Allergolik

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ALEGRGOLIK (ALERGOLIK)

Composition:

Active substance: levocetirizine dihydrochloride;

1 ml (25 drops) of solution contains levocetirizine dihydrochloride 5 mg;

Excipients: sodium acetate trihydrate; glacial acetic acid; propylene glycol; glycerol; sodium saccharin; methylparahydroxybenzoate (E 218); propylparahydroxybenzoate (E 216); purified water.

Pharmaceutical form. Oral drops, solution.

Main physicochemical properties: clear, colorless or almost colorless solution.

Pharmacotherapeutic group. Antihistamines for systemic use. Piperazine derivatives. Levocetirizine. ATC code R06A E09.

Pharmacological properties.

Pharmacodynamics.

Levocetirizine is the active, stable R-enantiomer of cetirizine and belongs to the group of competitive histamine antagonists. Its pharmacological action is due to blockade of H₁-histamine receptors. The affinity of levocetirizine for H₁-histamine receptors is twice as high as that of cetirizine. It affects the histamine-dependent phase of allergic reactions, reduces eosinophil migration, vascular permeability, and limits the release of inflammatory mediators. It prevents the development and alleviates the course of allergic reactions, exerts anti-exudative, antipruritic, and anti-inflammatory effects, and has almost no anticholinergic or anti-serotonin activity.

Pharmacokinetics.

The pharmacokinetic parameters of levocetirizine are linear and are almost identical to those of cetirizine.

Absorption. After oral administration, the drug is rapidly and extensively absorbed. The extent of absorption is independent of dose and is not altered by food intake; however, the maximum plasma concentration (C_max) is reduced and reached later. Bioavailability reaches 100%.

The onset of action occurs within 12 minutes after a single dose in 50% of patients and within 0.5–1 hour in 95% of patients. C_max in blood plasma is achieved within 50 minutes after a single therapeutic dose. Steady-state plasma concentration is reached after 2 days of continuous dosing. C_max is 270 ng/mL after a single dose and 308 ng/mL after repeated dosing at 5 mg, respectively.

Distribution. There is no available information on tissue distribution of the drug in humans or on the ability of levocetirizine to cross the blood-brain barrier. In animal studies, the highest concentrations were observed in the liver and kidneys, while the lowest were found in tissues of the central nervous system (CNS). The volume of distribution is 0.4 L/kg. Plasma protein binding is 90%.

Metabolism. Approximately 14% of levocetirizine undergoes metabolism in the human body. The metabolic process includes oxidation, N- and O-dealkylation, and conjugation with taurine. Dealkylation primarily involves the cytochrome CYP3A4, whereas oxidation involves multiple and/or undefined CYP isoenzymes. Levocetirizine does not affect the activity of cytochrome isoenzymes 1A2, 2C9, 2C19, 2D6, 2E1, and 3A4 at concentrations significantly exceeding those achieved after oral administration of a 5 mg dose. Due to the low extent of metabolism and lack of inhibitory potential, drug interactions between levocetirizine and other substances (and vice versa) are unlikely.

Elimination. The drug is primarily eliminated via glomerular filtration and active tubular secretion. The elimination half-life (T_½) in adults is 7.9 ± 1.9 hours. The elimination half-life is shorter in young children. Total body clearance in adults is 0.63 mL/min/kg. Elimination of levocetirizine and its metabolites occurs mainly via urine (on average, 85.4% of the administered dose is excreted). Only 12.9% of the administered dose is excreted in feces.

Total clearance of levocetirizine correlates with creatinine clearance. Therefore, dosing intervals of levocetirizine should be adjusted according to creatinine clearance in patients with moderate to severe renal impairment. In end-stage renal disease with anuria, total clearance of levocetirizine is reduced by approximately 80% compared to individuals without such impairment. The amount of levocetirizine removed during a standard 4-hour hemodialysis session is less than 10%.

Clinical characteristics.

Indications.

Symptomatic treatment of allergic rhinitis (including perennial allergic rhinitis) and urticaria.

Contraindications.

Hypersensitivity to levocetirizine or to any other component of the medicinal product, or to any piperazine derivatives.

Severe form of chronic renal insufficiency (creatinine clearance < 10 ml/min).

Interaction with other medicinal products and other forms of interaction.

Studies on interactions with levocetirizine have not been conducted. Studies with cetirizine (racemic mixture) have shown that concomitant administration with antipyrine, pseudoephedrine, cimetidine, ketoconazole, erythromycin, azithromycin, glipizide, or diazepam does not result in clinically significant adverse interactions. Concomitant administration with theophylline (400 mg/day) reduces the total clearance of cetirizine by 16%, while the kinetics of theophylline remain unchanged. In a study of multiple-dose administration of ritonavir (600 mg twice daily) and cetirizine (10 mg daily), exposure to cetirizine increased by approximately 40%, whereas the distribution of ritonavir was slightly altered (-11%) with concomitant cetirizine administration.

Food intake does not affect the extent of absorption of the drug, but reduces the rate of its absorption.

Concomitant administration of cetirizine or levocetirizine with alcohol or other CNS depressants in sensitive patients may cause additional impairment of attention and ability to perform tasks.

Special precautions for use

Use with caution in patients with chronic renal insufficiency (dose adjustment required) and in elderly patients with renal impairment (possible reduction in glomerular filtration rate). Alcohol consumption should be avoided during treatment (see section "Interaction with other medicinal products and other forms of interaction").

