Ergocetal

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

Composition:

Active substance: levocetirizine dihydrochloride;

1 tablet contains levocetirizine dihydrochloride 5 mg;

Excipients: microcrystalline cellulose; lactose monohydrate; colloidal silicon dioxide anhydrous; magnesium stearate;

Coating: film coating mixture Opadray II White: hypromellose (hydroxypropylmethylcellulose); lactose monohydrate; titanium dioxide (E 171); polyethylene glycol (macrogol).

Medicinal form. Film-coated tablets.

Main physicochemical properties: oval, biconvex film-coated tablets of white or almost white color.

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 class of competitive histamine antagonists. Its pharmacological effect is mediated through 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 suppresses the progression of allergic reactions, exerting anti-exudative, anti-pruritic, and anti-inflammatory effects, with minimal anticholinergic and anti-serotonergic activity.

Pharmacokinetics.

The pharmacokinetic parameters of levocetirizine exhibit linear kinetics and are independent of dose and time, showing low inter-individual variability. The pharmacokinetic profile after administration of the single enantiomer is identical to 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 dose and is not altered by food intake; however, the maximum plasma concentration (Cmax) is reduced and reached later. Bioavailability is 100%.

It is known that the effect of the drug begins within 12 minutes after a single dose in 50% of patients, and in 95% of patients within 0.5–1 hour. In adults, Cmax is reached within 50 minutes after a single oral therapeutic dose. Steady-state plasma concentration is achieved after 2 days of daily dosing. Cmax is 270 ng/mL after a single dose and 308 ng/mL after repeated administration of 5 mg once daily.

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. Animal studies have shown the highest concentrations in the liver and kidneys, and the lowest in central nervous system tissues. The distribution of levocetirizine is limited, with a volume of distribution of 0.4 L/kg. Plasma protein binding in humans is 90%.

Metabolism. In humans, the extent of metabolism is less than 14% of the administered dose; therefore, differences due to genetic polymorphism or concomitant use of enzyme inhibitors are expected to be minimal. Metabolic processes include aromatic oxidation, N- and O-dealkylation, and conjugation with taurine. Dealkylation is primarily mediated by cytochrome CYP3A4, whereas aromatic oxidation involves multiple and/or undefined CYP isoforms. Levocetirizine does not affect the activity of cytochrome isoforms 1A2, 2C9, 2C19, 2D6, 2E1, and 3A4 at concentrations significantly exceeding those achieved after a 5 mg oral dose. Due to its low extent of metabolism and lack of inhibitory potential, drug interactions with levocetirizine (or by levocetirizine) are unlikely.

Elimination. The drug is eliminated via two pathways: glomerular filtration and active tubular secretion. The plasma elimination half-life (T1/2) in adults is 7.9 + 1.9 hours. The T1/2 of the drug is shorter in younger 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 dose is excreted in feces.

Special populations

Renal impairment

The apparent clearance of levocetirizine correlates with creatinine clearance. Therefore, dosing intervals of levocetirizine should be adjusted in patients with moderate to severe renal impairment based on creatinine clearance. In patients with anuria and end-stage renal disease, total clearance is reduced by approximately 80% compared to individuals without renal impairment. 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, cetirizine, hydroxyzine, to any other piperazine derivatives, or to any excipients of the medicinal product.

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.

Studies on levocetirizine interactions (including with CYP3A4 inducers) have not been conducted. Studies on cetirizine (the racemate compound) interactions showed that concomitant administration with antipyrine, azithromycin, cimetidine, diazepam, erythromycin, glipizide, ketoconazole, or pseudoephedrine does not result in clinically significant adverse effects. When administered concomitantly with theophylline (400 mg per day), a slight decrease (by 16%) in cetirizine clearance was observed (theophylline distribution remained unchanged). In a study of multiple-dose administration of ritonavir (600 mg twice daily) and cetirizine (10 mg daily), cetirizine exposure increased by approximately 40%, while ritonavir distribution was slightly altered (–11%) with concomitant cetirizine 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 co-ingestion of food reduces the rate of absorption.

