Xyzal^® (Drops) Instructions for Use

Marketing Authorization Holder

UCB Farchim, S.A. (Switzerland)

Manufactured By

Aesica Pharmaceuticals, S.r.l. (Italy)

Or

UCB Farchim, S.A. (Switzerland)

Packaging and Quality Control Release

AESICA Pharmaceuticals, S.r.l. (Italy)

Contact Information

UCB Pharma S.A. (Belgium)

ATC Code

R06AE09 (Levocetirizine)

Active Substance

Levocetirizine (Rec.INN registered by WHO)

Dosage Forms

Xyzal®		Oral drops 5 mg/1 ml: 10 ml or 20 ml bottle 1 pc.
		Film-coated tablets 5 mg: 7, 10, 14 or 20 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets from white to almost white, oval, biconvex; with the logo “Y” on one side.

Excipients: lactose monohydrate, microcrystalline cellulose (Avicel PH-102), colloidal silicon dioxide, magnesium stearate; film coat: Opadry Y-1-7000 (contains hypromellose, titanium dioxide (E171), macrogol 400).

7 pcs. – blisters (1) – cardboard packs.
7 pcs. – blisters (2) – cardboard packs.
10 pcs. – blisters (1) – cardboard packs.
10 pcs. – blisters (2) – cardboard packs.

Oral drops in the form of an almost colorless, slightly opalescent solution.

Excipients: sodium acetate, acetic acid, propylene glycol, glycerol 85%, methylparaben, propylparaben, sodium saccharin, purified water.

10 ml – dark glass bottles with a dropper (1) – cardboard packs.
20 ml – dark glass bottles with a dropper (1) – cardboard packs.

Clinical-Pharmacological Group

Histamine H₁-receptor blocker. Antiallergic drug

Pharmacotherapeutic Group

Systemic antihistamines, piperazine derivatives

Pharmacological Action

Histamine H₁-receptor blocker, an enantiomer of cetirizine, belongs to the group of competitive histamine antagonists. The affinity for histamine H₁-receptors of levocetirizine is 2 times higher than that of cetirizine.

Levocetirizine affects the histamine-dependent stage of allergic reactions, and also reduces eosinophil migration, reduces vascular permeability, and limits the release of inflammatory mediators. It prevents the development and alleviates the course of allergic reactions, has anti-exudative, antipruritic effects, and has practically no anticholinergic and antiserotonin effects. In therapeutic doses, it has practically no sedative effect.

Pharmacokinetics

Absorption

The pharmacokinetic parameters of levocetirizine change linearly and are practically the same as the pharmacokinetics of cetirizine. After oral administration, Levocetirizine is rapidly absorbed from the gastrointestinal tract. Food intake does not affect the extent of absorption, although its rate decreases. After a single oral administration at a therapeutic dose, C_max in blood plasma in adults is reached after 0.9 hours and is 207 ng/ml, after repeated administration at a dose of 5 mg/day – 308 ng/ml. Bioavailability is 100%.

Distribution

C_ss is reached after 2 days. The binding of levocetirizine to plasma proteins is 90%.
V_d is 0.4 l/kg.

Metabolism

Less than 14% is metabolized in the liver by N- and O-dealkylation (unlike other histamine H₁-receptor blockers, which are metabolized in the liver with the participation of cytochrome P450 isoenzymes) to form a pharmacologically inactive metabolite. Due to the low level of metabolism and the absence of metabolic potential, the interaction of levocetirizine with other drugs seems unlikely.

Excretion

In adults, it is 7.9±1.9 hours, total clearance is 0.63 ml/min/kg. About 85.4% of the dose is excreted by the kidneys unchanged by glomerular filtration and tubular secretion; about 12.9% is excreted through the intestines.

Pharmacokinetics in special clinical cases

In patients with renal failure (creatinine clearance less than 40 ml/min), the clearance of levocetirizine decreases, and T_1/2 increases (in patients on hemodialysis, total clearance decreases by 80%), which requires an appropriate change in the dosage regimen. Less than 10% of levocetirizine is removed during a standard 4-hour hemodialysis procedure.

In young children, T_1/2 is shortened.

Indications

Symptomatic treatment of allergic diseases and conditions

• Perennial (persistent) and seasonal (intermittent) allergic rhinitis and allergic conjunctivitis (itching, sneezing, rhinorrhea, lacrimation, conjunctival hyperemia, nasal congestion);
• Hay fever (pollinosis);
• Urticaria (including chronic idiopathic urticaria);
• Angioedema (Quincke’s edema);
• Other allergic dermatoses accompanied by itching and rashes.

ICD codes

Dosage Regimen

The drug is prescribed orally during meals or on an empty stomach.

The tablets are taken with a small amount of water, without chewing.

The oral drops are taken with a teaspoon. If necessary, the dose of the drug can be diluted in a small amount of water immediately before use.

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

Children aged 2 to 6 years 1.25 mg (5 drops) 2 times/day; daily dose – 2.5 mg (10 drops).

