Galantamine hydrobromide extended-release capsules are contraindicated in patients with known hypersensitivity to galantamine hydrobromide or to any excipients used in the formulation. Known hypersensitivity to galantamine hydrobromide or any excipients ( 4 )
AND PRECAUTIONS Serious skin reactions: discontinue at first appearance of skin rash (5.1) All patients should be considered at risk for adverse effects on cardiac conduction, including bradycardia and AV block, due to vagotonic effects on sinoatrial and atrioventricular nodes (5.3) Active or occult gastrointestinal bleeding: monitor, especially those with an increased risk for developing ulcers (5.4) Cholinomimetics may cause bladder outflow obstruction (5.5) Monitor for respiratory adverse events in patients with a history of severe asthma or obstructive pulmonary disease (5.7)
5.1 Serious Skin Reactions Serious skin reactions (Stevens-Johnson syndrome and acute generalized exanthematous pustulosis) have been reported in patients receiving galantamine extended-release capsules and galantamine tablets. Inform patients and caregivers that the use of galantamine extended-release capsules should be discontinued at the first appearance of a skin rash, unless the rash is clearly not drug-related. If signs or symptoms suggest a serious skin reaction, use of this drug should not be resumed and alternative therapy should be considered.
5.2 Anesthesia Galantamine, as a cholinesterase inhibitor, is likely to exaggerate the neuromuscular blocking effects of succinylcholine-type and similar neuromuscular blocking agents during anesthesia.
5.3 Cardiovascular Conditions Because of their pharmacological action, cholinesterase inhibitors have vagotonic effects on the sinoatrial and atrioventricular nodes, leading to bradycardia and AV block. Bradycardia and all types of heart block have been reported in patients both with and without known underlying cardiac conduction abnormalities <span class="opacity-50 text-xs">[see Adverse Reactions (6.1 , 6.2) ]</span> . Therefore, all patients should be considered at risk for adverse effects on cardiac conduction. 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 twice daily 0.4% [3/692]; 8 mg twice daily 1.3% [7/552]; 12 mg twice daily 2.2% [6/273]).
5.4 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 have shown no increase, relative to placebo, in the incidence of either peptic ulcer disease or gastrointestinal bleeding. Galantamine, as a predictable consequence of its pharmacological properties, has been shown to produce nausea, vomiting, diarrhea, anorexia, and weight loss. During therapy with galantamine extended-release capsules, the patient’s weight should be monitored.
5.5 Genitourinary Conditions Although this was not observed in clinical trials with galantamine, cholinomimetics may cause bladder outflow obstruction.
5.6 Neurological Conditions Cholinesterase inhibitors are believed to have some potential to cause generalized convulsions <span class="opacity-50 text-xs">[see Adverse Reactions (6.2) ]</span> . Seizure activity may also be a manifestation of Alzheimer’s disease. Patients with Alzheimer’s disease should be monitored closely for seizures while taking galantamine extended-release capsules. An increase in cholinergic tone may worsen symptoms related to extrapyramidal disorders <span class="opacity-50 text-xs">[see Adverse Reactions (6.2) ]</span> .
5.7 Pulmonary Conditions Because of its cholinomimetic action, galantamine extended-release capsules should be prescribed with care to patients with a history of severe asthma or obstructive pulmonary disease. Respiratory function should be monitored closely for the occurrence of respiratory adverse effects.
5.8 Deaths in Patients with Mild Cognitive Impairment (MCI) In two randomized placebo-controlled trials of 2 years duration in patients with mild cognitive impairment (MCI), a total of 13 patients on galantamine (n=1026) and 1 patient on placebo (n=1022) died. The deaths were due to various causes which could be expected in an elderly population; about half of the galantamine deaths appeared to result from various vascular causes (myocardial infarction, stroke, and sudden death). Although the difference in mortality between galantamine- and placebo-treated groups in these two studies was significant, the results are highly discrepant with other studies of galantamine. Specifically, in these two MCI studies, the mortality rate in the placebo-treated patients was markedly lower than the rate in placebo-treated patients in trials of galantamine in Alzheimer’s disease or other dementias (0.7 per 1000 person years compared to 22 to 61 per 1000 person years, respectively). Although the mortality rate in the galantamine-treated MCI patients was also lower than that observed in galantamine-treated patients in Alzheimer’s disease and other dementia trials (10.2 per 1000 person years compared to 23 to 31 per 1000 person years, respectively), the relative difference was much less. When the Alzheimer’s disease and other dementia studies were pooled (n=6000), the mortality rate in the placebo group numerically exceeded that in the galantamine group. Furthermore, in the MCI studies, no patients in the placebo group died after 6 months, a highly unexpected finding in this population. Individuals with mild cognitive impairment demonstrate isolated memory impairment greater than expected for their age and education, but do not meet current diagnostic criteria for Alzheimer’s disease.