Efficacy and tolerability of a fixed combination of cinnarizine and dimenhydrinate in treatment of vertigo - Analysis of data from five randomised, double-blind clinical studies

Objective: The purpose of the present analysis of a series of controlled cl inical studies was to evaluate the efficacy and tolerability of the fixed-c ombination preparation Arlevert(R) (ARL; cinnarizine 20 mg/dimenhydrinate 4 0 mg) in the treatment of central, peripheral or combined central/periphera l vestibular vertigo. Participants: Six hundred and thirty-five patients participated in five ran domised, double-blind, active- and/or placebo-controlled clinical studies c arried out in nine European clinics. Interventions: The patients received one of the following treatments three times daily for-C weeks, according to randomisation: ARL, cinnarizine 20 mg (CZ 20), cinnarizine 50 mg (CZ 50), dimenhydrinate 40 mg (DH 40), dimenhyd rinate 100 mg (DH 100), betahistine 12 mg (BH) or placebo. Results: After 4 weeks' treatment, the fixed-combination ARL led to statist ically significantly better improvements in vertigo symptoms (the primary e fficacy 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 dosa ge (p < 0.001 vs both CZ 50 and DH 100); ARL was also significantly more ef fective 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 v s all), DH 40 (p = 0.027) and BH (p = 0.039). ARL also markedly reduced veg etative concomitant symptoms. Across treatment groups, 70 to 98% of the pat ients judged the tolerability as 'good' or 'very good' (ARL = 90.3%). The r ate of adverse events with ARL was similar to or lower than that with the s tandard treatments. Reported adverse events corresponded to those already r ecognised for each drug. No serious adverse events were observed. Conclusion: The analysis demonstrates that the fixed combination of cinnari zine 20 mg and dimenhydrinate 40 mg 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 compari son with its active constituents given alone, as well as compared with the standard monotherapies using CZ 50, DH 100 and BH, the fixed-combination AR L can be considered as a first-line treatment option for vertigo.