When prescribing the drug to patients with factors predisposing to urinary retention (e.g., spinal cord injury, benign prostatic hyperplasia), it should be taken into account that levocetirizine may increase the risk of urinary retention.

Levocetirizine should be used with caution in patients with epilepsy or at risk of seizures, as its use may lead to exacerbation of seizures.

Antihistamines suppress the response to skin allergy tests; therefore, the drug should be discontinued at least 3 days before testing (elimination period).

Pruritus may occur after discontinuation of levocetirizine, even if this symptom was not present before treatment initiation. The symptom may resolve spontaneously. In some cases, the symptom may be intense and re-initiation of treatment may be required. The symptom should resolve after restarting therapy.

The presence of methylparahydroxybenzoate (E 218) and propylparahydroxybenzoate (E 216) may cause allergic reactions (possibly delayed).

Use during pregnancy or breastfeeding

Levocetirizine is contraindicated during pregnancy. Levocetirizine passes into breast milk; therefore, breastfeeding should be discontinued if treatment with the drug is necessary.

Fertility

There are no clinical data (including animal studies) on the effect of levocetirizine on fertility.

Ability to affect reaction speed when driving or operating machinery

Driving vehicles or operating machinery should be avoided during treatment with this medicinal product.

Method of administration and dosage.

The medication should be administered orally to adults and children aged 2 years and older, regardless of food intake. The drops may be diluted in a small amount of water. If dilution is used, especially when administering to children, care should be taken to ensure that the volume of water in which the drops are dissolved corresponds to the amount of liquid the patient can swallow. The diluted solution should be taken immediately.

Recommended doses:

• Children aged 2 to 6 years: the recommended daily dose is 2.5 mg (12 drops). This dose should be administered as 1.25 mg (6 drops) twice daily;
• Children aged 6 to 12 years: the recommended daily dose is 5 mg (25 drops) once daily;
• Children aged 12 years and older, and adults: the recommended daily dose is 5 mg (25 drops) once daily.

Dose adjustment is not required for elderly patients with normal renal function. For patients with impaired renal function, dosage must be adjusted according to creatinine clearance as specified in the table.

To use this dosing table, the patient's creatinine clearance (CrCl) in mL/min must be estimated. CrCl (mL/min) should be estimated from serum creatinine concentration (mg/dL) using the following formula:

Dosage adjustment of the drug in patients with impaired renal function

For children with impaired kidney function, the dose of the drug should be individually adjusted based on renal clearance and body weight.

No dosage adjustment is required for patients with hepatic impairment alone. For patients with both hepatic and renal impairment, adjust the dosage regimen according to the table above.

Duration of use: Patients with intermittent allergic rhinitis (disease symptoms lasting < 4 days per week or for less than 4 weeks) should be treated according to the condition and medical history; treatment may be discontinued if symptoms resolve and restarted upon recurrence of symptoms. For persistent allergic rhinitis (disease symptoms lasting > 4 days per week and for more than 4 weeks), during the allergen exposure period, continuous therapy may be considered. For chronic conditions (chronic allergic rhinitis, chronic urticaria), the treatment duration may last up to 1 year (data available from clinical studies using the racemate).

Children.

The use of levocetirizine in children under 2 years of age is not recommended due to limited data in this age group.

The drug may be used in children aged 2 years and older.

Overdose.

Symptoms: In adults, overdose may be associated with drowsiness; in children, initial excitation and increased irritability followed by drowsiness.

Treatment. There is no specific antidote for levocetirizine. In case of overdose symptoms, symptomatic and supportive treatment is recommended. Gastric lavage should be considered shortly after drug ingestion. Hemodialysis is not effective for removing levocetirizine from the body.

Adverse reactions.

Immune system disorders: hypersensitivity, including anaphylaxis.

Nutrition and metabolism disorders: increased appetite.

Nervous system disorders: somnolence, headache, fatigue, weakness, asthenia, convulsions, paraesthesia, dizziness, loss of consciousness, tremor, dysgeusia.

Psychiatric disorders: sleep disorders, excitation, hallucinations, depression, aggression, insomnia, suicidal thoughts, nightmares.

Cardiac disorders: palpitations, tachycardia.

Eye disorders: visual disturbances, blurred vision, nystagmus.

Ear and labyrinth disorders: vertigo.

Hepatobiliary disorders: hepatitis.

Renal and urinary disorders: dysuria, urinary retention.

Respiratory, thoracic and mediastinal disorders: dyspnoea.

Gastrointestinal disorders: diarrhoea, vomiting, constipation, dry mouth, nausea, abdominal pain.

Skin and subcutaneous tissue disorders: angioneurotic oedema, fixed drug eruptions, pruritus, rash, urticaria.

Musculoskeletal, connective tissue and bone disorders: myalgia, arthralgia.

General disorders: oedema.

Investigations: weight increase, abnormal liver function tests.

Description of selected adverse reactions

Pruritus has been reported after discontinuation of levocetirizine.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after medicine authorization is important. It allows continued monitoring of the benefit-risk balance of the medicine. Healthcare professionals are encouraged to report any suspected adverse reactions.

Shelf life. 2 years.

After opening the bottle, use within 3 months.

Storage conditions.

Store in the original packaging at a temperature not exceeding 30°C. Keep out of reach of children.

Packaging.

10 ml in a bottle with dropper cap. 1 bottle per cardboard pack.

Availability.

Over-the-counter.

Manufacturer.

JSC "Tekhnolohiya".

Manufacturer's address and place of business.

8 Stara Prorynna Street, Uman, Cherkasy region, 20300, Ukraine.