Rupatadine

Rupatadine (Rupafin®, Rinialer®, Rupax®, Alergoliber®) is a selective oral histamine H₁-receptor antagonist that has also been shown to have platelet-activating factor (PAF) antagonist activity in vitro. It is indicated for use in seasonal allergic rhinitis (SAR), perennial allergic rhinitis (PAR) and chronic idiopathic urticaria (CIU) in patients aged ≥12 years.

Clinical trials show that rupatadine is an effective and generally well tolerated treatment for allergic rhinitis and CIU. It has a rapid onset of action and a prolonged duration of activity. Importantly, it has no significant effect on cognition, psychomotor function or the cardiovascular system. Once-daily rupatadine significantly improves allergic rhinitis symptoms in patients with SAR, PAR or persistent allergic rhinitis (PER) compared with placebo, and provides similar symptom control to that of loratadine, desloratadine, cetirizine or ebastine. In patients with CIU, longer-term use of rupatadine improves CIU symptoms to a greater extent than placebo. It is as well tolerated as other commonly used secondgeneration H₁-receptor antagonists. Thus, the introduction of rupatadine extends the range of oral agents available for the treatment of allergic disorders, including allergic rhinitis and CIU.

Rupatadine shows a similar in vitro affinity for the H₁ receptor to loratadine and terfenadine and, like loratadine, is selective for peripheral over central H₁ receptors. The drug also demonstrates in vitro affinity for the PAF receptor. The antihistaminic activity and/or anti-inflammatory properties of rupatadine in in vitro studies and in animal models were similar to or greater than those of cetirizine, loratadine, desloratadine, levocabastine or terfenadine. However, unlike these H₁ antihistamines, rupatadine also showed specific PAF antagonist activity in vitro and in animal models. In patients with SAR, rupatadine reduced nasal and non-nasal allergen-induced symptoms in an allergen challenge chamber study, and in healthy volunteers, inhibited histamine-induced flare responses. Rupatadine has no clinically relevant effects on the cardiovascular system (in a ‘thorough QT/QTc study’ the risk of QT/QTc prolongation was not increased at rupatadine dosages 10 times the usual dosage in healthy volunteers), cognitive function or psychomotor function.

Rupatadine is rapidly absorbed after oral administration; peak plasma concentrations are achieved within =1 hour and steady state within 3–5 days. Rupatadine is highly protein bound (98–99%) and is well distributed in tissues. It undergoes extensive presystemic hepatic metabolism, predominantly via the cytochrome P450 (CYP) isoenzyme CYP3A4 and is excreted mainly in the bile. Some metabolites are active (e.g. desloratadine and its hydroxylate metabolites) and may contribute to the overall efficacy and long duration of activity of rupatadine. Significant drug interactions between rupatadine and some agents that inhibit CYP3A4 activity occur (e.g. ketoconazole, erythromycin, grapefruit juice) and coadministration of the drug with these agents is not recommended.

Several randomised, placebo- and/or active comparator-controlled trials have shown that rupatadine is effective in improving symptoms in adult or adolescent patients with allergic rhinitis or CIU. In these trials, rupatadine was superior to placebo, showed similar efficacy to loratadine, desloratadine and cetirizine, and was at least as effective as ebastine in reducing allergic symptoms in patients with SAR. Likewise, the drug was also superior to placebo and as effective as loratadine, ebastine or cetirizine in patients with PAR. In patients with PER, rupatadine, but not cetirizine, was superior to placebo at improving allergic symptoms and health-related quality of life (HR-QOL) was improved to a similar extent with rupatadine or cetirizine and to a greater extent than with placebo. Improvements in HR-QOL with rupatadine that were evident in the 4-week double-blind, placebo-controlled phase of another study in patients with PER were maintained for up to 1 year in the open label extension phase. Rupatadine was superior to placebo in improving symptoms of urticaria in patients with CIU; this benefit was evident from the first week of treatment and was maintained throughout a 6-week trial.

Rupatadine was generally well tolerated in clinical trials. A pooled analysis of data from clinical trials indicated that the most common adverse events with rupatadine were somnolence (9.5%), headache (6.8%), fatigue (3.2%), asthenia (1.5%) and dry mouth (1.2%). The majority of adverse events were of mild or moderate severity and there was no significant difference in the overall incidence of adverse events between rupatadine, the active comparators or placebo. The good tolerability of rupatadine was confirmed in a 1-year tolerability study in which the most common adverse event was somnolence (5.8%); headache and dry mouth were each reported by 0.83% of patients.