Generic: GALANTAMINE HYDROBROMIDE
1 INDICATIONS AND USAGE Galantamine hydrobromide extended-release capsules are indicated for the treatment of mild to moderate dementia of the Alzheimer's type. Galantamine hydrobromide is a cholinesterase inhibitor indicated for the treatment of mild to moderate dementia of the Alzheimer’s type ( 1 )
5 WARNINGS 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 resp...
5 WARNINGS 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 hydrobromide extended-release capsules. Inform patients and caregivers that the use of galantamine 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 [see Adverse Reactions (6.1, 6.2)] . 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, 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 [see Adverse Reactions (6.2)]. 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 hydrobromide extended-release capsules. An increase in cholinergic tone may worsen symptoms related to extrapyramidal disorders [see Adverse Reactions (6.2)]. 5.7 Pulmonary Conditions Because of its cholinomimetic action, galantamine hydrobromide 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=1,026) and 1 patient on placebo (n=1,022) 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 1,000 person years compared to 22 to 61 per 1,000 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 1,000 person years compared to 23 to 31 per 1,000 person years, respectively), the relative difference was much less. When the Alzheimer’s disease and other dementia studies were pooled (n=6,000), 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.
6 ADVERSE REACTIONS Serious adverse reactions are discussed in more detail in the following sections of the labeling: Serious Skin Reactions [see Warnings and Precautions ( 5.1 )] Cardiovascular Conditions [see Warnings and Precautions ( 5.3 )] Gastrointestinal Conditions [see Warnings and Precautions ( 5.4 )] Genitourinary Conditions [see Warnings and Precautions ( 5.5 )] Neurological Conditions [see Warnings and Precautions ( 5.6 )] Pulmonary Conditions [see Warnings and Precautions ( 5.7 )] D...
6 ADVERSE REACTIONS Serious adverse reactions are discussed in more detail in the following sections of the labeling: Serious Skin Reactions [see Warnings and Precautions ( 5.1 )] Cardiovascular Conditions [see Warnings and Precautions ( 5.3 )] Gastrointestinal Conditions [see Warnings and Precautions ( 5.4 )] Genitourinary Conditions [see Warnings and Precautions ( 5.5 )] Neurological Conditions [see Warnings and Precautions ( 5.6 )] Pulmonary Conditions [see Warnings and Precautions ( 5.7 )] Deaths in Patients with Mild Cognitive Impairment (MCI) [see Warnings and Precautions ( 5.8 )] The most common adverse reactions (≥5%) were nausea, vomiting, diarrhea, dizziness, headache, and decreased appetite ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Sun Pharmaceutical Industries, Inc. at 1-800-818-4555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The most common adverse reactions (≥5%) in galantamine-treated patients from double-blind clinical trials were nausea, vomiting, diarrhea, dizziness, headache, and decreased appetite. The most common adverse reactions associated with discontinuation (≥1%) in galantamine-treated patients from double-blind clinical trials were nausea (6.2%), vomiting (3.3%), decreased appetite (1.5%), and dizziness (1.3%). The safety of the extended-release capsule and immediate-release tablet formulations of galantamine was evaluated in 3,956 galantamine-treated patients who participated in 8 placebo-controlled clinical studies and 1,454 patients in 5 open-label clinical studies with mild to moderate dementia of the Alzheimer’s type. In clinical studies, the safety profile of once-daily treatment with extended-release galantamine was similar in frequency and nature to that seen with tablets. The information presented in this section was derived from pooled double-blind studies and from pooled open-label data. Commonly-Observed Adverse Reactions in Double-Blind, Placebo-Controlled