Since Levocetirizine is excreted by the kidneys, when prescribing the drug to elderly patients and patients with renal failure, the dose should be adjusted depending on the creatinine clearance value.

Creatinine clearance can be calculated based on serum creatinine concentration using the following formula.

For men

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

For women obtained value × 0.85

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

For patients with impaired liver function only, no dose adjustment is required.

The duration of use depends on the indications. The course of treatment for hay fever averages 1-6 weeks. For chronic diseases (perennial rhinitis, atopic dermatitis), the duration of treatment can be increased to 18 months.

Adverse Reactions

Possible side effects are listed below by body system and frequency of occurrence: common (≥1/10); uncommon (from ≥1/100 to <1/10); rare (from ≥1/1000 to <1/100); very rare (from ≥1/10,000 to < 1/1000).

From the nervous system uncommon – headache, fatigue, drowsiness; rare – asthenia; very rare – aggression, agitation, convulsions, hallucinations, depression, visual impairment.

From the cardiovascular system very rare – tachycardia.

From the respiratory system very rare – dyspnea.

From the digestive system uncommon – dry mouth; rare – abdominal pain; very rare – nausea, diarrhea, hepatitis, changes in liver function tests.

From the musculoskeletal system very rare – myalgia.

From metabolism very rare – weight gain.

Allergic reactions very rare – itching, rash, urticaria, angioedema, anaphylaxis.

Contraindications

• End-stage renal failure (CrCl less than 10 ml/min);
• Children under 6 years of age (for tablets);
• Children under 2 years of age (for oral drops);
• Pregnancy;
• Hypersensitivity to the components of the drug, especially in patients with galactosemia or severe lactose intolerance (for tablets);
• Hypersensitivity to levocetirizine or piperazine derivatives.

With caution the drug should be used in chronic renal failure (dose adjustment required), in elderly patients (with age-related decrease in glomerular filtration).

Use in Pregnancy and Lactation

There have been no adequate and well-controlled clinical studies on the safety of the drug in pregnant women, so Xyzal^® should not be prescribed during pregnancy.

Levocetirizine is excreted in breast milk, so if it is necessary to use the drug during lactation, breastfeeding should be discontinued during the period of use.

In experimental studies in animals, no direct or indirect adverse effects of levocetirizine on the developing fetus (including in the postnatal period) were identified, and the course of pregnancy and childbirth also did not change.

Use in Hepatic Impairment

No dose adjustment is required for patients with hepatic impairment.

Use in Renal Impairment

Contraindicated in end-stage renal failure (CrCl less than 10 ml/min).

For patients with chronic renal failure with CrCl 49-30 ml/min, the dose is reduced by 2 times (1 tablet every other day), with CrCl 29-10 ml/min, the dose is reduced by 3 times (1 tablet once every 3 days).

Pediatric Use

Contraindicated in children under 6 years of age (for tablets); in children under 2 years of age (for oral drops).

Children over 6 years: daily dose 5 mg (1 tablet or 20 drops).

Children aged 2 to 6 years 1.25 mg (5 drops) 2 times/day; daily dose – 2.5 mg (10 drops).

Geriatric Use

Since Levocetirizine is excreted by the kidneys, when prescribing the drug to elderly patients, the dose should be adjusted depending on the creatinine clearance value.

Special Precautions

Patients should exercise caution when taking the drug and simultaneously consuming alcohol.

Effect on ability to drive vehicles and operate machinery

Objective assessment of the ability to drive vehicles and operate machinery did not reliably reveal any adverse events when prescribing the drug at the recommended dose. Nevertheless, during the treatment period, it is advisable to refrain from engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

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

Treatment immediately after taking the drug, perform gastric lavage or induce artificial vomiting. It is recommended to prescribe activated charcoal, carry out symptomatic and supportive therapy. There is no specific antidote. Hemodialysis is ineffective.

Drug Interactions

Studies of the interaction of levocetirizine with other drugs have not been conducted.

When studying the drug interaction of the cetirizine racemate with pseudoephedrine, cimetidine, ketoconazole, erythromycin, azithromycin, glipizide and diazepam, no clinically significant undesirable interaction was found.

With simultaneous use with theophylline (400 mg/day), the total clearance of cetirizine decreases by 16%, the pharmacokinetic parameters of theophylline do not change.

In some cases, with simultaneous use of levocetirizine with ethanol or drugs that have a depressant effect on the central nervous system, their effect on the central nervous system may be enhanced, although it has been proven that the cetirizine racemate potentiates the effect of alcohol.

Storage Conditions

Tablets should be stored out of the reach of children at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 4 years.

Oral drops should be stored out of the reach of children, protected from light, at a temperature not exceeding 30°C (86°F). Shelf life – 3 years. After opening the bottle, the shelf life is 3 months.

Dispensing Status

The drug Xyzal^® oral drops are dispensed by prescription.
The drug Xyzal^® tablets are dispensed without a prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.