Rivastigimine As with other ChEIs, side effects were primarily gastrointestinal and occurred in the

high-dose (6-12 mg/d) group. Side effects occurred primarily during dose escalation and led to withdrawal in one study in 23% of the high-dose group, 7% of the low-dose group, and 7% of the placebo group. Of note, inclusion criteria for these clinical Inhibitors,research,lifescience,medical trials allowed for patients with a broader range of medical comorbidities to be entered into these studies than into those with donepezil or tacrine, perhaps improving somewhat, the potential generalizability of the findings. Adverse effects that occurred with rivastigmine treatment are exemplified by findings in one study.25 Side effects that occurred in the 6- to 12-mg/day group at a level significantly greater than placebo during the titration phase were sweating, Inhibitors,research,lifescience,medical fatigue, asthenia,

weight loss, malaise, dizziness (24% vs 13% placebo), somnolence (9% vs 2% placebo), nausea (48% vs 11% placebo), vomiting (27% vs 11 % placebo), anorexia (20% vs 3% placebo), and flatulence. In the maintenance phase, dizziness Inhibitors,research,lifescience,medical (14% vs 4% placebo), nausea (20% vs 3% placebo), vomiting (16% vs 2% placebo), dyspepsia (5% vs 1% placebo), sinusitis (4% vs 1% placebo) occurred statistically more in the 6- to 12-mg/day group than in the placebo group. Reference to the FDA-approved prescribing information (April 2000) notes the higher than expected incidence of gastrointestinal disturbances printed in bold type (http://www.fda.edu.gov & http://www.novartis.com). The FDA approval letter requests that the sponsor of the medication perform further analyses to better characterize these effects. Galantamine Gastrointestinal side effects were among the most frequent adverse events in both groups and more common Inhibitors,research,lifescience,medical at the higher doses. As with some other ChEIs, the rate of discontinuation in the 5-month clinical

trial43 was about the same for galantamine-treated Inhibitors,research,lifescience,medical patients as for those receiving placebo (10% vs 7%). The main adverse events were: nausea (16.5%, 13.3%, and 4.5%), vomiting (9.9%, 6.1%, and 3.6%), anorexia (8.8%, 6.5%, and 3.1%), and diarrhea Cytidine deaminase (5.5%, 12.2%, and 5.9%), in the 24-mg/d, 16-mg/d, and placebo groups, respectively. Furthermore, there was a significant dose-related weight loss of greater than 7% of body weight in 11%, 6%, and 3.5% of patients in the groups defined above. Particular adverse events of MLN0128 ic50 concern Myasthenia or fatigue Myasthenia and respiratory depression were of particular concern with metrifonate, leading to its therapeutic demise. Although these might, be unique to the irreversible binding of metrifonate at the myoneural junction, it. could occur with other ChEIs as well. The number of instances was small, since myasthenia and respiratory depression occurred in only about. 20 patients out. of about 3000, yet. large enough to have a significant, public health impact.