Cetirizine Reneval, drops 10 mg/ml 20 ml

Pharmacotherapeutic group: anti-allergic agent – H₁-histamine receptor blocker.

ATX code: R06AE07

Pharmacological properties

Mechanism of action

p> Cetirizine is a metabolite of hydroxyzine and 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-type 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 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, inhibits the late phase of eosinophil aggregation in the skin;

– at a dose of 30 mg daily, 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 ICAM-1 or VCAM-1;

inhibits the action of histaminoliberators such as PAF or Substance P.

Pharmacokinetics

absorption

After oral administration, the drug is rapidly absorbed from the gastrointestinal
tract. The pharmacokinetic parameters of cetirizine change linearly when administered in doses
of 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 at a dose of 10 mg the maximum concentration (C_max)
in blood plasma is reached after 1-2 hours and is 350 ng/ml. In children after
ingestion of cetirizine at a dose of 5 mg C_max in 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 breast milk.

Metabolism

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

Elimation

After 10 mg administration in adults, total clearance of cetirizine is
0.60 ml/min/kg; the half-life (T_1/2) is approximately 10 hours.
Administration of multiple doses does not change 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
fall rapidly below detectable limits. Repeated allergy
tests can be resumed after 3 days.

Separate patient groups

Elderly patients:

The 16 elderly patients had a T_1/2 higher
by 50% and a 40% lower excretion rate compared with the control
group when they took the drug 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.

Children:

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

After administration of 5 mg in children, the total clearance of cetirizine is
0.93 ml/min/kg.

T_1/2 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 3.1 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 insufficiency (CKD 30-49 ml/min), the T_1/2 lengthens by a factor of 3 and total clearance decreases by 70% relative to healthy volunteers with normal renal function.

In patients on hemodialysis (CK < 7 ml/min), oral administration of the drug
at a dose of 10 mg decreases total clearance by approximately 70%
relative to healthy volunteers with normal renal function, and the T_1/2 lengthens
3-fold.

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

Patients with hepatic insufficiency:

In patients with chronic liver disease (hepatocellular, cholestatic, and biliary cirrhosis), a single dose of the drug
at a dose of 10 or 20 mg, the T_1/2 is increased by approximately 50% and clearance is decreased
by 40% compared to healthy subjects.

Dose adjustment is necessary only if a 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

Pharmacological properties

Mechanism of action

Cetirizine 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 skin, the effects of cetirizine 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 its antihistamine effect, cetirizine also has anti-inflammatory properties.
effect and thereby influences 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 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.
tract. Pharmacokinetic parameters of cetirizine when used in doses
from 5 to 60 mg change linearly. Equilibrium concentration is achieved
in 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 active
substances in the body are the same as in adults after taking 10 mg. In adults
after taking cetirizine at a dose of 10 mg maximum concentration (Cmax)
in 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 blood plasma is achieved 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, volume of distribution after administration of 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 (T1/2) is approximately 10 hours.
Taking multiple doses does not change pharmacokinetic parameters. When taking the drug in a daily dose of 10 mg for 10 days, cetirizine accumulates
was not observed.

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

Selected patient groups

Elderly patients:

In 16 elderly people, with a single dose of the drug at a dose of 10 mg, T1/2 was higher
by 50%, and the excretion 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
kidneys.

After taking 5 mg in children, the total clearance of cetirizine is
0.93 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 3.1 hours.

Patients with renal failure:

In patients with mild renal failure (clearance
creatinine (CC) > 50 ml/min) pharmacokinetic parameters are similar
those in 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, total clearance is reduced by approximately 70%
relatively healthy volunteers with normal renal function, and T1/2 is prolonged
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 the drug
at a 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 for central nervous system depressant effects, caution should be exercised when prescribing Cetirizine Renewal 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 sibling;
maternal drug abuse or smoking during pregnancy;
young maternal age (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 depressant effect on the central nervous system.

