P1‐444: Assessing skin tolerability due to the change in the mode of administration of rivastigmine (oral to transdermal) according to two different strategies in Alzheimer patients

Recently available transdermal rivastigmine patches for the treatment of Alzheimer disease (AD) may present benefits over capsules due to sustained drug penetration through skin, good local tolerability and minimized gastrointestinal (GI) problems. Additional data are needed regarding convenience of change from oral to transdermal treatment. This study has been designed to evaluate skin and GI tolerability and the need for titration to reach optimal doses of transdermal rivastigmine patches in AD patients switching from oral administration. A multicenter, randomized, open-label study including 142 patients with mild-to-moderate AD (DSM-IV) previously treated with rivastigmine capsules (6-12 mg/day) was designed. Patients were randomized to: continue with capsules (RC group) for 3 months (n = 51); switch to rivastigmine patch (RP) 9.5 mg/day for 3 months (n = 48) (no titration RP); or switch to RP 4.6 mg/day for 1 month followed by 9.5 mg/day for 2 months (n = 43) (titration RP). Main endpoints considered were the incidence of skin and GI adverse events (AEs) during the study. No significant differences were detected between the two groups treated with patches in the percentage of patients with adverse events involving the skin (11.6% and 17.3% in no titration and titration RP groups, p = 0.467). No severe AEs were reported (of any type) and only 2% of retirements. Main skin AEs in RP groups were: erythema (7% titration vs 10.6% no titration RP), pruritus (0% titration vs 6.4% no titration RP) and urticaria (2.3% tritation vs 2.1% no titration RP). Incidences of GI AEs (diarrhea, nausea or vomiting) during the study were 6.1%, 4.3% and 4.7% for the RC, no titration RP and titration RP groups, respectively (p = 0.908). No differences between arms were observed in the incidences of AEs (of any nature) from randomisation to month 1 (p = 0.821) nor from month 1 to the end of the study (p = 0.697). Oral rivastigmine treatments may be switched to 9.5 mg/day patches without need for titration, despite pruritus effects tend to be avoided with a titration phase. Moreover, changing the mode of administration for rivastigmine (from capsules to patches) results in a better GI tolerability in AD patients.