Allerway (Tablets) Instructions for Use

Marketing Authorization Holder

Dr. Reddy’s Laboratories Ltd. (India)

Contact Information

Dr. Reddy’s Laboratories Ltd. (India)

ATC Code

R06AE09 (Levocetirizine)

Active Substance

Levocetirizine (Rec.INN registered by WHO)

Dosage Form

Allerway

Film-coated tablets, 5 mg: 7, 10, 14, 20, 21, or 30 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white or almost white, oval, biconvex, smooth on one side, with an engraving “R 5” on the other side; the core on cross-section is white to almost white.

Excipients: lactose monohydrate – 88 mg, microcrystalline cellulose, colloidal silicon dioxide, magnesium stearate.

Composition of the film coating Opadry white OY-58900: hypromellose (5 cP), titanium dioxide (E171), macrogol 4000.

7 pcs. – blisters (1) – cardboard packs.
7 pcs. – blisters (2) – cardboard packs.
7 pcs. – blisters (3) – cardboard packs.
10 pcs. – blisters (1) – cardboard packs.
10 pcs. – blisters (2) – cardboard packs.
10 pcs. – blisters (3) – cardboard packs.

Clinical-Pharmacological Group

Histamine H₁-receptor blocker. Antiallergic drug

Pharmacotherapeutic Group

Systemic antihistamines, piperazine derivatives

Pharmacological Action

Levocetirizine is the (R)-enantiomer of cetirizine, a potent and selective histamine antagonist, a histamine H₁-receptor blocker.

Levocetirizine affects the histamine-dependent stage of allergic reactions, and also reduces eosinophil migration, reduces vascular permeability, and limits the release of inflammatory mediators.

Levocetirizine prevents the development and alleviates the course of allergic reactions, has anti-exudative, antipruritic effects, and has practically no anticholinergic or antiserotonin action. In therapeutic doses, it has practically no sedative effect.

Pharmacokinetics

Absorption

After oral administration, Levocetirizine is rapidly and completely absorbed from the gastrointestinal tract. Bioavailability reaches 100%. Food intake does not affect the completeness of absorption, although it reduces its rate.

C_max in plasma is reached after 0.9 h and is 270 ng/ml. C_ss is reached after 2 days.

Distribution

Levocetirizine is 90% bound to plasma proteins. V_d is 0.4 l/kg.

Metabolism

It is metabolized in small amounts (less than 14%) in the body by N- and O-dealkylation (unlike other histamine H₁-receptor antagonists, which are metabolized in the liver by the cytochrome system) to form a pharmacologically inactive metabolite. Due to insignificant metabolism and lack of metabolic potential, interaction of levocetirizine with other drugs seems unlikely.

Elimination

T_1/2 in adults is 7.9±1.9 h. In young children, the half-life is shorter. In adults, the total clearance is 0.63 ml/min/kg. About 85.4% of the administered dose of levocetirizine is excreted by the kidneys unchanged by glomerular filtration and tubular secretion; about 12.9% – through the intestine.

Linearity (non-linearity)

The pharmacokinetic parameters of levocetirizine change linearly.

Special patient groups

Patients with renal impairment

In patients with renal impairment (creatinine clearance less than 40 ml/min), the clearance of levocetirizine is reduced. In patients on hemodialysis, total clearance is reduced by 80%. Less than 10% of levocetirizine is removed during a standard 4-hour hemodialysis procedure.

Patients with hepatic impairment

The pharmacokinetics of levocetirizine in patients with hepatic impairment have not been studied. In patients with chronic liver diseases (hepatocellular, cholestatic and biliary cirrhosis) who received a single dose of the racemic compound cetirizine at a dose of 10 or 20 mg, an increase in T_1/2 by 50% and a decrease in levocetirizine clearance by 40% were observed compared with healthy individuals.

Elderly patients

Data on pharmacokinetics in elderly patients are limited. With repeated administration of 30 mg of levocetirizine once a day for 6 days in 9 elderly patients (age from 65 to 74 years), the total clearance was approximately 33% lower than in younger adults. It has been shown that the distribution of the cetirizine racemate depends more on renal function than on age. This statement may also be applicable to levocetirizine, since both drugs, Levocetirizine and cetirizine, are excreted primarily in the urine. Therefore, in elderly patients, the dose of levocetirizine should be adjusted depending on renal function.

Children

Data from a pharmacokinetic study of levocetirizine in 14 children aged 6 to 11 years with a body weight of 20 to 40 kg after a single oral dose of 5 mg of levocetirizine showed that C_max and AUC values were approximately 2 times higher than the corresponding values in healthy adults in a cross-over controlled study. The mean C_max was 450 ng/ml, C_max was reached on average after 1.2 h, total clearance adjusted for body weight was 30% higher, and T_1/2 was 24% shorter in children than the corresponding values in adults. Special pharmacokinetic studies in children under 6 years of age have not been conducted. A retrospective pharmacokinetic analysis was conducted in 323 patients (181 children aged 1 to 5 years, 18 children aged 6 to 11 years, and 124 adults aged 18 to 55 years) who received one or more doses of levocetirizine from 1.25 mg to 30 mg. The data obtained during the analysis showed that taking levocetirizine at a dose of 1.25 mg in children aged 6 months to 5 years leads to plasma concentrations corresponding to those in adults taking 5 mg of levocetirizine once a day.

