal pain

Dry mouth

Nausea

0.98%

2.09%

1.07%

1.08%

0.82%

1.14%

Mental disorders

Drowsiness

9.63%

5.00%

Respiratory, thoracic and mediastinal disorders

Pharyngitis

1.29%

1.34%

Although the incidence of somnolence in the cetirizine group was higher than that in the placebo group, most cases were mild or moderate in severity. When objectively assessed in other studies, it was 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 10 mg (n = 1656)

Placebo

(n = 1294)

Gastrointestinal disorders

Diarrhea

1.0%

0.6%

Mental disorders

Drowsiness

1.8%

1.4%

Respiratory, thoracic and mediastinal disorders

Rhinitis

1.4%

1.1%

General disorders and reactions at the injection site

Fatigue

1.0%

0.3%

Post-registration experience

In addition to the adverse events identified during clinical trials and described above, the following adverse reactions were observed during post-marketing use of cetirizine.

Adverse events are presented below by MedDRA organ system class and incidence based on post-marketing data for cetirizine. The incidence of adverse events was determined as follows: very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1000, < 1/100), rare (≥ 1/10000, < 1/1000), very rare (< 1/10000), frequency unknown (due to insufficient data).

Blood and lymphatic system disorders:

very rarely – thrombocytopenia.

Immune system disorders:

rarely – hypersensitivity reactions;

very rarely – anaphylactic shock.

Metabolic and nutritional disorders:

frequency unknown – increased appetite.

Mental disorders:

infrequently – excitement;

rarely – aggression, confusion, depression, hallucinations;

very rarely – tic;

frequency unknown – suicidal ideation, sleep disturbances (including nightmares).

Nervous system disorders:

infrequently – paresthesia;

rarely – convulsions;

very rarely – taste perversion, dyskinesia, dystonia, fainting, tremor;

frequency unknown – memory impairment, including amnesia, deafness.

Visual disorders:

very rarely – disturbance of accommodation, blurred vision, nystagmus;

frequency unknown – vasculitis.

Disorders of the hearing organ and labyrinth:

frequency unknown – vertigo.

Cardiac disorders:

rarely – tachycardia.

Gastrointestinal disorders:

infrequently – diarrhea.

Disorders of the liver and biliary tract:

rarely – liver failure with changes in liver function tests (increased activity of transaminases, alkaline phosphatase, gamma-glutamyltransferase and bilirubin);

frequency unknown – hepatitis.

Skin and subcutaneous tissue disorders:

uncommon – rash, itching;

rarely – urticaria;

very rarely – angioedema, persistent drug-induced erythema;

frequency unknown – acute generalized exanthematous pustulosis.

Muscle, skeletal and connective tissue disorders:

frequency unknown – arthralgia.

Renal and urinary tract disorders:

very rarely – dysuria, enuresis;

frequency unknown – urinary retention.

General disorders and reactions at the injection site:

infrequently – asthenia, malaise;

rarely – peripheral edema.

Laboratory and instrumental data:

rarely – weight gain.

Description of selected adverse reactions

Cases of pruritus (including intense pruritus) and/or urticaria have been reported following discontinuation of cetirizine.

If you experience the side effects listed in the instructions or they get worse, or you notice any other side effects not listed in the instructions, tell your doctor.

Interaction

Concomitant use with azithromycin, cimetidine, erythromycin, ketoconazole or pseudoephedrine does not affect the pharmacokinetic parameters of cetirizine. No pharmacokinetic interactions were observed. According to in vitro testing, cetirizine does not interfere with the protein binding effect of warfarin.
Concomitant use of azithromycin, erythromycin, ketoconazole, theophylline or pseudoephedrine did not reveal significant changes in clinical laboratory parameters, 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 7.7% and 6.4%, 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 (0.8 ‰) 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, it is recommended to take it separately – 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 the drug.

Overdose

Symptoms

Symptoms observed after apparent overdose of cetirizine affected the central nervous system or were associated with a possible anticholinergic effect.

Symptoms that were observed after taking at least five times the recommended daily dose included the following: confusion, diarrhea, fatigue, headache, malaise, mydriasis, itching, restlessness, sedation, somnolence, 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 is recent. Cetirizine is partially eliminated by dialysis.

Storage conditions

Store in a place protected from light at a temperature not exceeding 25 ºС.

Keep out of the reach of children.

Shelf life

3 years.

Do not use after expiration date.

Manufacturer

Vertex, Russia