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

Special precautions for use.

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

When prescribing the drug to patients with factors provoking urinary retention (e.g., spinal cord injuries, benign prostatic hyperplasia), it should be considered that 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 exacerbation of seizures.

Antihistamines suppress the response to skin allergy tests; therefore, administration of the drug should be discontinued 3 days prior to testing (elimination period).

Pruritus may occur after discontinuation of levocetirizine, even if this symptom was not observed prior to starting treatment. This symptom may resolve spontaneously. In some cases, the symptom may be intense and re-initiation of treatment may be required. The symptom should resolve upon resuming treatment.

The tablet form of the drug is not recommended for children under 6 years of age, as this dosage form does not allow for appropriate dose adjustment. This patient group should be prescribed levocetirizine in a pharmaceutical form suitable for pediatric use.

Use during pregnancy or breastfeeding.

Levocetirizine is contraindicated during pregnancy.

Cetirizine passes into breast milk; therefore, if treatment with this 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 influence reaction rate when driving or operating machinery.

Patients should refrain from driving or operating potentially hazardous machinery during treatment with this drug.

Method of Administration and Dosage

The medicinal product should be administered to 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 tablet) once daily.

Paediatric population

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

For children under 6 years of age, dose adjustment is not feasible with this medicinal form (film-coated tablet). Levocetirizine in another pharmaceutical form suitable for paediatric use is recommended.

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 (see section "Renal impairment").

Renal impairment

In patients with impaired renal function, dosage must be adjusted according to the degree of renal impairment (creatinine clearance) as specified in the table below.

To do this, determine the patient's creatinine clearance (CrCl) in mL/min from serum creatinine concentration (mg/dL) using the following formula:

Dosage adjustment of the drug for patients with renal function impairment

In children with impaired renal function, the dose of the medicinal product should be individually adjusted according to the patient's renal clearance and body weight.

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

Hepatic impairment

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

Administration

Take the tablet orally, independent of food intake. The tablet should be swallowed whole with a small amount of water. It is recommended to administer the daily dose as a single intake.

Duration of treatment

Patients with intermittent allergic rhinitis (duration of symptoms less than 4 days per week or less than 4 weeks per year) should be treated according to the course of the disease and medical history; treatment may be discontinued if symptoms resolve and may be restarted upon recurrence of symptoms. In case of persistent allergic rhinitis (duration of symptoms more than 4 days per week or more than 4 weeks per year) during allergen exposure, continuous therapy may be recommended. Clinical experience with levocetirizine use for at least 6 months of treatment is available. In chronic conditions (chronic allergic rhinitis, chronic urticaria), the duration of treatment may last up to 1 year (data available from clinical studies using the racemate).

Children.

The tablet form of the medicinal product should not be used in children under 6 years of age, as this dosage form does not allow for the necessary dose adjustment. This patient group should be prescribed levocetirizine in a dosage form suitable for pediatric use.

Overdose.

Symptoms. Symptoms of overdose in adults may include somnolence. In children, initial symptoms may include excitation and increased irritability followed by somnolence.

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.

Hemodialysis is not effective for elimination of 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, paresthesia, dizziness, fainting, tremor, dysgeusia.

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

Cardiac disorders: palpitations, tachycardia.

Eye disorders: visual disturbance, blurred vision, nystagmus.

Ear and labyrinth disorders: vertigo.

Hepatobiliary disorders: hepatitis.

Renal and urinary disorders: dysuria, urinary retention.

Respiratory, thoracic and mediastinal disorders: dyspnea.

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

Skin and subcutaneous tissue disorders: angioedema, persistent 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

There have been reports of pruritus following discontinuation of levocetirizine.

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life. 2 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 blister per carton.

10 tablets in a blister; 3 blisters per carton.

Supply category. Over-the-counter.

Manufacturer. JSC "KYIV VITAMIN PLANT".

Manufacturer's address and location of operations.

38 Kopilivska Street, Kyiv, 04073, Ukraine.

Web-site: www.vitamin.com.ua