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 adults and children from 6 months and older for relief:

Application in children from 6 to 12 months is possible only with the prescription of a doctor and under strict medical supervision.

Active ingredient

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 (methyl paraben), glacial acetic acid, propyl parahydroxybenzoate (propyl paraben), purified water

How to take, the dosage

Ingestion.

The drug should be taken in the evening, since the symptoms are more pronounced in the evening.

Cetirizine Reneval may be taken with a glass of water if necessary.

Cetirizine Reneval can be taken regardless of meals.

Adults: 10 mg (20 drops) once daily.

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

Children

Application in children from 6 to 12 months is only possible with a doctor’s prescription and under strict medical supervision!

Children 6 to 12 months: 2.5 mg (5 drops) once daily.

Children 1 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 daily.

Sometimes an initial dose of 5 mg (10 drops) 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 patient groups

Elderly patients

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

Patients with renal insufficiency

As the drug Cetirizine Reneval is eliminated from the body mainly by the kidneys
(see subsection “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 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 0.85.

Dosing in adult patients with renal impairment:

Renal failure

KKC (ml/min)

Dosing regimen

Norm

≥ 80

10 mg (20 drops) once daily

Mild

50-79

10 mg (20 drops) once daily

Medium

30-49

5 mg (10 drops) once daily

Severe

10-30

5 mg (10 drops) every other day

Terminal stage – patients on dialysis

< 10

drug administration is contraindicated

.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 improvement is not seen after treatment, or if new symptoms occur, you should talk to your doctor.

Consider the route of administration and dose only as directed.

Instructions for opening the bottle

The bottle has a first opening safety cap with child resistant protection. The bottle is opened 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 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 small 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%) 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 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 intake of cetirizine.

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

Special Instructions

Because of the potential central nervous system depressant effects, caution should be exercised when prescribing Cetirizine Reneval 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):

The drug contains the excipients methyl parahydroxybenzoate and propyl parahydroxybenzoate which may cause allergic reactions, including delayed type.

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 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 because H1-histamine receptor blockers inhibit the development of cutaneous allergic reactions.

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 ability to drive, machinery

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

Synopsis

Contraindications

Cautions

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 in a dose of 10 mg:

Unwanted reactions (WHO terminology).

Cetirizine

(n = 3260)

Placebo (n = 3061)

General and site disturbances

Fatigue

1.63%

0.95%

Nervous system disorders

Dizziness

Headache

1.10%

7.42%

0.98%

8.07%

Gastrointestinal disorders

Pain in the stomach

Dry mouth

Nausea

/p>

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, the following adverse reactions were found in children aged 6 months to 12 years with an incidence of 1% or higher:

Adverse reactions (WHO terminology)

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 ingestion of at least five times the recommended daily dose
included the following: confusion, diarrhea, fatigue, headache, malaise, mydriasis,
itching, anxiety, 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), the course of pregnancy and postnatal development.

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.

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

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

Prefer to your doctor.

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