RIVASTIGMINE - A REVIEW OF ITS USE IN ALZHEIMERS-DISEASE

Rivastigmine (SDZ ENA 713) is a carbamylating, long-acting reversible and noncompetitive carbamate acetylcholinesterase inhibitor that is in dicated as an oral treatment for patients with mild to moderately seve re Alzheimer's disease. The drug has been evaluated for this use in 3 well designed, adequately powered, phase II/III, 26-week clinical tria ls that included a total of 1479 rivastigmine and 647 placebo recipien ts. Most of these patients had concomitant disorders that were being t reated with numerous other drugs. Individual and pooled results of the se trials indicate that rivastigmine 6 to 12 mg/day usually produces c ognitive, global and functional changes that indicate significantly le ss deterioration than was observed with placebo in patients with mild to moderately severe Alzheimer's disease. Individual results of the 2 pivotal trials and pooled analysis also show that, compared with place bo recipients, significantly more rivastigmine 6 to 12 mg/day recipien ts respond to therapy. Indeed, after 26 weeks of therapy in the 2 pivo tal trials, significantly more rivastigmine 6 to 12 mg/day than placeb o recipients achieved clinically meaningful improvements as defined by 3 separate response criteria. The lower dosage range of 1 to 4 mg/day was not as effective as 6 to 12 mg/day, as measured using these crite ria and other efficacy parameters. Rivastigmine causes adverse events that are generally those expected from an acetylcholinesterase inhibit or. They are usually mild to moderate, of short duration and responsiv e to dosage reduction. Unpublished data from 3989 patients indicate th at rivastigmine and placebo were associated with similar incidences of serious adverse events and changes in laboratory parameters, ECG and cardiorespiratory vital signs. The most common events were gastrointes tinal, central and peripheral nervous system and whole body adverse ev ents. However, compared with placebo, rivastigmine more commonly cause d adverse events resulting in treatment withdrawal. These events were most frequently gastrointestinal and were more common in women. Conclu sion: Rivastigmine is a useful option for the treatment of patients wi th mild to moderately severe Alzheimer's disease. Although only short term (6-month) comparisons with placebo are available, given the lack of established treatment options it should be considered for first-lin e use in this population.