Galantamineside effects

Serious adverse reactions are discussed in more detail in the following sections of the labeling: Serious Skin Reactions Cardiovascular Conditions Gastrointestinal Conditions Genitourinary Conditions Neurological Conditions Pulmonary Conditions Deaths in Patients with Mild Cognitive Impairment (MCI) The most common adverse reactions (≥5%) were nausea, vomiting, diarrhea, dizziness, headache, and decreased appetite 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 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