Side Effects of Razadyne ER (galantamine)

Razadyne ER (galantamine) is a cholinesterase inhibitor used to treat patients with Alzheimer's disease, a form of dementia. Cholinesterase inhibitors inhibit (block) the action of acetylcholinesterase, the enzyme responsible for the destruction of acetylcholine. Acetylcholine is one of several neurotransmitters in the brain, chemicals that nerve cells use to communicate with one another.

Reduced levels of acetylcholine in the brain are believed to be responsible for some of the symptoms of Alzheimer's disease. By blocking the enzyme that destroys acetylcholine, Razadyne ER increases the concentration of acetylcholine in the brain, and this increase is believed to be responsible for the improvement in thinking. 

Common side effects of Razadyne ER are usually mild and temporary and include

• nausea,
• vomiting,
• diarrhea, and
• weight loss.

These side effects generally occur during the beginning of treatment or when the dose is increased. 

Other important side effects of Razadyne ER include

• headache,
• abdominal pain,
• fatigue,
• slow heart rate,
• depression,
• sleepiness, and
• fainting.

Drug interactions of Razadyne ER include drugs with anticholinergic properties and which cross into the brain, such as atropine, benztropine and trihexyphenidyl, which produce opposite effects to (counteract) Razadyne ER.

Drugs such as ketoconazole and paroxetine that reduce the activity of liver enzymes that break down Razadyne ER may increase blood levels of and, therefore, the side effects of Razadyne ER.

Razadyne ER may add to the neuromuscular blocking effect of succinylcholine and similar drugs that are used during surgical anesthesia.

Unlike donepezil, Razadyne ER does not increase blood levels of other medications and increase their risk for side effects.

No studies have been performed with use of Razadyne ER in pregnant women. Physicians must weigh the potential benefits against the potential risks of Razadyne ER before prescribing it for pregnant women.

It is unknown if Razadyne ER is secreted in breast milk. Consult your doctor before breastfeeding.

The most frequent side effects seen with galantamine are:

• nausea,
• vomiting,
• diarrhea, and
• anorexia (weight loss).

These side effects generally occur during the beginning of treatment or when the dose is increased. These side effects typically are mild and temporary. Taking galantamine with food and ensuring adequate fluid intake may reduce the impact of these side effects.

Other important side effects include:

• headache,
• abdominal pain,
• fatigue,
• slow heart rate,
• depression,
• sleepiness, and
• fainting.

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 subjects with mild cognitive impairment (MCI)

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

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%).

Postmarketing Experience

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
• 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

Use With Anticholinergics

• Galantamine has the potential to interfere with the activity of anticholinergic medications.

Use With Cholinomimetics And Other Cholinesterase Inhibitors

• A synergistic effect is expected when cholinesterase inhibitors are given concurrently with succinylcholine, other cholinesterase inhibitors, similar neuromuscular blocking agents or cholinergic agonists such as bethanechol.