Rupatadine does not potentiate the CNS depressant effects of lorazepam: randomized, double-blind, crossover, repeated dose, placebo-controlled study

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Although one defining characteristic of second generation H1-antihistamines is their lack of CNS effects, it has been proved that some compounds of this group are not devoid of such effects. • There is evidence that second generation H1-antihistamine compounds without relevant CNS effects at therapeutic doses could increase the behavioural impairment produced by sedating drugs when both are taken concomitantly. • The evaluation of possible drug interactions is crucial, especially when both compounds could have CNS effects, due to the possible consequences at the patient safety level. WHAT THIS STUDY ADDS • The study demonstrates the lack of CNS effects after repeated administration at therapeutic doses of the unique second generation H1-antihistamine with anti-PAF activity. • The study demonstrates the lack of interaction between repeated administration of rupatadine 10 mg and a single oral dose of lorazepam 2 mg. • The study presents a useful design to evaluate the interaction between two compounds saving time and the exposure of the volunteers to medication. AIM The main objective was to assess whether benzodiazepine intake when rupatadine plasma concentrations were at steady-state would increase the CNS depressant effects. Rupatadine is a new H1-antihistamine which also inhibits platelet activating factor (PAF) release and has been shown to be clinically effective at doses of 10 mg. METHODS Sixteen healthy young volunteers took part in a crossover, randomized, double-blind, placebo controlled trial comprising two experimental periods (repeated administration for 7 days of rupatadine 10 mg or placebo as single oral daily doses, separated by a washout of 14 days). On days 5 and 7, according to a fully balanced design, a single oral dose of lorazepam 2 mg or placebo was added. CNS effects were evaluated on these days by seven objective tests of psychomotor performance and eight subjective visual analogue scales (VAS) at pre-dose and several times after drug intake. Four treatment conditions were evaluated: placebo, rupatadine 10 mg, lorazepam 2 mg and rupatadine 10 mg + lorazepam 2 mg. RESULTS Significant CNS effects, either impairment of psychomotor performance or subjective sedation, were observed when lorazepam was administered, either alone or in combination with steady state concentrations of rupatadine. No significant differences were found between these two conditions. In addition, rupatadine was not different from placebo. All treatments were well tolerated. CONCLUSION Repeated doses of rupatadine (10 mg orally) did not enhance the CNS depressant effects of lorazepam (2 mg orally, single dose) either in objective psychomotor tasks or in subjective evaluations.