Pharmacotherapeutic group: anti-allergic agent -H1-histamine receptor blocker.
ATX code: R06AE07
Mechanism of action
Cetirizine, the active ingredient in Zyrtec®, is a metabolite of hydroxyzine and has an antihistamine effect with anti-allergic action. 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-type allergic reactions. It practically does not pass through the blood-brain barrier and therefore is almost incapable of reaching central H1 receptors.
In studies of the effects of histamine on the skin, the effects of cetirizine at a dose of 10 mg began after 1 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 eosinophil excretion 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 ICAM-1 or VCAM-1;
- Inhibits the action of histaminoliberators such as PAF or Substance P.
After oral administration, the drug is rapidly absorbed from the gastrointestinal tract. The 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 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 in dose of 10 mg the maximum concentration (Cmah) in blood plasma is reached after 1 – 2 hours and is 350 ng/ml. In children after administration of cetirizine at a dose of 5 mg, the maximum plasma concentration (Cmah) 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 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 breast milk.
In adults, 60% of the dose is excreted unchanged by the kidneys.
After 10 mg administration in adults, the total clearance of cetirizine is 0.60 ml/min/kg; the half-life (T1/2) is approximately 10 hours.
The administration of multiple doses does not change the pharmacokinetic parameters. No cetirizine cumulation was observed when the drug was taken 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.
Separate patient groups
In 16 elderly individuals, the T1/2 was 50% higher and the excretion rate was 40% lower compared with the control group at a single dose of 10 mg.
The decreased clearance of cetirizine in elderly patients is probably due to decreased renal function in this patient population.
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 0.93 ml/min/kg.
The T1/2 in children 6 to 12 years old is 6 hours, 2 to 6 years old is 5 hours.
Patients with renal insufficiency:
In patients with mild renal impairment (creatinine clearance (CK) > 50 ml/min), pharmacokinetic parameters are similar to those in healthy volunteers with normal renal function.
In patients with moderate renal impairment (CKR 30 – 49 ml/min), T1/2 is prolonged 3-fold and total clearance is reduced by 70% relative to healthy volunteers with normal renal function.
In patients on hemodialysis (CK < 7 ml/min), an oral dose of 10 mg decreases total clearance by approximately 70% relative to healthy volunteers with normal renal function and prolongs T1/2 by a factor of 3.
Less than 10% of cetirizine is removed by standard hemodialysis procedures.
Patients with hepatic impairment:
In patients with chronic liver disease (hepatocellular, cholestatic, and biliary cirrhosis), a single dose of 10 or 20 mg increases T1/2 by approximately 50% and decreases clearance by 40% compared to healthy subjects.
Dose adjustment is necessary only if a patient with hepatic impairment also has concomitant renal impairment.
The use of the drug is indicated in adults and children from 6 years 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.
cetirizine dihydrochloride 10 mg.
Excipients: Microcrystalline cellulose 37.00 mg, lactose monohydrate 66.40 mg, colloidal silica 0.60 mg, magnesium stearate 1.25 mg, opadray® Y-1-7000 3.45 mg (hypromellose (E 464) 2.156 mg, titanium dioxide (E 171) 1.078 mg, macrogol 400 0.216 mg).
How to take, the dosage
The drug should be taken in the evening, since symptoms are more severe in the evening.
The drug Zyrtec® should not be chewed and it is recommended to drink water.
The drug Zyrtec® can be taken regardless of meals.
10 mg (1 tablet) once daily.
Children 6 to 12 years
10 mg (1 tablet) once daily.
The duration of treatment should not exceed 4 weeks.
Alternatively, the dose may be divided into two doses
(1/2 tablet in the morning and evening).
Children over 12 years
10 mg (1 tablet) once daily.
Sometimes an initial dose of 5 mg (1/2 tablet) may be sufficient if satisfactory symptom control can be achieved.
In children with renal insufficiency the dose is adjusted for CK and body weight.
Separate groups of patients
Because of the possible decrease in renal function, the dosing regimen of the drug should be adjusted (see Patients with renal impairment Dosage and administration
Patients with renal impairment Patients with Renal Impairment
As Zyrtec® is mainly excreted by the kidneys (see Pharmacy, section Dosage method). Pharmacokinetics), if no alternative treatment is available for patients with renal impairment, the dosing regimen of the drug should be adjusted according to renal function (creatinine clearance CK value).