Indications

For adults and children aged 6 years and older for the treatment of

• Symptoms of allergic rhinitis, including perennial (persistent) and seasonal (intermittent) allergic rhinitis, and allergic conjunctivitis, such as itching, sneezing, nasal congestion, rhinorrhea, lacrimation, hyperemia of the conjunctiva;
• Hay fever;
• Urticaria;
• Other allergic dermatoses accompanied by itching and rash.

ICD codes

Dosage Regimen

Adults and children over 6 years

Orally, swallowed whole, with or without food, with a small amount of water.

The daily dose is 5 mg (1 tablet) once a day.

Duration of treatment

In the treatment of seasonal (intermittent) rhinitis (symptoms present for less than 4 days per week or total duration of symptoms less than 4 weeks) the duration of treatment depends on the duration of symptoms; treatment can be stopped when symptoms disappear and resumed when symptoms appear.

In the treatment of perennial (persistent) allergic rhinitis (symptoms present for more than 4 days per week and total duration of symptoms more than 4 weeks) treatment may continue throughout the period of allergen exposure.

There is clinical experience of continuous use of levocetirizine in adult patients for up to 6 months.

Missed dose

If a dose is missed, patients should not take a double dose to make up for the missed dose. The next dose should be taken at the usual time.

Patients with impaired renal function

The main route of elimination of levocetirizine from the body is renal excretion, therefore, when using the drug in elderly patients and patients with renal failure, the dose should be adjusted depending on the degree of renal failure, based on the assessment of creatinine clearance (ml/min).

Patients with mild renal impairment (creatinine clearance from 50 to 79 ml/min) do not require dose adjustment.

In patients with moderate renal impairment (creatinine clearance from 30 to 49 ml/min) the recommended dose is 5 mg every other day.

In patients with severe renal impairment (creatinine clearance less than 30 ml/min) the recommended dose is 5 mg once every 3 days.

Patients with renal and hepatic impairment

Dosing is carried out according to the above scheme.

Patients with impaired hepatic function only

No adjustment of the dosing regimen is required.

Children

The drug is contraindicated in children under 6 years of age.

The dosage regimen for children from 6 years of age corresponds to the dosage regimen for adults.

Adverse Reactions

Safety data obtained from the study of cetirizine

Uncommon (≥1/10000, <1000)

Mild and temporary adverse events such as fatigue, impaired concentration, drowsiness, headache, dizziness, agitation, dry mouth and gastrointestinal disorders (constipation) occurred. In some cases, hypersensitivity reactions and angioedema were observed.

Isolated cases of convulsions, photosensitivity reaction, liver damage, anaphylactic shock, circulatory disorders, deafness, malaise, itching, vasculitis, visual disturbances and nightmares have also been reported.

Clinical trial data

Clinical studies have shown that adverse reactions were observed in 14.7% of patients taking Levocetirizine at a dose of 5 mg compared with 11.3% in the placebo group. 95% of these adverse reactions were mild or moderate. In clinical studies, the rate of therapy discontinuation due to adverse reactions was 0.7% (4/538) in patients randomized to receive levocetirizine 5 mg and 0.8% (3/382) in patients randomized to the placebo group.

The following adverse reactions were identified in patients (n = 538) who participated in a clinical trial and used Levocetirizine at recommended doses (5 mg once daily).

With a frequency of 1-10%

Although the incidence of drowsiness in the levocetirizine group was higher than in the placebo group, in most cases this adverse event was mild or moderate.

Uncommon (0.1-1%)

Abdominal pain.

Post-marketing studies

During the post-marketing use of the drug, the following adverse reactions were observed.

Immune system disorders hypersensitivity reactions, including anaphylaxis.

Metabolism and nutrition disorders increased appetite.

Psychiatric disorders anxiety, aggression, agitation, hallucinations, depression, insomnia, suicidal ideation, nightmares.

Nervous system disorders: convulsions, sinus thrombosis of the dura mater, paresthesia, dizziness, vertigo, syncope, tremor, dysgeusia.

Eye disorders inflammatory manifestations, visual impairment, blurred vision, involuntary eye movements (nystagmus).

Cardiac disorders angina pectoris, tachycardia, palpitations.

Vascular disorders jugular vein thrombosis.

Respiratory, thoracic and mediastinal disorders worsening of rhinitis symptoms, dyspnea.

Gastrointestinal disorders nausea, vomiting.

Hepatobiliary disorders: hepatitis.

