that bradycardia and all types of heart block have been reported in patients both with and without known underlying cardiac conduction abnormalities. Therefore all patients should be considered at risk for adverse effects on cardiac conduction.
In randomized controlled trials, bradycardia was reported more frequently in galantamine-treated patients than in placebo-treated patients, but was rarely severe and rarely led to treatment discontinuation. The overall frequency of this event was 2 to 3% for galantamine doses up to 24 mg/day compared with <1% for placebo. No increased incidence of heart block was observed at the recommended doses.
Patients treated with galantamine up to 24 mg/day using the recommended dosing schedule showed a dose-related increase in risk of syncope (placebo 0.7% [2/286]; 4 mg BID 0.4% [3/692]; 8 mg BID 1.3% [7/552]; 12 mg BID 2.2% [6/273]).
Gastrointestinal Conditions
Through their primary action, cholinomimetics may be expected to increase gastric acid secretion due to increased cholinergic activity. Therefore, patients should be monitored closely for symptoms of active or occult gastrointestinal bleeding, especially those with an increased risk for developing ulcers, e.g., those with a history of ulcer disease or patients using concurrent nonsteroidal anti-inflammatory drugs (NSAIDS). Clinical studies of galantamine hydrobromide have shown no increase, relative to placebo, in the incidence of either peptic ulcer disease or gastrointestinal bleeding.
Galantamine hydrobromide, as a predictable consequence of its pharmacological properties, has been shown to produce nausea, vomiting, diarrhea, anorexia, and weight loss. (see ADVERSE REACTIONS).
Genitourinary
Although this was not observed in clinical trials with galantamine hydrobromide, cholinomimetics may cause bladder outflow obstruction.
Neurological Conditions
Seizures: Cholinesterase inhibitors are believed to have some potential to cause generalized convulsions. However, 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 hydrobromide compared to placebo.
Pulmonary Conditions
Because of its cholinomimetic action, galantamine should be prescribed with care to patients with a history of severe asthma or obstructive pulmonary disease.
PRECAUTIONS
Information for Patients and Caregivers:
Caregivers should be instructed about the recommended dosage and administration of galantamine hydrobromide. Galantamine hydrobromide extended-release capsules should be administered once daily in the morning, preferably with food (although not required). Dose escalation (dose increases) should follow a minimum of four weeks at prior dose.
Patients and caregivers should be advised that the most frequent adverse events associated with use of the drug can be minimized by following the recommended dosage and administration.
Patients and caregivers should be advised to ensure adequate fluid intake during treatment. If therapy has been interrupted for several days or longer, the patient should be restarted at the lowest dose and the dose escalated to the current dose.
Deaths in Subjects with Mild Cognitive Impairment (MCI)
In two randomized placebo controlled trials of 2 years duration in subjects with mild cognitive impairment (MCI), a total of 13 subjects on galantamine (n=1026) and 1 subjec |
