Source: Marketing Authorisation Holder Revision Year: 2021 Publisher: Manufacturer tablets: UCB Farchim S.A., Z.I. de Planchy, 10 Chemin de Croix Blanche, CH-1630 Bulle, Switzerland Packager: Aesica Pharmaceuticals S.r.l., Via Praglia 15, I 10044 Pianezza, Italy
Pharmacotherapeutic group: Nasal decongestants for systemic use
ATC Code: R01BA52
The pharmacodynamic activitiy of cetirizine-pseudoephedrine is directly related to the additive effect of the action of its constituents.
Cetirizine is a potent and selective antagonist of the H1-receptor with anti-allergic properties; it inhibits the early phase of the histamine-related allergic reaction; in addition it reduces the migration of some type of inflammatory cells and the release of mediators associated with the late allergic response; it inhibits the reactions induced by histamine and pollens in nasal provocative tests.
Pseudoephedrine, a stereoisomer of ephedrine, is an orally active sympathomimetic, whose alphamimetic effects are greater than its beta-mimetic activity; due to its vasoconstrictor action, it has a decongestant effect on the nasal mucosa.
Not relevant for this product.
There was no evidence for a relevant pharmacokinetic interaction between cetirizine and pseudoephedrine.
After oral administration, cetirizine is rapidly and almost completely absorbed. Peak plasma concentrations are generally obtained within 1 hour under fasting conditions. The absorption is independent of the dose.
Inter- and intra-subjects variations are low.
Cetirizine is highly bound to plasma proteins (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.
Cetirizine does not undergo any appreciable first pass metabolism. The plasma half-life of cetirizine is approximately 9 hours. This value is increased in patients with reduced renal function. After repeated oral administration, the daily urinary excretion of unchanged cetirizine is approximately 65 % of the dose. The elimination is independent of the dose.
It is excreted mainly unchanged in the urine. The rate of urinary excretion is increased when the pH of urine is reduced, and reduced in case of alkalinization of urine. After repeated oral administration (every 12 hours), at steady-state, the apparent elimination half-life is estimated to be approximately 9 hours.
The dose should be reduced to half the usual recommended dose.
Not relevant for this product.Animal studies have shown no toxic doses equal or higher than 30 mg/kg/day in rats and 40 mg/kg/day in the Cynomolgus monkey (≥8 and 11 times the recommended dose in humans). The systemic exposure to these doses was higher in the monkey but lower in rats, compared to that obtained in humans. There are no carcinogenicity studies of pseudoephedrine in combination with cetirizine. The combination cetirizine/pseudoephedrine is neither mutagenic nor clastogenic. Reproduction toxicology studies in male and female rats using oral doses up to 160 mg/kg/day (containing 6.4 mg/kg cetirizine and 153.6 mg/kg pseudoephedrine, 1:24), producing systemic exposure to cetirizine 2- to 3-fold higher than the therapeutic exposure in humans, have shown no effects at a dose of 40 mg/kg/day. Due to the low levels of systemic exposure in these species, these results cannot be considered significant to demonstrate a safe use in pregnant and lactating women.
At higher doses of 160 mg/kg/day, no teratogenic effects were observed, but effects on the mother and offspring were seen (total or partial loss of the litter, reduced growth of the offspring, delayed general development) (see Section Pregnancy and Lactation).
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