Serious adverse reactions are discussed in more detail in the following sections of the labeling:
- Serious skin reactions [see WARNINGS AND PRECAUTIONS]
- Deaths in subjects with mild cognitive impairment (MCI) [see WARNINGS AND PRECAUTIONS]
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 in galantamine-treated patients from double-blind clinical trials ( ≥ 5%) were nausea, vomiting, diarrhea, dizziness, headache, decreased appetite, and weight decreased.
The most common adverse reactions associated with discontinuation ( ≥ 1%) in galantamine-treated patients from double-blind clinical trials were nausea (7.7%), vomiting (4.1%), decreased appetite (1.9%), and dizziness (1.6%).
The safety of the extended-release capsule and immediate-release tablet formulations of galantamine was evaluated in 2932 galantamine-treated patients who participated in 7 placebo-controlled clinical studies and 1454 subjects 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 7 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
|Metabolism and Nutrition Disorders|
|Nervous System Disorders|
|Upper abdominal pain||2.0||1.4|
|Skin and Subcutaneous Tissue Disorders|
|Musculoskeletal and Connective Tissue Disorders|
|General Disorders and Administration Site Conditions|
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 5-7 days.
Other Adverse Reactions Observed in Clinical Trials of Galantamine
The following adverse reactions occurred in < 1% of all galantamine-treated patients (N=2932) 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=1454) 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
Musculoskeletal and Connective Tissue Disorders: Muscular weakness
Injury, Poisoning and Procedural Complications: Fall
Discontinuations Due to Adverse Reactions
In the 7 placebo-controlled studies of adults, 379 (12.9%) galantamine-treated patients (N=2932) and 42 (2.8%) placebo patients (N=1525) discontinued due to an adverse reaction. Those events with an incidence of ≥ 0.5% in the galantamine-treated patients included nausea (225, 7.7%), vomiting (119, 4.1%), decreased appetite (56, 1.9%), dizziness (48, 1.6%), diarrhea (27, 0.9%), headache (26, 0.9%), decreased weight (24, 0.8%), and abdominal pain (15, 0.5%). Those events with an incidence of ≥ 0.5% in placebo patients included nausea (14, 0.9%) and dizziness (8, 0.5%).
In the 5 open-label studies, 103 (7.1%) patients (N=1454) 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%).
The following additional adverse reactions have been identified during post-approval use of RAZADYNE® ER and RAZADYNE® . Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency:
Immune System Disorders: Hypersensitivity
Psychiatric Disorders: Hallucinations
Nervous System Disorders: Seizures
Ear and Labyrinth Disorders: Tinnitus
Vascular Disorders: Hypertension
Hepatobiliary Disorders: Hepatitis, increased hepatic enzyme
Skin and Subcutaneous Tissue Disorders: Stevens-Johnson syndrome, acute generalized exanthematous pustulosis, erythema multiforme