Safety/Tolerability and efficacy of rivastigmine in taiwanese patients with Alzheimer's disease: a prospective post-marketing surveillance study.

BACKGROUND AND OBJECTIVES: Rivastigmine is approved for the symptomatic treatment of mild to moderate dementia in patients with Alzheimer's disease. The drug was launched in Taiwan in 2000. The primary objective of this post-marketing surveillance (PMS) study was to describe the safety/tolerability of treatment with rivastigmine capsules in patients with Alzheimer's disease. The secondary objectives of this study were to define the optimal titration pattern, maintenance dose, efficacy and patient satisfaction with treatment with rivastigmine capsules.
METHODS: This was a prospective, non-interventional post-marketing observational study in patients who met the criteria for mild or moderate Alzheimer's disease. The primary outcome measure for this trial was the incidence of emerging adverse events. Dosages related to titration patterns and maintenance doses were summarized. Efficacy evaluations conducted using the Mini-Mental State Examination, Clinical Dementia Rating and modified Instrumental Activities of Daily Living scales were also primary outcome measures, and results are shown descriptively. The patients' therapeutic responses to rivastigmine and satisfaction with rivastigmine were secondary outcome measures. Therapeutic response and treatment satisfaction were summarized descriptively.
RESULTS: A total of 264 patients were enrolled into the study. The mean duration of exposure to rivastigmine during the study was 151.1 days. Patients were taking rivastigmine 1.5-6 mg twice daily and the most frequent maintenance dose level was 4.5 mg twice daily. Among patients treated with rivastigmine, all primary and secondary outcome measures showed improvement or stabilization of cognition and global functioning. Of the 253 safety analysis patients, 155 patients (61.3%) reported at least one adverse event. The most frequent adverse events by system organ class were psychiatric disorders (9.1%) and gastrointestinal disorders (8.3%). The most common adverse events observed were dizziness (5.5%), insomnia (5.1%), anorexia (4.0%) and gastrointestinal symptoms such as constipation (4.0%), vomiting (4.0%) and nausea (3.6%). These symptoms were mild in severity. A total of 12 patients (4.7%) reported 16 serious adverse events, including two deaths, three fractures, three behavioural and psychological symptoms of dementia, one syncope with head trauma, one peptic ulcer, and six other hospitalizations. None were reported to be related to rivastigmine.
CONCLUSIONS: Based on the results of this study, rivastigmine administered usually at a dose of 3-6 mg twice daily was found to be well tolerated. Although the rate of adverse events was high, the majority of these symptoms were mild in severity and short in duration. This study also demonstrated the efficacy of rivastigmine in at least stabilizing the symptoms of Alzheimer's disease.