The creatinine clearance (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 value obtained by a factor of 0.85.
Dosing in adult patients with renal failure
10 mg once a day
10 mg once a day
5 mg once daily
5 mg every other day
Terminal stage – patients on dialysis
taking the drug
Patients with impaired liver function
In patients with only impaired liver function, dosing 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 doses mentioned in the instructions.
Simultaneous use with azithromycin, cimetidine, erythromycin, ketoconazole or pseudoephedrine does not affect the pharmacokinetic parameters of cetirizine. No pharmacokinetic interactions have been observed. According toin vitro tests, cetirizine does not affect the protein binding effect of warfarin.
Concomitant administration of azithromycin, erythromycin, ketoconazole, theophylline and pseudoephedrine showed no significant changes in clinical laboratory parameters, vital functions and ECG.
In a study with concomitant administration of theophylline (400 mg daily) and cetirizine (20 mg daily), there was a small but statistically significant increase in 24-hour AUC (area under the curve) of 19% for cetirizine and 11% for theophylline. In addition, maximum plasma levels increased to 7.7% and 6.4% for cetirizine and theophylline, respectively. Simultaneously, cetirizine clearance decreased by -16% and also by -10% for theophylline when cetirizine was taken by patients who had previously been treated with theophylline. However, pretreatment with cetirizine had no significant effect on the pharmacokinetic parameters of theophylline.
The effect of alcohol (0.8 ‰) 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 by 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 slightly changed (-11%) due to concomitant administration of cetirizine.
If you are using the above or other medicines (including over-the-counter medications), talk to your doctor before using Zyrtec® .
In patients with spinal cord injury, prostatic hyperplasia, and in the presence of 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 lead to 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.
Cetirizine film-coated tablets should not be used in patients with hereditary galactose intolerance, lactase deficiency, or glucose-galactose malabsorption syndrome.
After discontinuation of cetirizine use, itching and/or urticaria may occur, even if these symptoms were absent at the beginning of treatment. In some cases, the symptoms may be intense and require resumption of cetirizine. Symptoms disappear when resuming cetirizine administration.
. Cetirizine film-coated tablets are contraindicated in children under 6 years of age because this dosage form does not allow for a suitable dosage for this age group. It is recommended to use the pediatric dosage form (oral drops).
Please read the instructions carefully before using this medicine. Keep the instructions; you may need them again. Ask your doctor if you have any questions. The medicine you are taking is meant for you, and you should not give it to others, because it might cause them harm, even if you have the same symptoms as you do.
Influence on driving and operating ability
Cetirizine may cause increased somnolence; therefore, the drug Zyrtec® may affect driving and operating ability.
White oblong film-coated tablets with biconvex surfaces, with a one-sided ridge and engraved “Y” on both sides of the risk.
- High sensitivity to cetirizine, hydroxyzine or other piperazine derivatives or any other component of the drug;
- terminal stage of renal failure (creatinine clearance < 10 ml/min);
- Children under 6 years of age (for this dosage form);
- Hereditary galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome.
- Elderly patients (with age-related decrease in glomerular filtration);
- Epilepsy and patients with increased seizure readiness;
- Patients with predisposing factors to urinary retention (see “Cautionary Note.
- Patients with predisposing factors to urinary retention (see
- Specific information
- Consumptive use with alcohol (see Interaction with other medicinal products
Data from clinical trials
. 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 virtually no anticholinergic effects, sporadic cases of difficulty urinating, impaired accommodation and dry mouth have been reported.
Liver dysfunction accompanied by increased liver enzymes activity and bilirubin levels have been reported. In most cases the adverse events resolved after discontinuation of cetirizine.
List of adverse reactions
. There are data available from double-blind controlled clinical trials comparing cetirizine and placebo or other antihistamines used in recommended doses (10 mg once daily for cetirizine) in more than 3,200 patients from which a reliable safety data analysis can be performed.
