Clinico-pharmacological group: the histamine H1 receptor. Allergy medication
Pharmaco-therapeutic group: H1-histamine receptor blocker
Antiallergic agent. Levocetirizine, (R) enantiomer of cetirizine, is a selective antagonist of the peripheral histamine H1 receptors. Levocetirizine affinity (Ki = 3.2 nmol / L) histamine with H1-receptors is 2 times higher than that of cetirizine (Ki = 6.3 nmol / L). Pharmacokinetic studies in healthy volunteers have shown that when applied to the skin and mucous membrane of the nose activity of levocetirizine in half dose comparable activity in whole cetirizine dose.
Levocetirizine inhibits eotaxin-induced eosinophil transendothelial migration of cells in the skin and lungs. Pharmacodynamic studies have shown three main suppressive effect of levocetirizine 5 mg in the first 6 hours after exposure to pollen: emission suppression VCAM-1, a change in vascular permeability and a decrease in eosinophil activation. Like cetirizine effect against histamine-induced cutaneous reactions does not depend on the plasma concentrations of the drug.
Levocetirizine prevents the development and facilitates the allergic reactions, has antiekssudativnoe, antipruritic effect, practically no anticholinergic and antiserotoninovogo action.
Levocetirizine 5 mg promotes inhibition of inflammatory-exudative reaction to histamine to the same extent as cetirizine 10 mg. ECG revealed no significant effect of levocetirizine on the QT interval.
After oral administration, levocetirizine is rapidly absorbed from the gastrointestinal tract. Food intake does not affect the absorption of completeness, though its speed is reduced. Cmax plasma levels achieved after 0.9 h after a single ingestion. The equilibrium state is reached after 2 days. Cmax after single and repeated (5 mg daily) comprise receiving 270 ng / ml and 308 ng / ml, respectively.
Plasma protein binding is 90%. Data on the distribution of the drug in tissues and no penetration through the BBB. Vd is 0.4 L / kg. Provided with breast milk.
Less than 14% of the dose is metabolized in the liver by the oxidation of the aromatic ring, N- and O-dealkylation and conjugation with taurine. Catalyzed dealkylation preferably CYP3A4, and the oxidation of the aromatic rings are involved isoform CYP. Levocetirizine did not affect the activity of isozymes CYP1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 at concentrations much higher than peak concentrations after oral administration of 5 mg. Due to the slight metabolism and absence of metabolic suppression of the interaction of levocetirizine with other substances is unlikely.
T1 / 2 was 7.9 ± 1.9 h. Total clearance was 0.63 ml / min / kg. Levocetirizine and its metabolite derived mainly kidneys (85.4% of the dose), by glomerular filtration and active tubular secretion. Excretion through the gut is 12.9%.
The pharmacokinetics of levocetirizine is linear, not dose-dependent and time and has small differences in different subjects. The pharmacokinetic profiles of a single enantiomer of cetirizine and similar. When vacuuming or excretion occurs chiral inversion.
The total clearance of levocetirizine is correlated with CC (this should be considered when determining the intervals between doses in patients with moderate or severe renal impairment). When anuria total clearance is reduced by about 80% as compared with healthy subjects. In the standard procedure, a 4-hour dialysis output less than 10% of levocetirizine.
Symptomatic treatment of the symptoms of year-round and seasonal allergic rhinitis (including persistent allergic rhinitis) and allergic conjunctivitis: sneezing, rhinorrhea, lacrimation, conjunctival hyperemia, hay fever (hay fever), urticaria (including chronic idiopathic urticaria), and other allergic dermatitis, accompanied by itching and rash, angioedema.
Inside, regardless of meals.
Adults and children older than 6 years - 5 mg 1 time / day.
Children aged 2-6 years - 1.25 mg 2 times / day.
The duration of treatment depends on the type, duration and course of the symptoms. It requires 3-6 weeks and when short term exposure is usually sufficient pollen dosing for 1 week to treat hay fever.
CNS: often - headache, drowsiness, fatigue, rarely - fatigue.
From the digestive system: often - dry mouth, rarely - abdominal pain, rarely - nausea, violation of liver function tests.
Allergic reactions: seldom - angioedema, pruritus, rash, urticaria, anaphylaxis.
Other: very rarely - weight gain, dyspnea.
Severe renal insufficiency (creatinine clearance below 10 ml / min), children under 2 years of age, hypersensitivity to levocetirizine.
Pregnancy and breast-feeding
Clinical studies of levocetirizine in pregnancy. Not recommended for use during pregnancy and lactation (breastfeeding). special instructions
Elderly patients with moderate or severe renal impairment may require correction dosing regime.
Patients with impaired renal function requires correction mode depending on the spacecraft.
For patients with isolated liver dysfunction any dose change is required. In patients with combined liver and kidney recommended dose of refinement.
Patients should abstain from alcohol during use of levocetirizine.
Use in Pediatrics
Levocetirizine is used in children older than 2 years in a special dosage form.
Effects on ability to drive vehicles and management mechanisms
Comparative clinical studies have revealed no evidence of impaired level of consciousness, the reaction time or the ability to drive vehicles after receiving the recommended dose of levocetirizine. However, some patients may experience drowsiness, fatigue or asthenia during the reception. It should be used with caution in patients who drive vehicles and engaged in activities that require speed of psychomotor reactions.
Decreasing clearance cetirizine (16%) was observed during multiple introductions of theophylline (400 mg 1 time / day), the pharmacokinetics of theophylline when administered simultaneously cetirizine did not change.
In susceptible patients simultaneous use of levocetirizine or ethanol and other CNS depressing means can lead to potentiation of inhibitory effects on the CNS.