Allerset

INSTRUCTION for medical use of the medicinal product Allercet (Allercet)

Composition:

Active substance: levocetirizine dihydrochloride;

One film-coated tablet contains levocetirizine dihydrochloride 5 mg;

Excipients: lactose monohydrate (Pharmatose 200M), microcrystalline cellulose (Avicel PH 102), lactose monohydrate (Super Tab 11SD), colloidal anhydrous silicon dioxide, magnesium stearate;

Film coating composition: Opadry Y-1-7000 White (hypromellose, titanium dioxide (E 171), macrogol).

Pharmaceutical form. Film-coated tablets.

Main physicochemical characteristics: oval, biconvex, film-coated tablets, white in color, with engraving «I» and «12» on one side and a break line on the other side.

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 for H1-histamine receptors is twice as high for levocetirizine as for cetirizine. Levocetirizine affects the histamine-dependent phase of allergic reaction development, 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-serotonin activity.

Pharmacokinetics.

Pharmacokinetic parameters of levocetirizine show linear dependence and are independent of dose and time, with low variability among different patients. The pharmacokinetic profile after administration of a single enantiomer is the same as that observed with cetirizine. No chiral inversion is observed during absorption or elimination.

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

The onset of drug action occurs within 12 minutes after a single dose in 50% of patients and within 0.5–1 hour in 95% of patients. In adults, Cmax in blood plasma is achieved within 50 minutes after a single oral therapeutic dose. Steady-state plasma concentration is reached after 2 days of drug administration. Cmax is 270 ng/mL after a single dose and 308 ng/mL after repeated administration of a 5 mg dose once daily.

Distribution. There is no available information on the distribution of the drug in human tissues or on the penetration of levocetirizine across the blood-brain barrier. In animal studies, the highest concentrations were observed in the liver and kidneys, while the lowest concentrations were found in central nervous system (CNS) 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, less than 14% of the levocetirizine dose undergoes metabolism. 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 is primarily mediated by cytochrome CYP3A4, whereas 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 oral administration of a 5 mg dose. Due to the low extent of metabolism and lack of inhibitory effect on metabolic enzymes, drug interactions (both levocetirizine affecting other drugs and vice versa) are unlikely.

Excretion. Drug elimination occurs via two pathways: glomerular filtration and active tubular secretion. The elimination half-life (T1/2) of the drug from plasma in adults is 7.9 ± 1.9 hours. The T1/2 in younger children is shorter. The mean apparent total 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.

Special populations

Renal impairment

The apparent clearance of levocetirizine correlates with creatinine clearance. Therefore, dosing intervals for levocetirizine in patients with moderate to severe renal impairment 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 without such 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, or 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 disorders of galactose intolerance, lactase deficiency, or glucose-galactose malabsorption.

Interaction with other medicinal products and other forms of interaction.

Studies on interactions of levocetirizine (including with CYP3A4 inducers) have not been conducted. Interaction studies with cetirizine (the racemate compound) showed that no clinically significant adverse effects were observed when administered concomitantly with antipyrine, azithromycin, cimetidine, diazepam, erythromycin, glipizide, ketoconazole, or pseudoephedrine. In a multiple-dose study, concomitant administration with theophylline (400 mg per day) resulted in a slight reduction (by 16%) in cetirizine clearance (theophylline distribution remained unchanged). In another multiple-dose study, coadministration of ritonavir (600 mg twice daily) and cetirizine (10 mg per day) increased cetirizine exposure by approximately 40%, while ritonavir distribution was slightly altered (−11%) when cetirizine was coadministered.

There are no data regarding potentiation of sedative effects when sedatives are 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 absorption of the drug, but simultaneous food intake reduces the rate of its absorption.

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

Special precautions for use

The drug should be used with caution in patients with chronic renal insufficiency (dose adjustment is 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 taken into account that levocetirizine may increase the risk of urinary retention.

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

Antihistamines suppress the response to skin allergy tests; therefore, 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 present before treatment initiation. The symptom may resolve spontaneously. In some cases, the symptom may be intense and re-treatment may be required. The symptom should resolve after re-initiation of treatment.

The tablet form of the drug 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 should be prescribed levocetirizine in a dosage form suitable for pediatric use.

Patients with known sensitivities to certain sugars should consult a physician before taking this medicinal product.

Use during pregnancy or breastfeeding

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

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 other potentially hazardous machinery during treatment with this drug.

Dosage and Administration

The medicine is intended 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 (see section "Renal Impairment").

Renal Impairment

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

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

Dosage adjustment of the drug for patients with renal function impairment

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

There are no specific data available regarding use in children with renal impairment.

Hepatic impairment

Dose adjustment is not required in patients with hepatic impairment. In patients with both hepatic and renal impairment, the dosage regimen should be adjusted 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 medicinal form. It is recommended to prescribe levocetirizine in a pharmaceutical form suitable for paediatric use.

Method of administration

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

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 course of the disease and medical history: treatment may be discontinued if symptoms resolve and may be restarted upon recurrence of symptoms. In cases of persistent allergic rhinitis (disease symptoms lasting more than 4 days per week or more than 4 weeks per year), continuous therapy may be considered during allergen exposure periods. Clinical experience supports the use of levocetirizine for at least a 6-month treatment period. For chronic conditions (chronic allergic rhinitis, chronic urticaria), treatment duration may extend up to 1 year (data available from clinical studies using the racemate).

Children

The tablet form of the medicinal product should not be administered to children under 6 years of age, as this pharmaceutical form does not allow for appropriate dose adjustment. For this patient group, levocetirizine in a pharmaceutical form suitable for paediatric use is recommended.

Overdose

Symptoms: Symptoms of overdose in adults may include drowsiness. In children, initial symptoms may include 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 may be considered shortly after drug intake. Hemodialysis is ineffective for removing 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, uncontrolled circular eye movements.

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, persistent drug eruptions, pruritus, rash, urticaria.

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

General disorders: Oedema.

Investigations: Weight gain, abnormal liver function tests.

Description of selected adverse reactions

Pruritus has been reported after discontinuation of levocetirizine.

Shelf life. 3 years.

Storage conditions.

Store at a temperature not exceeding 30 °C. Keep out of reach of children.

Packaging.

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

Supply category. Over-the-counter.

Manufacturer.

MICRO LABS LIMITED.

Manufacturer's address and site of operations.

Plot No. S.155 to S.159 & N1, Verna Industrial Estate, Phase III & Phase IV, Verna Salcette, IN-403 722, India.