Cetirizine Reneval, 10 mg 30 pcs

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

ATX code: R06AE07

Pharmacological properties

Mechanism of action

Cetirizine, the active ingredient of Cetirizine Reneval, is a metabolite of hydroxyzine and has an antihistamine effect with antiallergic 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.

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 the 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

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The drug is rapidly absorbed from the gastrointestinal tract after oral administration. The pharmacokinetic parameters of cetirizine when administered in doses from 5 to
60 mg vary linearly. 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 receiving cetirizine
in dose of 10 mg maximum concentration (C_max) 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
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 administration of 10 mg in adults, total clearance of cetirizine is 0.60 ml/min/kg; the half-life (T_1/2) is approximately 10 hours. Administration of several
doses does not change the 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.

Separate patient groups

Elderly patients:

In 16 elderly individuals, the T_1/2 was 50% higher at a single dose of 10 mg, and the excretion rate was 40% lower 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 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.

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 T_1/2 lengthens 3-fold 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
10 or 20 mg 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 use of the drug is indicated in adults and children from 6 years to relieve:

Active ingredient

Composition

How to take, the dosage

Ingestion.

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

Cetirizine Reneval should not be chewed and it is recommended to drink water.

Cetirizine Reneval can be taken regardless of meals.

Adults: 10 mg (1 tablet) once daily.

Children

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 (½ tablet in the morning and evening).

Children over 12 years of age: 10 mg (1 tablet) once daily.

Sometimes an initial dose of 5 mg (½ 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.

Special patient groups

Patients with renal failure: since Cetirizine Reneval
is excreted mainly by the kidneys (see subsection “Pharmacokinetics”),
if no alternative treatment is available for patients with renal insufficiency, the drug dosing regimen should be adjusted depending on
renal function (CK values).

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 value obtained by a factor of 0.85.

Dosing in adult patients with renal impairment

Renal failure

CKR ml/min

Dosing regimen

Interaction

Simultaneous use with azithromycin, cimetidine, erythromycin, ketoconazole or pseudoephedrine does not affect the pharmacokinetic parameters of cetirizine. No pharmacokinetic interactions have been observed. According to in vitro trials, cetirizine does not affect the protein binding effect of warfarin.

The concomitant administration of azithromycin, erythromycin, ketoconazole, theophylline and pseudoephedrine showed no significant changes in clinical laboratory parameters, vital signs 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 7.7% and 6.4%, respectively
for cetirizine and theophylline. Simultaneously, cetirizine clearance decreased by -16%,
and by -10% for 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 (0.8%O) was not significantly enhanced 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 intakes 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 cetirizine administration.

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

Special Instructions

In patients with spinal cord injury, prostatic hyperplasia,
as well as 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 insufficiency, 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 is administered due to the fact that H1-histamine receptor blockers inhibit the development of cutaneous allergic reactions.

Cetirizine Reneval 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 appear,
even if these symptoms were absent at the beginning of treatment. In some cases,
symptoms may be intense and require resumption of cetirizine. The symptoms disappear when cetirizine is resumed.

Children

Cetirizine Reneval 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 for your own personal use and should not be given to others, as it can be harmful to them, even if you have the same symptoms as you do.

Influence on ability to drive, machinery

Cetirizine may cause increased drowsiness; therefore, Cetirizine Reneval may affect your ability to drive, machinery.

Synopsis

Contraindications

Cautious

Side effects

Data from clinical studies

Review

The results of clinical studies have demonstrated that the use of
cetirizine at recommended doses has resulted in the development of minor adverse effects on the CNS, 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, there have been
reported isolated cases of difficulty urinating, impaired accommodation and dry mouth.

Liver function abnormalities accompanied by increased
hepatic enzyme activity and bilirubin levels have been reported. In most cases the adverse events resolved after discontinuation of cetirizine.

List of adverse side effects

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

According to the pooled analysis, the following adverse reactions with an incidence of 1.0% or greater were identified in placebo-controlled studies when cetirizine was used at a dose of 10 mg

Indesirable reactions (WHO terminology)

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Cetirizine

(n = 3260)

Placebo (n = 3061)

General disorders and disorders at the point of administration

Tiredness

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1.63%

0.95%

Nervous system disorders

Dizziness

Headache

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1.10%

7.42%

0.98%

8.07%

Gastrointestinal tract disorders

Pain in the stomach

Dry mouth

Nausea

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0.98%

2.09%

1.07%

1.08 %

0.82 %

1.14 %

Mental disorders

Sleepiness

9.63%

5.00%

1.29%

1.34%

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
or moderate in severity. In objective evaluations conducted in
other studies, it was confirmed that the use of cetirizine at the recommended daily dose in healthy young volunteers did not affect their daily activity.

Children

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

Unwanted reactions (WHO terminology)

Cetirizine
(n = 1656)

Placebo (n = 1294)

Rhinitis

1.4%

1.1%

General and site violations

Fatigue

1.0%

0.3%

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,
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 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 the formation 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), pregnancy and childbirth.

In pregnancy, cetirizine may be prescribed after consultation with a physician if the anticipated 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 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. During breastfeeding, use after consultation with a physician if the anticipated benefit to the mother exceeds the potential risk to the baby.

Fertility

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

Before using the drug, if you are pregnant, or if you suspect that you might
be pregnant, or are planning to become pregnant, you should consult
your doctor.

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