Clinical Trials Table 1 lists the adverse reactions reported in ≥1% of galantamine-treated patients in 8 placebo-controlled, double-blind clinical trials. Table 1. Adverse Reactions Reported by ≥1% of Galantamine-Treated Patients in Pooled Placebo-Controlled, Double-Blind Clinical Trials System/Organ Class Adverse Reaction G alantamine (n=3,956) % Placebo (n=2,546) % Metabolism and Nutrition Disorders Decreased appetite 7.4 2.1 Psychiatric Disorders Depression 3.6 2.3 Nervous System Disorders Headache 7.1 5.5 Dizziness 7.5 3.4 Tremor 1.6 0.7 Somnolence 1.5 0.8 Syncope 1.4 0.6 Lethargy 1.3 0.4 Cardiac Disorders Bradycardia 1.0 0.3 Gastrointestinal Disorders Nausea 20.7 5.5 Vomiting 10.5 2.3 Diarrhea 7.4 4.9 Abdominal discomfort 2.1 0.7 Abdominal pain 3.8 2.0 Dyspepsia 1.5 1.0 Musculoskeletal and Connective Tissue Disorders Muscle spasms 1.2 0.5 General Disorders and Administration Site Conditions Fatigue 3.5 1.8 Asthenia 2.0 1.5 Malaise 1.1 0.5 Investigations Decreased weight 4.7 1.5 Injury, Poisoning and Procedural Complications Fall 3.9 3.0 Laceration 1.1 0.5 The majority of these adverse reactions occurred during the dose-escalation period. In those patients who experienced the most frequent adverse reaction, nausea, the median duration of the nausea was 5 to 7 days. Other Adverse Reactions Observed in Clinical Trials of Galantamine The following adverse reactions occurred in <1% of all galantamine-treated patients (N=3,956) in the above double-blind, placebo-controlled clinical trial data sets. In addition, the following also includes all adverse reactions reported at any frequency rate in patients (N=1,454) who participated in open-label studies. Adverse reactions listed in Table 1 above were not included below: Metabolism and Nutrition Disorders: Dehydration Nervous System Disorders: Dysgeusia, Hypersomnia, Paresthesia Eye Disorders: Blurred vision Cardiac Disorders: First degree atrioventricular block, Palpitations, Sinus bradycardia, Supraventricular extrasystoles Vascular Disorders: Flushing, Hypotension Gastrointestinal Disorders: Retching Skin and Subcutaneous Tissue Disorders: Hyperhidrosis Musculoskeletal and Connective Tissue Disorders: Muscular weakness Discontinuations Due to Adverse Reactions In the 8 placebo-controlled studies of adults, 418 (10.6%) galantamine-treated patients (N=3,956) and 56 (2.2%) placebo patients (N=2,546) discontinued due to an adverse reaction. Those events with an incidence of ≥0.5% in the galantamine-treated patients included nausea (245, 6.2%), vomiting (129, 3.3%), decreased appetite (60, 1.5%), dizziness (50, 1.3%), diarrhea (31, 0.8%), headache (29, 0.7%), and decreased weight (26, 0.7%). The only event with an incidence of ≥0.5% in placebo patients was nausea (17, 0.7%). In the 5 open-label studies, 103 (7.1%) patients (N=1,454) discontinued due to an adverse reaction. Those events with an incidence of ≥0.5% included nausea (43, 3.0%), vomiting (23, 1.6%), decreased appetite (13, 0.9%), headache (12, 0.8%), decreased weight (9, 0.6%), dizziness (8, 0.6%), and diarrhea (7, 0.5%). 6.2 Postmarketing Experience The following additional adverse reactions have been identified during post-approval use of galantamine hydrobromide extended-release capsules. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: Immune System Disorders: Hypersensitivity Psychiatric Disorders: Hallucinations Nervous System Disorders: Seizures, extrapyramidal disorder [see Warnings and Precautions (5.6)] Ear and Labyrinth Disorders: Tinnitus Cardiac Disorders: Complete atrioventricular block Vascular Disorders: Hypertension Hepatobiliary Disorders: Hepatitis, increased hepatic enzyme Skin and Subcutaneous Tissue Disorders: Stevens-Johnson syndrome, acute generalized exanthematous pustulosis, Erythema multiforme
Medical Disclaimer: This information is for educational purposes only and does not constitute medical advice. Always consult a licensed healthcare provider before making any decisions about your medications. Data sourced from openFDA.