Sezoniy

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT SEZONIA (SEZONIA)

Composition:

Active substance: levocetirizine;

One film-coated tablet contains levocetirizine dihydrochloride equivalent to 100% substance 5 mg;

Excipients: microcrystalline cellulose; lactose monohydrate; colloidal anhydrous silicon dioxide; magnesium stearate; coating: hypromellose; polyethylene glycol 6000; titanium dioxide (E 171).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: white or almost white, round, biconvex film-coated tablets.

Pharmacotherapeutic group.

Antihistamines for systemic use. Piperazine derivatives.

ATC code R06AE09.

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 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, exerting anti-exudative, anti-pruritic, and anti-inflammatory effects, with minimal anticholinergic and anti-serotonin activity.

Pharmacokinetics.

Pharmacokinetic parameters of levocetirizine exhibit linear kinetics, are independent of dose and time, and demonstrate low inter-patient variability. The pharmacokinetic profile after administration of a single enantiomer is the same as that observed with cetirizine. No chiral inversion occurs during absorption or elimination.

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

In 50% of patients, the drug's effect begins within 12 minutes after a single dose, and in 95% of patients, within 0.5–1 hour. Cmax in blood plasma is achieved within 50 minutes after a single oral therapeutic dose. Steady-state plasma concentration is reached after two days of regular dosing. Cmax is 270 ng/mL after a single dose and 308 ng/mL after repeated administration of 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. The volume of distribution is 0.4 L/kg. Plasma protein binding in humans is 90%.

Metabolism. In humans, the extent of metabolism is less than 14% of the dose; therefore, differences due to genetic polymorphism or concomitant use of enzyme inhibitors are expected to be negligible. The metabolic process includes aromatic oxidation, N- and O-dealkylation, and conjugation with taurine. Dealkylation primarily involves cytochrome CYP3A4, while aromatic oxidation involves multiple and/or undefined CYP isoforms. Levocetirizine does not affect the activity of cytochrome P450 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. Levocetirizine is eliminated via two pathways: glomerular filtration and active tubular secretion. The elimination half-life (T1/2) of levocetirizine in plasma in adults is 7.9+1.9 hours. T1/2 of levocetirizine is shorter in young children. The mean apparent total clearance in adults is 0.63 mL/min/kg. Levocetirizine and its metabolites are primarily excreted in urine (on average, 85.4% of the administered dose). Only 12.9% of the administered dose is excreted in feces.

Special populations

Renal impairment

The apparent clearance of levocetirizine correlates with creatinine clearance. Therefore, in patients with moderate to severe renal impairment, the dosing intervals of levocetirizine should be adjusted based on creatinine clearance. In anuric patients with end-stage renal disease, total clearance is reduced by approximately 80% compared to individuals with normal renal function. 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, cetirizine, hydroxyzine, to any other piperazine derivatives, or to any of the excipients of the medicinal product.

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

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

Pregnancy or breastfeeding.

Interaction with other medicinal products and other forms of interaction.

Interaction studies (including studies on CYP3A4 enzymes) with levocetirizine have not been conducted. Interaction studies with cetirizine (the racemate compound) showed that concomitant administration with antipyrine, azithromycin, cimetidine, diazepam, erythromycin, glipizide, ketoconazole, or pseudoephedrine does not cause clinically significant adverse interactions. When administered together with theophylline (400 mg per day), a slight decrease (by 16%) in total levocetirizine clearance was observed (theophylline distribution was not altered). In a study of multiple dosing of ritonavir (600 mg twice daily) and cetirizine (10 mg daily), the exposure to cetirizine increased by approximately 40%, while ritonavir distribution was slightly altered (-11%) compared to cetirizine co-administration.

There are no data regarding 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 concomitant food intake reduces the rate of absorption.

Concomitant use of cetirizine or levocetirizine with alcohol or other central nervous system depressants may cause additional reduction in alertness and impairment of ability to perform tasks.

Special precautions for use.

Seasonique should be used 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 with this medication.

The drug should be prescribed cautiously to patients who have certain factors predisposing to urinary retention (e.g., spinal cord injuries, benign prostatic hyperplasia), as levocetirizine may increase the risk of urinary retention.

