Antihistaminic drugs for system use. ATC Code R06A Е09.
Levocetirizine – is an active stable R-enantiomer of cetirizine, which belongs to the competitive antagonists group of histamine H1-receptors. The levocetirizine affinity to histamine H1- receptors is 2 times higher than that of cetirizine. Effects on the histamine-dependent stage of the allergic reaction development, reduces migration of eosinophils, vascular permeability, limits the release of inflammatory mediators. Prevents the development and facilitates the course of allergic reactions, has antiexudative, antipruritic, anti-inflammatory effect, almost has no anticholinergic and antyserotonin actions. Almost has no sedative effect at therapeutic doses.
Pharmacokinetics of levocetirizine varies linearly and is almost indistinguishable from those of cetirizine.
Absorption. Levocetirizine is rapidly absorbed after oral administration. Food intake does not effect on the extent of absorption, but decreases its speed. Bioavailability is 100 %. In 50 % of patients the drug action developes within 12 minutes after single dose administration, and in 95 % - is in 0.5-1 hours.
The maximum concentration (Cmax) is achieved in 50 minutes after a single dose administration and maintained for 2 days.
Distribution. There is no information on drug distribution in human tissues, as well as on levocetirizine penetration through the blood-brain barrier. In the animal studies, the highest concentration is in liver and kidneys, and the lowest - in central nervous system tissues. The volume of distribution was 0.4 L/kg. Binding to plasma proteins is 90 %.
Biotransformation. About 14 % of levocetirizine is metabolized in human body. The process of metabolism includes the oxidation, N-and O-dealkylation and adhesion with taurine. Dealkylation primarily occurs with cytochrome CYP 3A4, while a number of cytochrome isoforms is involved in the oxidation process. Levocetirizine has no effect on the activity of cytochrome isoenzymes 1A2, 2C9, 2C19, 2D6, 2E1, 3A4 at concentrations, which exceed even maximum after dose of 5 mg orally administration. As metabolism degree is low and there is no enhancement of inhibitory action, interaction of levocetirizine with other substances (and vice versa) is unlikely.
Excretion. Drug excretion is mainly conducted due to glomerular filtration and active tubular secretion. The half-life (T1/2) in adults is 7.9+1.9 hours, total clearance - 0.63 ml/min/kg. 85.4 % of dose is excreted unchanged with urine, about 12.9 % - with feces.
In patients with renal impairment (creatinine clearance 1/2 prolongs (for example, in patients who are on hemodialysis, total clearance is reduced by 80 %), what is required the selection of appropriate dosing regimen. In a standard 4-hour hemodialysis, small portion (less than 10 %) of levocetirizine is removed.
Indications for use.
Symptomatic treatment of allergic rhinitis, including perennial allergic rhinitis; chronic idiopathic urticaria.
Hypersensitivity to levocetirizine, to other piperazine derivatives or to any other drug component.
Severe chronic renal insufficiency (clearance of creatinine is less than 10 ml/min).
Appropriate precautions for use.
Do not exceed the recommended dose.
Use with caution in patients with chronic renal failure (correction of dosing regimen is required); in elderly patients with chronic renal failure (reduction in glomerular filtration rate is possible). It is necessary to refrain from drinking alcohol during drug administration. Food intake does not effect on the extent of drug absorption, but reduces its absorption rate.
If there are certain factors in patients that provoke urine retention (eg, spinal cord injury, prostatic hyperplasia) it is necessary to pay attention to drug prescription, since levocetirizine may increase the risk of urinary retention.
Administration during pregnancy and lactation.
Administration of levocetirizine during pregnancy is contraindicated. Cetirizine sinks into breast milk, so if drug administration is necessary, breastfeeding should be discontinued.
Influence on ability to drive car or operating machinery.
It is necessary to refrain from driving car or operating other machines during the drug treatment.
Drug administration in tablet form is not recommended for children under 6 years, as this dosage form makes it impossible to carry out the necessary dosing regimen correction.
Posology and method of administration.
Prescribe the drug for adults and children from 6 years internally at a daily dose of 5 mg 1 time per day. Take a pill without regard to food. Tablet should be swallowed whole, with some water.
Dose adjustment for elderly patients with normal renal function is not required.
For patients with impaired renal function the dose calculation should be carried out, based on creatinine clearance in accordance with the table.
To use this dosing table, it is necessary to estimate patient’s creatinine clearance (CLCR) in ml/min. CLCR (ml/min) should be evaluated on the content of serum creatinine (mg/dL), using the following formula:
[140 – age (years)] x body weight (kg)
(x 0,85 for women)
72 x serum creatinine (mg/dL)
Dose adjustment in patients with impaired renal function:
Creatinine clearance, mL/min.
Dosage and dosing frequency
Normal renal function
5 mg 1 time per day
Slightly renal disorder
5 mg 1 time per day
Mildly renal disorder
5 mg 1 time per day
Severe renal disorder
5 mg 1 time per 3 days
Renal diseases end-stage
Patients on dialysis
For pediatric patients with impaired renal function the dose should be adjusted individually according to the patient's renal clearance and his body weight.
Patients with hepatic insufficiency don’t require the dosing regimen adjustment. For patients with hepatic and renal insufficiency the dose adjustment is according to the table above.
Duration of administration: patients with periodic allergic rhinitis (duration of the disease symptoms is 4 days per week and for more than 4 weeks) during the contact with allergens, permanent therapy may be proposed for patient. In chronic diseases (chronic allergic rhinitis, chronic urticaria), treatment duration is up to 1 year.
Symptoms: symptoms of overdose may include drowsiness in adults and the baseline excitement and increased irritability, followed by drowsiness in children.
Treatment. Specific antidote to levocetirizine doesn’t exist. If symptoms of overdose are appeared, then symptomatic and supportive therapy is recommended. The necessity for gastric lavage should be considered soon after the drug administration. Hemodialysis is not effective for levocetirizine excretion from the body.
Skin and subcutaneous tissue: angioedema, persistent drug rashes, pruritus, rash, urticaria.
Musculoskeletal system, connective tissue and bones: myalgia
Other: weight gain, liver function tests deviations from normal values.
General disorders and administration site condition: swelling.
Interaction with other medicinal products and other forms of interaction.
Concurrent usage of the preparation with antipyrine, pseudoephedrine, cimetidine, ketoconazole, erythromycin, azithromycin, glipizide or diazepam has not clinically significant adverse interactions. Concomitant usage with theophylline (400 mg/day) reduces the total clearance of levocetirizine by 16 %, and theophylline kinetics does not change. In the study of ritonavir repeated administration (600 mg 2 times daily) and cetirizine (10 mg daily) degree of cetirizine exposure had been increased by approximately 40 %, whereas the distribution of ritonavir had been changed (- 11 %) up to the parallel administration of cetirizine .
Concurrent usage of levocetirizine with drugs that inhibit the function of central nervous system (tranquilizers, tricyclic antidepressants, MAO inhibitors), and alcohol may cause drowsiness.
There is no data on the increasing sedatives effect during the use of levocetirizine at therapeutic doses. But it is necessary to avoid the use of sedatives during drug administration
Food intake does not effect on extent of drug absorption, but reduces its rate of absorption.
Store at a temperature below 25 oC.
Keep it out of reach of children.
10 tablets are in blister, 1 or 3 or 10 blisters are in a carton pack.
Conditions of supply:
Date of last revision. 23.01.2014 No 67
symptomatic treatment of seasonal allergic rhinitis including whole-year allergic ,
the chronic idiopathic urticaria.
1 film coated tablet contains Levocetirizine hydrochloride 5 mg.