ZELARY Film-coated tablet Ref.[115280] Active ingredients: Cetirizine

Absorption

Cetirizine is well absorbed from the gastro-intestinal tract and peak plasma concentrations of 300 ng/mL are reached within 1 hour after oral administration. The extent of absorption of cetirizine is not reduced with food, although the rate of absorption is decreased. The extent of bioavailability is similar when cetirizine is given as solutions or tablets.

No accumulation is observed for cetirizine following daily doses of 10 mg for 10 days. The distribution of pharmacokinetic parameters such as peak plasma concentration (C_max) and area under curve (AUC), is unimodal.

Distribution

The apparent volume of distribution is 0,50 L/kg. A high proportion of cetirizine is bound to human plasma proteins (93 ± 0,3 %). Cetirizine does not modify the protein binding of warfarin.

Biotransformation

Cetirizine does not undergo extensive first-pass metabolism.

Elimination

The terminal half–life in adults is approximately 10 hours, in children aged 6 to 12 years, 6 hours, in children aged 2 to 6 years, 5 hours.

Cetirizine is eliminated faster in children, and slower in patients with hepatic or renal impairment (creatinine clearance < 40 mL/min), with a resultant increase in half-life and decrease in clearance. The cumulative urinary excretion represents about two thirds of the dose given in both adults and children.

Linearity/non-linearity

Pharmacokinetics are linear over the range of 5 to 60 mg, with plasma concentrations increasing proportionately with increasing doses.

Pharmacokinetics in special patient groups

Elderly

Following a single 10 mg oral dose in elderly patients, half-life increases by about 50 % and clearance decreases by 40 % compared to younger patients. The decrease in cetirizine clearance in these elderly patients appears to be related to their decreased renal function.

Renally impaired patients

The pharmacokinetics of cetirizine are similar in patients with mild impairment (creatinine clearance higher than 40 mL/min) and patients with normal renal function. Patients with moderate renal impairment have a 3-fold increase in half-life and 70 % decrease in clearance compared to patients with normal renal function.

Patients on haemodialysis (creatinine clearance less than 7 mL/min) given a single oral 10 mg dose of cetirizine have a 3-fold increase in half-life and a 70 % decrease in clearance compared to patients with normal renal function. Cetirizine is poorly cleared by haemodialysis. Dosing adjustment is necessary in patients with moderate or severe renal impairment (see section 4.2).

Hepatically impaired patients

Patients with chronic liver diseases (hepatocellular, cholestatic and biliary cirrhosis) given 10 or 20 mg of cetirizine as a single dose have a 50 % increase in half-life along with a 40 % decrease in clearance compared to healthy patients.

Dosing adjustment is only necessary in hepatically impaired patients if concomitant renal impairment is present.

Paediatric population

Children, infants and toddlers:

The terminal half-life in children aged 6 to 12 years is 6 hours; in children aged 2 to 6 years, 5 hours.

This is consistent with the urinary excretion half-life of the medicine.

In infants and toddlers aged 6 to 24 months, it is reduced to 3,1 hours.