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

Antihistamines suppress the response to skin allergy tests; therefore, the drug 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, the symptom may be intense and may require re-initiation of treatment. The symptom should resolve after resuming treatment.

If intolerance to certain sugars has been diagnosed, consult a physician before taking this medicinal product.

Use during pregnancy or breastfeeding.

Levocetirizine is contraindicated during pregnancy.

Levocetirizine passes into breast milk; therefore, if use of the drug is necessary, breastfeeding should be discontinued.

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.

During treatment with this medication, patients should refrain from driving or operating potentially hazardous machinery.

Method of administration and dosage.

The drug should be taken orally, regardless of food intake. The tablet should be swallowed whole with a small amount of water. It is recommended to take the daily dose as a single dose.

The drug is indicated for adults and children aged 6 years and older.

Recommended doses

Adults and children aged 12 years and older: the daily dose is 5 mg (1 film-coated tablet) once daily.

Elderly patients

Elderly patients with normal renal function do not require dose adjustment.

Dose adjustment is recommended for elderly patients with moderate to severe renal impairment.

Patients with renal impairment

For patients with impaired renal function, the dose should be adjusted according to the degree of renal impairment (creatinine clearance); see the table below.

Creatinine clearance (CC) is determined based on serum creatinine concentration (mg/dL) using the following formula:

Dosage of the drug for patients with impaired renal function

For children with renal impairment, the dose of the drug should be individually adjusted based on the patient's renal clearance and body weight.

There are no specific data regarding use in children with impaired renal function.

Patients with hepatic impairment

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

Paediatric population

Children aged 6 to 12 years: the recommended daily dose is 5 mg (1 film-coated tablet).

For children aged 2 to 6 years, dose adjustment is not feasible with this pharmaceutical form (film-coated tablet). It is recommended to administer levocetirizine in another pharmaceutical form suitable for paediatric use.

Duration of treatment

Patients with intermittent allergic rhinitis (disease symptoms lasting less than 4 days per week or less than 4 weeks per year) should be treated according to the disease and medical history; treatment may be discontinued if symptoms resolve and restarted upon recurrence of symptoms. For persistent allergic rhinitis (disease symptoms lasting more than 4 days per week and more than 4 weeks per year), continuous therapy may be considered during allergen exposure periods. There is clinical experience with levocetirizine use for at least a 6-month treatment period. In chronic conditions (chronic allergic rhinitis, chronic urticaria), the treatment duration may extend up to 1 year (data from clinical studies on the racemate).

Children.

The tablet form of the drug is not recommended for children under 6 years of age, as this pharmaceutical form does not allow appropriate dose adjustment. For this patient group, levocetirizine in another pharmaceutical form suitable for paediatric use is recommended.

Overdose.

Symptoms. Overdose symptoms may include somnolence in adults and initial excitation and increased irritability followed by somnolence in children.

Treatment. There is no specific antidote for levocetirizine. In case of overdose symptoms, symptomatic and supportive therapy is recommended. Gastric lavage may be considered shortly after drug intake. Haemodialysis is not effective for elimination of levocetirizine from the body.

Adverse reactions.

Immune system disorders: hypersensitivity, including anaphylaxis.

Metabolism and nutrition 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 system disorders: dyspnea.

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

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

Musculoskeletal and connective tissue disorders: myalgia, arthralgia.

General disorders: edema.

Investigations: weight gain, abnormal liver function tests.

Description of selected adverse reactions

Pruritus has been reported after discontinuation of levocetirizine.

Reporting suspected adverse reactions

Reporting suspected adverse reactions after authorization is very important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reactions via the national reporting system.

Shelf life. 4 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach and sight of children.

Packaging.

10 tablets in a blister; 1, 2, 3, or 10 blisters per cardboard box.

Pharmaceutical category.

Over-the-counter (without prescription).

Marketing Authorization Holder: LLC "BAUM PHARM GMBH Representation".

Address of the Marketing Authorization Holder:
66 Shyrokа Street, Lviv, 79052, Ukraine.

Manufacturer:

LLC "ASTRAFARM", Ukraine.

Manufacturer's address and site of manufacturing activity:

6 Kyivska Street, Vyshneve, Buchanskyi District, Kyiv Oblast, 08132, Ukraine.