Efficacy and Tolerability of a Fixed Combination of Cinnarizine and Dimenhydrinate in Treatment of Vertigo

Abstract

Objective: The purpose of the present analysis of a series of controlled clinical studies was to evaluate the efficacy and tolerability of the fixed-combination preparation Arlevert® (ARL; cinnarizine 20mg/dimenhydrinate 40mg) in the treatment of central, peripheral or combined central/peripheral vestibular vertigo.

Participants: Six hundred and thirty-five patients participated in five randomised, double-blind, active-and/or placebo-controlled clinical studies carried out in nine European clinics.

Interventions: The patients received one of the following treatments three times daily for 4 weeks, according to randomisation: ARL, cinnarizine 20mg (CZ 20), cinnarizine 50mg (CZ 50), dimenhydrinate 40mg (DH 40), dimenhydrinate 100mg (DH 100), betahistine 12mg (BH) or placebo.

Results: After 4 weeks’ treatment, the fixed-combination ARL led to statistically significantly better improvements in vertigo symptoms (the primary efficacy variable) than monotherapy with its active constituents at the same dosage (p = 0.021 vs CZ 20; p = 0.018 vs DH 40) or at 2.5-fold higher dosage (p < 0.001 vs both CZ 50 and DH 100); ARL was also significantly more effective than BH and placebo (p < 0.001 vs both). Vestibulospinal testing by craniocorpography showed that ARL produced significantly greater decreases in lateral sway (Unterberger test) than CZ 50, DH 100, placebo (p < 0.001 vs all), DH 40 (p = 0.027) and BH (p = 0.039). ARL also markedly reduced vegetative concomitant symptoms. Across treatment groups, 70 to 98% of the patients judged the tolerability as ‘good’ or ‘very good’ (ARL = 90.3%). The rate of adverse events with ARL was similar to or lower than that with the standard treatments. Reported adverse events corresponded to those already recognised for each drug. No serious adverse events were observed.

Conclusion: The analysis demonstrates that the fixed combination of cinnarizine 20mg and dimenhydrinate 40mg given three times daily is an effective and well tolerated treatment for central, peripheral and combined central/peripheral vertigo. Because of a significantly superior efficacy in comparison with its active constituents given alone, as well as compared with the standard monotherapies using CZ 50, DH 100 and BH, the fixed-combination ARL can be considered as a first-line treatment option for vertigo.