Acetylcholinesterase inhibitors for treating dementia symptoms - a safety evaluation

ABSTRACT

Introduction: The prevalence of Alzheimer’s disease (AD) continues to rise, while treatment options for cognitive impairment are limited. Acetylcholinesterase inhibitors (AChEIs) aim to provide symptomatic benefit for cognitive decline, however these drugs are not without adverse events (AEs). The safety profile of each drug must be taken carefully into consideration before being prescribed, as new dosages and formulations have recently been approved.

Areas covered: Donepezil, galantamine and rivastigmine are the three AChEIs approved for the treatment of varying stages of AD. Numerous clinical trials and post-marketing studies have evaluated the safety of these medications. This article will review the safety, efficacy and tolerability of these drugs in treating AD. Topics including pharmacovigilance databases, concomitant drug interactions, prescribing cascades, and treatment discontinuation are also covered.

Expert opinion: AChEI use in those with mild, moderate or severe AD provide modest improvements in cognition, function and behavior. The pharmacological treatment of AD using AChEIs is associated with generally mild AEs. Differences in drug formulations should be taken into account when determining the most appropriate route of administration for each individual. Furthermore, discontinuation of AChEIs must be carefully monitored as it may be associated with worsening cognitive impairment.

KEYWORDS:

• Alzheimer’s disease
• adverse events
• acetylcholinesterase inhibitors
• donepezil
• galantamine
• pharmacovigilance
• rivastigmine
• safety

Article highlights

• Acetylcholinesterase inhibitors (AChEIs) are used to slow the progression of cognitive decline in AD and have shown modest improvements in scores on tests of cognitive function such as the MMSE and SIB.

• The most common AEs associated with AChEIs are GI related and include nausea, vomiting and diarrhea; however there are also concerns of cardiovascular AEs such as bradycardia.

• Donepezil is available in a higher sustained release 23mg/day dose compared to the 5mg/day or 10mg/day dose to provide additional benefits to those with severe AD.

• Transdermal administration of rivastigmine may be more tolerable for some individuals and may reduce cholinergic GI AEs.

• Once daily ER galantamine may improve patient adherence compared to the twice daily IR form.

• Pharmacovigilance studies confirm the mild and transient nature of AEs related to AChEIs that are evident in clinical trials. Interactions with concomitantly prescribed bradycardiac drugs may increase the likelihood of cardiovascular AEs. Clinicians should be vigilant of prescribing cascades that have been described with this class of drugs.

This box summarizes key points contained in the article.

Declaration of interest

N Herrman is supported by research grants from Lundbeck Canada Inc, Axovant Sciences Inc and has receieved consultation fees from Merck & Co Inc., Eli Lilly & Co., Astellas Scientifc and Medical Affairs Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper has not been funded.