Xizal, drops 5 mg/ml 10 ml

Anti-allergic agent -H1-histamine receptor blocker.

ATC code: R06AE08.

Pharmacological properties

Pharmacodynamics. Levocetirizine – the active substance of Xizal® is R-enantiomer of cetirizine, which belongs to the group of competitive histamine antagonists and blocks H1-histamine receptors. Levocetirizine has twice the affinity to H1-receptors as cetirizine.

Levocetirizine influences the histamine-dependent stage of allergic reactions, also reduces migration of eosinophils, decreases vascular permeability and limits the release of inflammatory mediators. Levocetirizine prevents the development and facilitates the course of allergic reactions, has antiexudative, antipruritic action, it has practically no anticholinergic and antiserotonin action. In therapeutic doses it has practically no sedative effect.

Pharmacokinetics. Pharmacokinetic parameters of levocetirizine change linearly and practically do not differ from the pharmacokinetics of cetirizine. Absorption. After oral administration, the drug is quickly and completely absorbed from the gastrointestinal tract. Food intake does not affect the completeness of absorption, although its rate is reduced.

In adults after a single therapeutic dose (5 mg) the maximum concentration (Cmax) in plasma is reached after 0.9 h and is 270 ng/ml, after re-administration of 5 mg/day – 308 ng/ml. Permanent level of concentration is reached after 2 days. Distribution. Levocetirizine is 90% bound to plasma proteins. Volume of distribution (Vd) is 0.4 l/kg. Bioavailability reaches 100%.

Metabolism. In small amounts (< 14 %) it is metabolized in the body by N- and O-dealkylation (unlike other Hg histamine receptor antagonists, which are metabolized in the liver via the cytochrome system) to form a pharmacologically inactive metabolite. Due to the low level of metabolism and lack of metabolic potential, interaction of levocetirizine with other drugs seems unlikely.

Elimation. In adults the elimination half-life (Tsh) is (7.9 ± 1.9) h; in young children the T 1/2 is shorter. In adults, the total clearance is 0.63 ml/min/kg. About 85.4% of the administered dose of the drug is excreted unchanged by the kidneys through tubular filtration and tubular secretion; about 12.9% – through the intestine.

In patients with renal insufficiency (creatinine clearance (CK) < 40 ml/min) the drug clearance decreases and Tc prolongs (thus, in patients on hemodialysis the total clearance decreases by 80%), which requires appropriate changes in dosing regimen. Less than 10% of levocetirizine is removed during a standard 4-hour hemodialysis procedure.

Indications

Symptomatic therapy of allergic diseases and conditions:

Active ingredient

Composition

1 ml contains:

The active ingredient:

levocetirizine dihydrochloride 5 mg.

Associates:

sodium acetate, acetic acid,

propylene glycol,

glycerol 85%,

methylparahydroxybenzoate,

propylparahydroxybenzoate,

sodium saccharinate,

purified water.

How to take, the dosage

The drug is taken orally with meals or on an empty stomach.

The oral drops are taken by teaspoonful. If necessary, the dose may be diluted in a small amount of water immediately before drinking.

Adults and children over 6 years: A daily dose of 5 mg (1 tablet or 20 drops).

Children 2 to 6 years of age: 1.25 mg (5 drops) 2 times daily; daily dose is 2.5 mg (10 drops).

Because levocetirizine is excreted by the kidneys, the dose should be adjusted according to the CK levels when prescribing in elderly patients and patients with renal impairment.

The CK can be calculated based on serum creatinine concentration using the following formula.

For men:

CK (ml/min)= [140-age (years)] × body weight (kg)/72 × serum creatinine (mg/dL)

For women: the resulting value × 0.85

Renal failureKKK(ml/min)Dose and frequency of administrationNorma>805 mg/dayMild degree50-795 mg/dayModerate degree30-495 mg/day once every 2 daysSevere degree< 305 mg/d once every 3 daysTerminal stage (patients on hemodialysis)<10The drug is contraindicated

For patients with renal and hepatic impairment, dosing is according to the table above.

Patients with hepatic impairment only do not require dosing adjustments.

The duration of treatment depends on the indication. The course of treatment of pollinosis is about 1-6 weeks. In case of chronic diseases (year-round rhinitis and atopic dermatitis) the duration of treatment may be increased up to 18 months.

Interaction

The study of interaction of levocetirizine with other medicinal products has not been conducted.

In the study of drug interactions of cetirizine racemate with pseudoephedrine, cimetidine, ketoconazole, erythromycin, azithromycin, glipizide and diazepam no clinically significant adverse interactions were found.

Concomitant administration with theophylline (400 mg/day) decreases total clearance of cetirizine by 16% (the kinetics of theophylline does not change).

In some cases, concomitant use of levocetirizine with alcohol or CNS depressant drugs may increase their effects on the CNS, although it has not been proven that cetirizine racemate potentiates the effect of alcohol.

Special Instructions

Caution is required for concomitant use with alcohol (see Interaction with other medicinal products).

Impact on driving and operating ability

An objective assessment of driving and operating ability has not reliably revealed any adverse events when taking the drug in the recommended dose. Nevertheless, during the use of the drug it is reasonable to refrain from potentially hazardous activities requiring high concentration and quick psychomotor reactions.

Contraindications

Side effects

Possible side effects are listed below by body system and frequency of occurrence: frequently (≥1/10); infrequently (≥1/100 to < 1/10); rarely (≥1/1000 to < 1/100); very rarely (≥1/10 000 to < 1/1000).

CNS disorders: infrequent – headache, fatigue, somnolence; rare – asthenia; very rare – aggression, agitation, seizures, hallucinations, depression, visual impairment.

Cardiovascular system disorders: very rarely – tachycardia.

Respiratory system disorders: very rare – dyspnea.

The digestive system: infrequent – dry mouth; rarely – abdominal pain; very rare – nausea, diarrhea, hepatitis, changes in liver function tests.

Muscular system: very rarely – myalgia.

Metabolism: very rare – weight gain.

Allergic reactions: very rarely – itching, rash, urticaria, angioedema, anaphylaxis.

Overdose

Symptoms: drowsiness (in adults), agitation and restlessness, followed by drowsiness (in children).

Treatment: immediately after ingestion of the drug it is necessary to flush the stomach or induce artificial vomiting.

The administration of activated charcoal, symptomatic and supportive therapy is recommended.

There is no specific antidote.

Hemodialysis is not effective.

Pregnancy use

Experimental studies on animals did not reveal any direct or indirect adverse effects of levocetirizine on the developing fetus, as well as on the development in the postnatal period; the course of pregnancy and childbirth was not changed either.

There have been no adequate and strictly controlled clinical studies on the safety of the drug during pregnancy, so levocetirizine should not be prescribed during pregnancy.

Levocetirizine is excreted with breast milk, so it should only be used if the estimated benefit to the mother exceeds the potential risk to the baby.

Similarities