Because of their pharmacologic action, cholinesterase inhibitors have vagotonic effects on the sinoatrial (SA) and atrioventrical (AV) nodes, leading to bradycardia and AV block. These actions may be particularly important to patients with superventricular cardiac conduction disorders, or to patients taking other drugs concomitantly that significantly slow heart rate. In clinical trials, galantamine HBr was associated with more frequent reports of bradycardia and syncope vs placebo. Post marketed surveillance of marketed anticholinesterase inhibitors has shown that bradycardia and all types of heart block have been reported in patients both with and without known underlying cardiac conduction abnormalities. All patients should be considered at risk for adverse effects on cardiac conduction.
Cholinesterase inhibitors may increase gastric acid secretion. Patients should be monitored closely for symptoms of active or occult gastrointestinal bleeding, especially those with an increased risk of developing ulcers, eg, those with a history of ulcer disease or patients using concurrent nonsteroidal anti-inflammatory drugs.Genitourinary Cholinesterase inhibitors may cause bladder outflow obstruction. Neurological conditions Cholinesterase inhibitors are believed to have some potential to cause generalized convulsions. Seizure activity may also be a manifestation of Alzheimer's disease. In clinical trials, there was no increase in the incidence of convulsions with galantamine HBr compared with placebo. Pulmonary conditions Cholinesterase inhibitors should be prescribed with care to patients with a history of asthma or obstructive pulmonary disease. Deaths in subjects with mild cognitive impairment (MCI) In controlled trials in elderly subjects with MCI, 13 subjects on RAZADYNE ® (n=1026) and 1 subject on placebo (n=1022) died of various causes. About half of the RAZADYNE ® deaths appeared to result from various vascular causes (myocardial infarction, stroke, and sudden death). RAZADYNE ® and RAZADYNE ® ER are not indicated for the treatment of MCI. Hepatic or renal impairment In patients with moderately impaired hepatic or renal function, dose titration should proceed cautiously. The use of RAZADYNE ® or RAZADYNE ® ER in patients with severe hepatic impairment or severely impaired renal function (Cl cr < 9 mL/min) is not recommended. Most common Adverse Events The most common adverse events in clinical studies occurring at rate of at least 5% and at least twice that of placebo at the recommended maintenance dose of either 16 or 24 mg/day under conditions of every 4 week dose escalation for each 8-mg increase were nausea, vomiting, diarrhea, anorexia, and weight decrease.