Allergolik

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

Composition:

Active substance: levocetirizine dihydrochloride;

1 tablet contains levocetirizine dihydrochloride 5 mg;

Excipients: microcrystalline cellulose, colloidal anhydrous silicon dioxide, lactose monohydrate, magnesium stearate, hypromellose (hydroxypropylmethylcellulose), polyethylene glycol 400 (macrogol 400), titanium dioxide (E 171).

Pharmaceutical form. Film-coated tablets.

Main physico-chemical properties: round, film-coated tablets, white or almost white, with convex upper and lower surfaces. When broken and viewed under a magnifying glass, a core surrounded by a single continuous layer is visible.

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 effect is due to blockade of H1-histamine receptors. The affinity of levocetirizine for H1-histamine receptors is twice 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, exerting anti-exudative, anti-pruritic, and anti-inflammatory effects, with minimal anticholinergic and anti-serotonin activity.

Pharmacokinetics

The pharmacokinetic parameters of levocetirizine are linear and do not significantly differ from those of cetirizine.

Absorption. Levocetirizine is rapidly absorbed after oral administration. Food intake does not affect the extent of absorption but reduces its rate. Bioavailability reaches 100%.

In 50% of patients, the effect of the drug develops within 12 minutes after a single dose, and in 95% – within 0.5–1 hour. C_max in blood plasma is achieved within 50 minutes after a single oral therapeutic dose. Steady-state plasma concentration is reached after 2 days of continuous drug administration. C_max is 270 ng/mL after a single dose and 308 ng/mL after repeated administration of a 5 mg dose.

Distribution. There is no available information regarding the distribution of the drug in human tissues or its penetration through the blood-brain barrier. In animal studies, the highest concentrations were observed in the liver and kidneys, while the lowest were found in central nervous system tissues. The volume of distribution is 0.4 L/kg. Plasma protein binding is 90%.

Biological transformation. Approximately 14% of levocetirizine is metabolized in the human body. The metabolic process includes oxidation, N- and O-dealkylation, and conjugation with taurine. Dealkylation primarily involves cytochrome CYP3A4, while oxidation involves numerous and/or undefined CYP isoforms. Levocetirizine does not affect the activity of cytochrome isoenzymes 1A2, 2C9, 2C19, 2D6, 2E1, and 3A4 at concentrations significantly exceeding the maximum levels achieved after a 5 mg oral 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. Drug excretion occurs mainly via glomerular filtration and active tubular secretion. The elimination half-life (T_1/2) in adults is 7.9 + 1.9 hours. The T_1/2 is shorter in children. Total clearance in adults is 0.63 mL/min/kg. Levocetirizine and its metabolites are primarily excreted via urine (on average, 85.4% of the administered dose is excreted). Only 12.9% of the administered dose is excreted in feces.

In patients with impaired renal function (creatinine clearance < 40 mL/min), drug clearance is reduced and T_1/2 is prolonged (in patients undergoing hemodialysis, total clearance is reduced by 80%), necessitating appropriate dose adjustment. The amount of levocetirizine removed during a standard 4-hour hemodialysis session is < 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).

Rare hereditary disorders of galactose intolerance, lactase deficiency, or glucose-galactose malabsorption.

Interaction with other medicinal products and other forms of interaction.

Interaction studies with levocetirizine have not been conducted. Studies with cetirizine (racemate compound) showed that concomitant administration with antipyrine, pseudoephedrine, cimetidine, ketoconazole, erythromycin, azithromycin, glipizide, or diazepam does not reveal clinically significant adverse interactions. Concomitant use with theophylline (400 mg per day) reduces total cetirizine clearance by 16% (theophylline kinetics remain unchanged). In a study of multiple dosing of ritonavir (600 mg twice daily) and cetirizine (10 mg daily), cetirizine exposure increased by approximately 40%, while ritonavir distribution decreased by 11% compared to administration without concurrent cetirizine. There are no data on potentiation of sedative effects when used at therapeutic doses. However, concomitant use of sedatives should be avoided during treatment with this medicinal product.

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

Concomitant use of cetirizine or levocetirizine with alcohol or other central nervous system depressants in sensitive patients may cause additional reduction in 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 insufficiency (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 injuries, benign prostatic hyperplasia), it should be borne in mind 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 increased seizure activity.

Antihistamines suppress the response to skin allergy tests; therefore, treatment should be discontinued at least 3 days prior to 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, it may be intense and require reinitiation of treatment. The symptom should resolve after restarting therapy.

The tablet formulation should not be administered to children under 6 years of age, as this dosage form does not allow appropriate dose adjustment. Pediatric patients in this age group should be prescribed levocetirizine in a pharmaceutical form suitable for pediatric use.

If an established intolerance to certain sugars exists, consult a physician before using this medicinal product.

Use during pregnancy or breastfeeding

Levocetirizine is contraindicated during pregnancy. Cetirizine passes into breast milk; therefore, breastfeeding should be discontinued if treatment with this medicinal product is required.

Fertility

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

Ability to influence reaction speed when driving or operating machinery

Patients should refrain from driving vehicles or operating machinery during treatment with this medicinal product.

Dosage and Administration

The drug is intended for oral administration to adults and children aged 6 years and older at a daily dose of 5 mg once daily. The tablet should be taken regardless of food intake. Swallow the tablet whole with a small amount of water.

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 (see below).

To adjust dosing, the patient's creatinine clearance (CLcr) in milliliters per minute must be assessed. CLcr (mL/min) should be calculated based on serum creatinine concentration (mg/dL) using the following formula:

Dosage adjustment of the drug for patients with renal function impairment

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

Dose adjustment is not required for patients with isolated hepatic impairment. For patients with both hepatic and renal impairment, adjust the dosage regimen according to the table above.

Duration of treatment: For patients with intermittent allergic rhinitis (duration of disease symptoms < 4 days per week or for less than 4 weeks), treatment duration depends on the disease and medical history; treatment may be discontinued if symptoms resolve and resumed upon recurrence of symptoms. For persistent allergic rhinitis (duration of disease symptoms > 4 days per week and for more than 4 weeks) during periods of allergen exposure, continuous therapy may be recommended. For chronic conditions (chronic allergic rhinitis, chronic urticaria), treatment duration may last up to 1 year (data are available from clinical studies using the racemate).

Children.

The tablet formulation should not be used in children under 6 years of age, as this dosage form does not allow for appropriate dose adjustment. This patient group is recommended to receive levocetirizine in another pharmaceutical form.

Overdose.

Symptoms: drowsiness in adults; agitation, increased irritability alternating with drowsiness, in children.

Treatment. There is no specific antidote for levocetirizine. In case of overdose symptoms, symptomatic and supportive therapy is recommended. Gastric lavage should be considered shortly after drug intake. 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, increased fatigue, weakness, asthenia, seizures, 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: increased body weight, 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 marketing authorization is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are encouraged to report any suspected adverse reactions.

Shelf life. 3 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25°C. Keep out of reach of children.

Packaging.

10 tablets in a blister. 1, 2 or 3 blisters in a cardboard carton.

Supply category.

Over-the-counter.

Manufacturer.

JSC "Tekhnolog".

Manufacturer's address and place of business.

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