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 in adults and children from 6 months of age and older for relief:

– 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.

In children 6 to 12 months of age, it should only be used as directed by a physician and under close medical supervision.

Active ingredient

Cetirizine

Composition

1 ml of the drug contains:

The active ingredient:

Cetirizine dihydrochloride – 10.00 mg

Excipients:

propylene glycol – 350.00 mg

glycerol (glycerin) – 250.00 mg

p> 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 (propyl paraben) – 0.15 mg

purified water – up to 1 ml.

How to take, the dosage

Ingestion.

The drug should be taken in the evening because symptoms are more severe in the evening.

Cetirizine can be taken with a glass of water if needed.

Cetirizine can be taken regardless of meals.

Adults: 10 mg(20 drops) once a day.

Alternatively, the dose may be divided into two doses (10 drops in the morning and evening).

Children

The use in children from 6 to 12 months is only possible by prescription and under strict medical supervision!

Children 6 to 12 months: 25 mg (5 drops) once daily.

Children 1 year to 6 years: 2.5 mg (5 drops) twice daily in the morning and evening. The duration of treatment should not exceed 4 weeks.

Children 6 to 12 years: 10 mg (20 drops) once a day.

The duration of treatment should not exceed 4 weeks.

Alternatively, the dose may be divided into two doses (10 drops in the morning and evening).

Children over 12 years of age: 10 mg (20 drops) once a day.

Sometimes an initial dose of 5 mg (10 drops) may be sufficient if satisfactory symptom control is achieved.

In children with renal insufficiency, the dose is adjusted according to CK and body weight.

Patients in elderly patients

Because of the possible reduction in renal function, the dosing regimen of the drug should be adjusted (see subsection “Patients with renal impairment” of section “Dosage and administration”).

Patients with renal failure

Because Cetirizine is mainly excreted by the kidneys (see subsection “Pharmacokinetics”) if there is no alternative treatment option for patients with renal failure the dosing regimen of the drug should be adjusted according to the renal function (creatinine clearance value – CK). The CK for men can be calculated based on serum creatinine concentration using the following formula:

The CK for women can be calculated by multiplying the resulting value by a factor of 085.

Dosing in adult patients with renal impairment:

Patients with impaired liver function

In patients with impaired liver function only, dosage adjustment is not required.

In patients with impaired hepatic and renal function, dosing adjustments are recommended (see table above).

If there is no improvement after treatment or if new symptoms occur, a physician should be consulted.

The drug should only be used according to the route of administration and in the dosage indicated.

Instructions for opening the bottle

The bottle has a first opening safety cap with child-resistant protection. The bottle opens by firmly pressing the cap down and then unscrewing it counterclockwise. After use, the cap of the bottle must be screwed back on firmly.

Interaction

Simultaneous use with azithromycin cimetidine erythromycin ketoconazole or pseudoephedrine has no effect on the pharmacokinetic parameters of cetirizine. No pharmacokinetic interactions were observed. According to in-vitro tests, cetirizine has no effect on the protein binding effect of warfarin. Simultaneous administration of azithromycin erythromycin ketoconazole theophylline and pseudoephedrine showed no significant changes in clinical laboratory indices of vital functions and ECG. In a study with concomitant administration of theophylline (400 mg daily) and cetirizine (20 mg daily), there was a slight but statistically significant increase in 24-hour AUC (area under the curve) by 19% for cetirizine and by 11% for theophylline. In addition, maximum plasma levels increased to 77 % and 64 % for cetirizine and theophylline, respectively. Simultaneously, cetirizine clearance decreased by -16% and by -10% in the case of theophylline when cetirizine was taken by patients previously treated with theophylline. However, pretreatment with cetirizine had no significant effect on the pharmacokinetic parameters of theophylline.

The effect of alcohol (08%o) was not significantly increased after a single 10-mg dose of cetirizine; a statistically significant interaction with 5 mg diazepam was proven in one of 16 psychometric tests.

Concomitant administration of 10 mg of cetirizine daily with glipizide resulted in a slight decrease in glucose values. This effect has no clinical significance. Nevertheless, separate administration – glipizide in the morning and cetirizine in the evening – is recommended. The degree of absorption of cetirizine is not reduced with simultaneous food intake, although absorption is delayed by 1 hour.

In a study with multiple administration of ritonavir (600 mg twice daily) and cetirizine (10 mg daily), cetirizine exposure was increased by approximately 40%, while ritonavir exposure was not significantly changed (-11%) due to concomitant administration of cetirizine.

Consult your doctor before using cetirizine if you are using the above or other medicines (including over-the-counter medicines).

Special Instructions

Because of the potential central nervous system depressant effects, caution should be exercised when prescribing cetirizine in children 6 months to 1 year of age if the following risk factors for sudden infant death syndrome are present, such as (but not limited to)

– sleep apnea syndrome or sudden infant death syndrome in a sibling;

– maternal drug or smoking abuse during pregnancy;

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

– abuse of smoking by nanny caregiver (one pack of cigarettes per day or more);

– Children who regularly fall asleep face down and are not placed on their backs;

– Premature (gestational age less than 37 weeks) or underweight (less than the 10th percentile of gestational age) babies;

– when concomitantly taking medications that have a depressant effect on the central nervous system.

The drug contains the excipients methyl parabenzene and propyl parabenzene which can cause allergic reactions including delayed type.

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

In patients with renal impairment the dosing regimen of the drug should be adjusted (see section “Dosage and administration”).

Because of the possible reduction of renal function in elderly patients, the dosing regimen of the drug should be adjusted (see section “Dosage and administration”).

Cautious use of cetirizine with alcohol is recommended because cetirizine may cause increased somnolence.

