Safety and tolerability of rivastigmine capsule with memantine in patients with probable Alzheimer's disease: a 26-week, open-label, prospective trial (Study ENA713B US32)

Objective: Rivastigmine, a dual cholinesterase inhibitor (ChEI), is widely approved for the symptomatic treatment of both mild-to-moderate Alzheimer's disease (AD) and Parkinson's disease dementia. Orally administered ChEIs may be associated with gastrointestinal (GI) side effects and add-on therapy with memantine, an N-methyl-p-aspartate receptor antagonist, approved for moderate-to-severe AD, may ameliorate such side effects. This was a 26-week, prospective, multicenter, single-arm, open-label pilot study to assess the safety and tolerability of rivastigmine capsules plus memantine in patients with moderate AD. Methods: The primary objective was to assess the safety and tolerability of rivastigmine capsules 6-12 mg/day plus memantine (5-20 mg/day) as measured by the incidences of vomiting and nausea compared with those reported in the rivastigmine United States Prescribing Information (US PI). A total of 117 patients were enrolled with 116 receiving at least one dose of study medication. Results: The incidences of nausea and vomiting (30% and 13%, respectively) observed in patients who received 6-12 mg/day rivastigmine plus memantine were lower than those stated in the US PI for rivastigmine monotherapy 6-12 mg/day (47% and 31%, respectively). The most common adverse events were nausea, vomiting, and dizziness. Conclusion: Results from this study suggest the combination of rivastigmine capsule and memantine in patients with moderate AD is safe and tolerable. Improved GI tolerability of rivastigmine has been established with rivastigmine transdermal patch. Copyright (C) 2009 John Wiley & Sons, Ltd.