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ATC Code: R01B A52.
Pharmacology: Pharmacodynamics: The pharmacodynamic activity of cetirizine-pseudoephedrine is directly related to an additive effect of the activity of each of its components. Cetirizine is a H1-receptor antagonist with additional anti-allergic properties: it inhibits the histamine-related early phase of the allergic reaction and also reduces the migration of certain inflammatory cells and the release of certain mediators associated with the late allergic response; it reduces the histamine or pollen-induced reactions in nasal provocation tests.
Pseudoephedrine is an orally active sympathomimetic agent with predominantly alphamimetic properties. Due to its vasoconstrictive activity, it has a decongestive effect on the nasal mucosa.
Pharmacokinetics: After oral administration, cetirizine is rapidly and almost completely absorbed. Maximal plasma concentrations are generally obtained within 1 hour under fasting conditions. Cetirizine does not undergo any appreciable first pass metabolism. After repeated oral administration, the daily urinary excretion of unchanged cetirizine is approximately 65% of the dose. The absorption and the elimination of cetirizine are independent of the dose. The plasma half-life of cetirizine is approximately 9 hours. This value is increased in patients with reduced renal function. Cetirizine is highly bound to plasma protein (93%). Its volume of distribution is small: approximately 0.5 l/kg.
Pseudoephedrine given as the sustained-release formulation cetirizine-pseudoephedrine provides maximum plasma levels 2 to 6 hours after multiple dosing. It is excreted mainly unchanged in the urine. The rate of urinary excretion is reduced in case of alkalinisation of urine, especially at pH-values above 5.5. After repeated oral administration (every 12 hours), at steady-state, the apparent elimination half-life is estimated to be approximately 9 hours. A high fat meal was not found to modify the bioavailability of both active ingredients, but it resulted however in a reduced and delayed peak plasma concentration of cetirizine. There was no evidence for a relevant pharmacokinetic interaction between cetirizine and pseudoephedrine. The dose should be reduced to half the usual recommended dose in patients with renal insufficiency.
Toxicology: Pre-clinic data: Animals studies (performed with cetirizine and pseudoephedrine combined at the ratio 5:120 w/w) have demonstrated a no-toxic effect level ≥30 mg/kg/day in the rat and 40 mg/kg/day in the Cynomoglus monkey (≥8 and 11 times the recommended dose in man). Systemic exposure at these doses was higher in monkey but lower in rat than that obtained in man.
A no-effect level of 40 mg/kg/day was established in reproduction toxicity studies in the rat (for combination of cetirizine and pseudoephedrine at the ratio 5:120 w/w). Due to the low level of systemic exposure obtained in this species, these results cannot be considered as demonstrating the safety of use in pregnant and breast-feeding women.
The combination cetirizine/pseudoephedrine is neither mutagenic nor clastogenic and therefore unlikely to present a carcinogenic risk for humans.