Caution should be exercised in patients with epilepsy and increased seizure activity.

A 3-day “washout” period is recommended before allergy testing because H1-histamine receptor blockers inhibit the development of cutaneous allergic reactions.

Please read the instructions carefully before using the medication. Retain the instructions; you may need them again. If you have any questions, talk to your doctor. The medicine you are taking is meant for you personally and should not be given to others as it can cause them harm even if they have the same symptoms as you do.

Effects on ability to drive vehicles and machines:

Cetirizine may cause increased somnolence and therefore the ability to drive vehicles and machines may be affected.

Contraindications

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

– terminal renal failure (CK < 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 insufficiency (at CK > 10 ml/min, dosing adjustment is required);

– Elderly patients (with age-related decrease in glomerular filtration);

– Epilepsy and patients with increased seizure readiness;

– Patients with predisposing factors to urinary retention (see section “Special Precautions”);

-children under 1 year of age;

– concomitant use with alcohol (see section “Interaction with other medicinal products”);

– period of breastfeeding;

– pregnancy.

Side effects

Data from clinical studies

Review

The results of clinical studies have demonstrated that the use of cetirizine in recommended doses results in the development of minor adverse CNS effects including drowsiness, fatigue, dizziness and headache. In some cases paradoxical CNS stimulation has been reported.

While cetirizine is a selective blocker of peripheral H1 receptors and has almost no anticholinergic effect, there have been single reported cases of difficulty urinating, impaired accommodation, and dry mouth.

Liver dysfunction accompanied by increased liver enzymes and bilirubin levels have been reported. In most cases the adverse events resolved after discontinuation of cetirizine.

List of adverse events

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

The following adverse reactions with an incidence of 10% or higher have been reported according to pooled analyses in placebo-controlled trials when cetirizine is used in a dose of 10 mg:

Although the incidence of somnolence in the cetirizine group was higher than that in the placebo group in most cases this adverse event was mild to moderate in severity. Objective evaluations conducted in other studies have confirmed that the use of cetirizine at the recommended daily dose in healthy young volunteers has no effect on 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:

Post-registration experience

In addition to the adverse events noted in the clinical studies and described above, the post-registration use of the drug has included the following

Non-adverse reactions.

The undesired events are listed below by MedDRA organ system class and frequency of development based on post-registration use of

the drug.

The frequency of development of adverse events was defined as follows: “infrequent” (≥ 1/1000 < 1/100); “rare” (≥ 1/10000 < 1/1000); “very rare” (< 1/10000): – frequency unknown” (cannot be estimated based on available data).

Blood and lymphatic system disorders: very rare – thrombocytopenia.

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

Metabolic and nutritional disorders: frequency is unknown – increase in appetite.

Mental disorders: infrequent – agitation; rare – aggression confusion depression hallucinations; very rare – tics; frequency unknown – suicidal ideation sleep disorders (including nightmares).

Nervous system disorders: infrequent – paresthesias; rare – seizures; very rare – perversion of taste dyskinesia dystonia syncope tremor; frequency unknown – memory disorders including amnesia deafness.

Visual disorders: very rare – accommodation disorder blurred vision nystagmus: frequency unknown – vasculitis.

Hearing and labyrinth disorders: frequency unknown – vertigo.

Cardiovascular system disorders: rare – tachycardia.

Gastrointestinal disorders: infrequent – diarrhea.

Hepatic and biliary duct disorders: rare – hepatic failure with changes in liver function tests (increased activity of transaminases of alkaline phosphatase gamma-glutamyltransferase and bilirubin); frequency is unknown – hepatitis.

Skin and subcutaneous tissue disorders: infrequent – itching rash; rare – urticaria; very rare – angioedema persistent erythema drug: frequency unknown – acute generalized exanthematous pustulosis.

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

Musculoskeletal and connective tissue disorders: frequency unknown – arthralgia.

General disorders: infrequent – asthenia malaise; rarely – peripheral edema.

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

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

It is important to report the development of adverse reactions in order to ensure continuous monitoring of the benefit-risk ratio of the drug. If any of the side effects listed in the instructions worsen or if you notice any other side effects not listed in the instructions, tell your doctor. Healthcare professionals report adverse reactions to the drug through national adverse reaction reporting systems.

Overdose

Symptoms

Symptoms observed after an apparent overdose of the drug affected the central nervous system or were associated with possible anticholinergic effects. Symptoms observed after taking at least five times the recommended daily dose included the following: confusion diarrhea fatigue headache malaise mydriasis pruritus anxiety sedation sleepiness 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 administration of activated charcoal may be effective if the overdose occurred recently. Cetirizine is partially excreted by dialysis.

Pregnancy use

Pregnancy

The data on the use of cetirizine during pregnancy are limited (300-1000 pregnancy outcomes). However, no cases of fetal and neonatal toxicity malformations with a clear causal relationship have been identified.

The experimental studies on animals did not reveal any direct or indirect adverse effects of cetirizine on the developing fetus (including in the postnatal period) during pregnancy and postnatal development. In pregnancy, cetirizine may be administered after consultation with a physician if the estimated benefit to the mother exceeds the potential risk to the fetus.

Breastfeeding period

Cetirizine should not be used during breastfeeding because cetirizine is excreted with the breast milk.

In breastfeeding, use after consultation with the physician if the expected benefit to the mother outweighs the potential risk to the baby.

Fertility

The available data on the effects on human fertility are limited but no negative effects on fertility have been found in animal studies.

Consult your doctor before using this medicine if you are pregnant or think you might be pregnant or are planning to become pregnant.

Similarities

Zyrtec, Cetrine, Zodac, Cetirizine, Cetirizine-Teva, Cetirizine drops, Solonex