The drug contains excipients methyl parahydroxybenzoate and propyl parahydroxybenzoate, which can cause allergic reactions, including delayed ones.

In patients with spinal cord injury, prostatic hyperplasia,
and in the presence of other factors predisposing to urinary retention, caution is required, since 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.

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 using 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 Cetirizine Renewal may affect the ability to drive vehicles and machinery.

Active ingredient

Cetirizine

Composition

1 ml of the drug contains:
Active ingredient: cetirizine dihydrochloride – 10.00 mg; excipients: propylene glycol, glycerol (glycerin), sodium acetate trihydrate, sodium saccharinate, methyl parahydroxybenzoate (methylparaben), glacial acetic acid, propyl parahydroxybenzoate (propylparaben), purified water

Pregnancy

Pregnancy

Data on the use of cetirizine during pregnancy are limited
(300-1000 pregnancy outcomes). However, no cases of formation of
malformations, embryonic and neonatal toxicity with clear
cause-and-effect relationship.

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

During pregnancy, cetirizine can be prescribed after consultation with a doctor,
if the expected benefit to the mother exceeds the potential
risk to the fetus.

Breastfeeding period

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

During breastfeeding, use 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 demonstrated in animal studies.

Before using the drug if you are pregnant or think you might be
If you are pregnant, or are planning a pregnancy, you need to consult
with a doctor.

Contraindications

Hypersensitivity to cetirizine, hydroxyzine or other piperazine derivatives, as well as any other component of the drug;
end-stage renal failure (CC < 10 ml/min); children up to 6 months of age (due to limited data on the effectiveness and safety of the drug Cetirizine Renewal).

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 medicines”);
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, reported
about isolated cases of difficulty urinating, disturbances of accommodation and dry mouth.

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

List of unwanted side effects

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

According to the results of the pooled analysis, in placebo-controlled studies with the use of cetirizine at a dose of 10 mg, the following adverse reactions were identified with a frequency of 1.0% or higher:

Adverse reactions (WHO terminology)

Cetirizine

(n = 3260)

Placebo (n = 3061)

General disorders and disorders 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 drowsiness in the cetirizine group was higher than that of
in the placebo group, most cases of this adverse event were mild
or moderate severity. With an objective assessment carried out within the framework of
Other studies have 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, the following adverse reactions were observed with an incidence of 1% or greater in children aged 6 months to 12 years:

Adverse reactions (WHO terminology)

Cetirizine
(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 disorders 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-registration use of the drug.

Adverse events are presented below by MedDRA organ system class
and frequency of development, based on data from post-registration use
drug.

The incidence of adverse events was defined as follows: “uncommon” (≥ 1/1000, < 1/100); “rare” (≥ 1/10000, < 1/1000); "very rarely"
(< 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
consciousness, 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.

Violations of the organ of vision: 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: uncommon – diarrhea.

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

Disorders of the skin and subcutaneous tissues: infrequently – rash, itching;
rarely – urticaria; very rarely – angioedema, persistent drug-induced 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: uncommon – asthenia, malaise; rarely – peripheral edema.

Influence on the results of laboratory and instrumental studies: rarely
– increase in 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
If you notice any other side effects not listed in the instructions, please let us know
about this to the 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. According to in vitro tests, cetirizine does not interfere with the protein binding effect of warfarin.

Concomitant use of azithromycin, erythromycin, ketoconazole, theophylline and 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 patients took cetirizine,
who have previously received treatment with theophylline. However, pretreatment with cetirizine did not significantly affect 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, separate administration is recommended – glipizide in the morning and cetirizine in the evening.

The degree of absorption of cetirizine is not reduced by simultaneous food intake,
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%, whereas ritonavir exposure was not significantly 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 Renewal.

Overdose

Symptoms

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

Treatment

There is no specific antidote.

In case of overdose, symptomatic or supportive treatment is recommended.
treatment. 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

Update of PFC JSC, Russia