Thus, tacrine is not a convenient drug to prescribe or take, regardless of its efficacy. Also, the variations in the clinical trial designs made it difficult to fully explore the prevalence of other side effects. Donepezil The most common gastrointestinal side effects of donepezil include nausea, vomiting, diarrhea, and anorexia. Additionally, some patients developed muscle cramps, headache, dizziness, syncope, or flushing. Hematological side effects include anemia, thrombocytopenia and eosinophilia. Cardiac effects included bradyarrhythmia, and syncope. CNS effects included headache, dizziness, insomnia, weakness, drowsiness, fatigue, and agitation. Inhibitors,research,lifescience,medical Weight loss occurred

at twice the rate of placebo in the nursing home study, but was not reported in the other trials. Cholinergically-related adverse effects show a dose response. Adverse effects led to withdrawal from the 24week study in 16% of patients in the 10-mg group, 6% of patients in the 5-mg group, and Inhibitors,research,lifescience,medical 5% in the placebo group.16 Adverse effects occurred at. a. higher Inhibitors,research,lifescience,medical rate when the titration from 5 mg to 10 mg was made in 1 week compared with 6 weeks. Metrifonate As evidenced by the proportion of patients completing trials (Table II) metrifonate was generally well tolerated over periods of 6 months or less; the tolerability over longer periods is not known. Metrifonate is similarly or better tolerated

than other ChEIs in that the vast, majority of metrifonate-treated Inhibitors,research,lifescience,medical patients enrolled in phase 3 studies complete these

clinical trials, and cholinergic adverse events were reported as frequently or less, compared with patients in other ChEJ. trials. LY411575 Significant side effects occur in no more Inhibitors,research,lifescience,medical than 11 % or so of patients receiving higher doses. The most, commonly reported adverse events include diarrhea, nausea, abdominal pain, leg cramps, and rhinitis. Leg cramps occur in 7% to 10% of patients, and 3 to 10 times more frequently than with placebo. The most obvious reason for this is tonic stimulation of myoneural nicotinic receptors. Increased incidence of leg or muscle cramping has been reported with other ChEIs as well. The statistically significant decrease in heart rate of about 5 to 9 beats per minute (bpm) at higher doses of medication is likely due to vagotonic effects observed with some ChEIs, and might be of clinical concern. The extent Oxygenase of clinically significant bradycardia (eg, heart rate <50 bpm) was reported in only one trial, and was 7% and 32 times more frequent than with placebo. Of significant concern, however, is that approximately 20 patients out of 3000 in the metrifonate clinical studies developed “asthenia, myasthenia, and malaise,” and “4 patients with muscular weakness received respiratory support. ” (Letter from Bayer Pharmaceuticals, September 18, 1998.