Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2021 Publisher: Opella Healthcare UK Limited, trading as Sanofi, 410 Thames Valley Park Drive, Reading, Berkshire, RG6 1PT, UK
Antihistamines for systemic use
ATC code: R06AX25
Mizolastine possesses antihistamine and antiallergic properties due to a specific and selective antagonism of peripheral histamine H1 receptors. It has also been shown to inhibit histamine release from mast cells (at 0.3 mg/kg orally) and the migration of neutrophils (at 3 mg/kg orally) in animal models of allergic reactions.
In man, histamine-induced wheal and flare studies have shown that mizolastine 10 mg is a rapid, potent (80% inhibition after 4 hrs) and sustained (24hr) antihistamine. No tachyphylaxis occurred after long-term administration.
In both preclinical and clinical studies, no anticholinergic effect has been demonstrated.
Following oral administration mizolastine is rapidly absorbed. Peak plasma concentration is reached at a median time of 1.5 hours.
Bioavailability is 65% and linear kinetics have been demonstrated.
The mean elimination half-life is 13.0 hours with plasma protein binding of 98.4%.
In hepatic insufficiency the absorption of mizolastine is slower and the distribution phase longer, with a resulting moderate increase in AUC of 50%.
The principal metabolic pathway is glucuronidation of the parent compound. The cytochrome P450 3A4 enzyme system is involved in one of the additional metabolic pathways with formation of the hydroxylated metabolites of mizolastine. None of the identified metabolites contribute to the pharmacological activity of mizolastine.
An increase in mizolastine plasma levels, observed with systemic ketoconazole and erythromycin, led to concentrations equivalent to those obtained after a 15 to 20 mg dose of mizolastine alone.
In studies carried out in healthy volunteers, no clinically significant interaction has been recorded with food, warfarin, digoxin, theophylline, lorazepam, or diltiazem.
Pharmacological studies in several species have shown an effect on cardiac repolarisation at doses in excess of 10-20 times the therapeutic dose. In conscious dogs, mizolastine has shown pharmacological interactions with ketoconazole at the electrocardiographic level at 70 times the therapeutic dose.
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