According to the pooled analysis, the following adverse reactions with an incidence of 1.0% or higher were identified in placebo-controlled trials when cetirizine was used in a dose of 10 mg
Cetirizine 10 mg
(n = 3260)
strong>(n = 3061)
General disorders and disorders at the point of administration
Nervous system disorders
Gastric disorders gastrointestinal tract
Pain in the abdomen
Respiratory system, thoracic and mediastinal organs disorders Far from the chest and mediastinum/em>
Although the incidence of somnolence was higher in the cetirizine group than in the placebo group, in most cases this adverse event was mild to moderate in severity. Objective evaluations in other studies have confirmed that cetirizine administration at the recommended daily dose in healthy young volunteers does not affect their daily activities.
In placebo-controlled studies, the following adverse reactions were found in children aged 6 months to 12 years with an incidence of 1% or higher:
(n = 1656)
(n = 1294)<
Gastrointestinal disorders <./em>
Respiratory system, chest and mediastinal organs
General and site disturbances
In addition to the adverse events identified in the clinical studies described above, the following adverse reactions have been observed during post-registration use of the drug.
The adverse events are listed below by MedDRA organ system class and frequency of occurrence, based on post-registration use of the drug.
The incidence of adverse events was defined as follows: Very common (≥1/10), common (≥1/100, < 1/10), infrequent (≥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 rare: thrombocytopenia
Disorders of the immune system:
Pfrequently: hypersensitivity reactions
Very rare:anaphylactic shock
Metabolic and nutritional disorders:
Frequency unknown: increased appetite
Rarely: aggression, confusion, depression, hallucinations
Very rarely: tics
Frequency unknown: suicidal ideation, sleep disturbances (including nightmares)
Nervous system disorders
Very rarely: perversion of taste, dyskinesia, dystonia, syncope, tremor
Frequency unknown: memory impairment, including amnesia, deafness
Very rare: Accommodation disorder, blurred vision, nystagmus
Frequency unknown: vasculitis
Hearing and labyrinth disorders
Frequency unknown: vertigo
.Gastrointestinal tract disorders
Liver and bile duct disorders
Rarely:hepatic failure with altered liver function tests (increased activity of transaminases, alkaline phosphatase, gamma-glutamyltransferase, and bilirubin)
Frequency unknown: Hepatitis
Skin and subcutaneous tissue disorders
Infrequent: rash, itching
Very rare: angioneurotic edema, persistent drug erythema
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
Infrequent: asthenia, malaise
Rarely: peripheral edema
Influence on laboratory and instrumental findings
Rarely: increase in body weight
Description of individual adverse reactions
Cases of pruritus, (including intense itching) and/or urticaria have been reported after discontinuation of cetirizine.
If you experience or worsen the side effects listed in the instructions, or if you notice any other side effects not listed in the instructions, tell your doctor.
Symptoms observed after an apparent drug overdose 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, itching, anxiety, sedation, somnolence, stupor, tachycardia, tremor, and urinary retention.
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.
The data on the use of cetirizine during pregnancy are limited (300-1000 pregnancy outcomes). However, no cases of malformations, fetal and neonatal toxicity 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), the course of pregnancy and labor.
In pregnancy, cetirizine may be administered after consultation with a physician if the anticipated benefit to the mother exceeds the potential risk to the fetus.
Cetirizine should not be used during breastfeeding because cetirizine is excreted with breast milk. Cetirizine is excreted in breast milk in the amount of 25-90% of the concentration in blood plasma, depending on the time of sampling after taking the drug. Adverse reactions associated with cetirizine may be observed in infants.
In the period of breastfeeding, use after consultation with a physician if the anticipated benefit to the mother exceeds the potential risk to the baby.
The available data on effects on human fertility are limited, but negative effects on fertility have not been identified in animal studies.
Consult your doctor before using the drug if you are pregnant, or if you think you might be pregnant, or are planning a pregnancy.
Zyrtec, Cetrine, Zodac, Cetirizine, Cetirizine-Teva, Cetirizine drops, Solonex
5 years. Do not take after the expiration date.
|Conditions of storage|
At a temperature not exceeding 30 oC. Keep out of reach of children.
UCB Farma, Belgium
Buy Zyrtec, 10 mg 30 pcs with delivery to USA, UK, Europe and over 120 other countries.