Galantamine (Page 2 of 6)

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 subjects with mild cognitive impairment (MCI) [see Warnings and Precautions (5.8)]

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 in galantamine-treated patients from double-blind clinical trials (≥ 5%) 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 3956 galantamine-treated patients who participated in 8 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 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	Galantamine (n = 3956) %	Placebo (n = 2546) %
Metabolism and Nutrition Disorders
Decreased appetite	7.4	2.1
Psychiatric Disorders
Depression	3.6	2.3
Nervous System Disorders
Dizziness	7.5	3.4
Headache	7.1	5.5
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 pain	3.8	2.0
Abdominal discomfort	2.1	0.7
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 5-7 days.

Other Adverse Reactions Observed in Clinical Trials of Galantamine

The following adverse reactions occurred in <1% of all galantamine-treated patients (N=3956) 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

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=3956) and 56 (2.2%) placebo patients (N=2546) 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=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%).