Skin and subcutaneous tissue disorders angioedema, exanthema, hypotrichosis, pruritus, rash, fissures, urticaria, photosensitivity/toxicity, persistent drug-induced erythema.

Musculoskeletal and connective tissue disorders myalgia, arthralgia.

Renal and urinary disorders dysuria, urinary retention.

General disorders and administration site conditions drug ineffectiveness and its interaction, dryness of mucous membranes, edema.

Investigations weight increased, abnormal liver function tests, cross-reactivity.

Description of selected adverse reactions

A small number of patients experienced pruritus after discontinuation of levocetirizine.

Reporting of suspected adverse reactions

It is important to report suspected adverse reactions after drug registration to ensure continuous monitoring of the benefit-risk ratio of the drug. Healthcare professionals are encouraged to report any suspected adverse drug reactions through the national adverse reaction reporting systems of the member states of the Eurasian Economic Union.

Contraindications

• Hypersensitivity to levocetirizine, cetirizine, hydroxyzine, any piperazine derivative or to any of the excipients included in the drug;
• End-stage renal failure (creatinine clearance less than 10 ml/min).

Use in Pregnancy and Lactation

Pregnancy

Data on the use of levocetirizine during pregnancy are virtually absent or limited (less than 300 pregnancy outcomes). However, the use of cetirizine, the racemate of levocetirizine, during pregnancy (more than 1000 pregnancy outcomes) was not associated with malformations and intrauterine and neonatal toxic effects. Animal studies have not revealed direct or indirect adverse effects on pregnancy, embryonic and fetal development, childbirth and postnatal development.

The use of levocetirizine during pregnancy may be considered if necessary.

Breastfeeding

Cetirizine, the racemate of levocetirizine, is excreted in breast milk. Therefore, excretion of levocetirizine in breast milk is also likely. Breastfed infants may experience adverse reactions to Levocetirizine. Therefore, caution should be exercised when prescribing levocetirizine during breastfeeding.

Fertility

Clinical data on levocetirizine are not available.

Use in Hepatic Impairment

No dose adjustment is required.

Use in Renal Impairment

Contraindicated in end-stage renal failure (creatinine clearance less than 10 ml/min).

In patients with severe renal impairment (creatinine clearance less than 30 ml/min), the recommended dose is 5 mg once every 3 days.

Pediatric Use

The drug is contraindicated in children under 6 years of age.

The dosage regimen for children from 6 years of age corresponds to the dosage regimen for adults.

Geriatric Use

In elderly patients, the dose of levocetirizine should be adjusted depending on renal function.

Special Precautions

The intervals between doses should be selected individually, depending on renal function.

Caution is recommended when consuming alcohol concomitantly.

Caution should be exercised in patients with predisposing factors for urinary retention (e.g., spinal cord injury, prostatic hyperplasia), as Levocetirizine may increase the risk of urinary retention.

Caution should be exercised in patients with epilepsy and increased seizure readiness, as Levocetirizine may cause exacerbation of seizures.

The response to skin allergy tests is suppressed by antihistamines, and it is necessary to refrain from taking the drug for 3 days before testing.

Pruritus may occur after discontinuation of levocetirizine, even if such symptoms were not present at the beginning of treatment. Symptoms may resolve on their own. In some cases, symptoms may be severe and may require resumption of treatment. After resuming treatment, these symptoms should resolve.

Excipients

Allerway contains lactose. Patients with rare hereditary galactose intolerance, lactase deficiency or glucose-galactose malabsorption should not take this drug.

Effect on ability to drive vehicles and operate machinery

Levocetirizine may lead to increased drowsiness, therefore, the drug may affect the ability to drive vehicles or operate machinery. During the treatment period, it is necessary to refrain from engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Symptoms drowsiness (in adults), initially agitation and restlessness may appear, followed by drowsiness (in children).

Treatment it is necessary to perform gastric lavage or take activated charcoal if little time has passed after taking the drug. Symptomatic and supportive therapy is recommended. There is no specific antidote. Hemodialysis is not effective.

Drug Interactions

Studies of the interaction of levocetirizine with other drugs have not been conducted. In the study of drug interactions of the cetirizine racemate with antipyrine, azithromycin, cimetidine, diazepam, erythromycin, glipizide, ketoconazole and pseudoephedrine, no clinically significant undesirable interactions were identified.

With simultaneous use with theophylline (400 mg/day), the total clearance of cetirizine decreases by 16% (the kinetics of theophylline does not change).

In a study with the simultaneous administration of ritonavir (600 mg twice daily) and cetirizine (10 mg/day), it was shown that the exposure to cetirizine increased by 40%, while the exposure to ritonavir changed insignificantly (-11%).

In sensitive patients, the simultaneous intake of levocetirizine and alcohol or medicinal products that have a depressant effect on the CNS may cause drowsiness and a deterioration in performance.

Storage Conditions

The drug should be stored at a temperature not exceeding 25°C (77°F).

Shelf Life

The shelf life is 3 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.