Emerald B. Foster, PharmD

Alzheimer’s disease (AD) is a progressive, neurodegenerative disorder of unknown etiology associated with a loss of acetylcholine. The loss of acetylcholine disrupts cortical functions such as memory, thinking, and orientation, resulting in a decline in cognition, behavior, and daily functioning.

 Treatment options include acetylcholinesterase inhibitors (AChEIs), which exhibit clinical benefits through the inhibition of the cholinesterase enzyme. Inhibition of the cholinesterase enzyme enhances cholinergic function, eventually improving, stabilizing, or slowing disease 

 Alzheimer’s disease progresses slowly,

taking between 3 and 18 years to advance from the earliest

symptoms to death, with an average duration of 8 years.

AChEIs available in the United States include donepezil,

galantamine immediate-release (IR) and extended-release

(ER), rivastigmine (oral capsule and patch), and tacrine. In

2000, donepezil was the most commonly prescribed AChEI

in the United States and accounted for approximately 50%

of all prescriptions for the treatment of AD; rivastigmine was

the second most commonly prescribed medication, accounting

for about 6% of all prescriptions for AD.

rarely used in the United States because of the increased risk

by the US Food and Drug Administration for AD was galantamine

in 2001, which is now available as an ER capsule for

Unlike other AChEIs that target only the acetylcholinesterase receptors, galantamine competitively and reversibly inhibits the acetylcholinesterase enzyme and modulates the nicotinic acetylcholine receptors. Modulation of nicotinic receptors allows for a stronger response at deteriorating cholinergic neurons. This unique mechanism of action may provide a potential advantage over other AChEIs in patients with AD.

 As a class, AChEIs have shown superior efficacy compared with placebo for the symptomatic treatment of mild to moderate AD and have been shown to delay the progression of AD by at least 6 months.

 Moreover, patients who do not respond to one AChEI may benefit with adifferent AChEI.

There are 5 key reasons for switching therapies in patients with AD: (1) inefficacy or perceived inefficacy, (2) poor tolerability, (3) physician preference, (4) patient or caregiver request, and (5) economic considerations.

 Efficacy, safety, and tolerability must be considered when switching patients from one AChEI to another, as well as the optimal washout period for the discontinued medication and the optimal dose-escalation period for the replacement medication. Preliminary data from a trial published by Rasmusen et al showed that patients can tolerate a therapeutic interchange from one AChEI to another using a zero-day washout period.

 The most common side effects experienced were gastrointestinal (GI), including nausea (17.2%) and diarrhea (12.1%), both of which were tolerated and commonly seen with AChEIs.

 No other clinically significant side effects were observed.

Using a zero-day washout period was necessary to maintain enough inhibition of the acetylcholinesterase enzyme to prevent destabilization. A study evaluating a switch from donepezil to galantamine IR using washout periods of 4 and 7 days reported an increase in adverse effects with increasing washout periods.

 Moreover, there were more discontinuations in the 7-day washout period compared with the 4-day washout period (10.6% and 4%, respectively).

Ferris et al reported that prior exposure to an AChEI was not predictive of galantamine response, essentially concluding that patients with and without prior AChEI therapy had similar efficacy outcomes and tolerated galantamine well.

 To further strengthen the argument for galantamine’s use in AD, Wilcock et al provided evidence that patients on galantamine would experience improved clinical outcomes compared with patients on donepezil.

 Mini-Mental State Exam (MMSE) scores of patients receiving galantamine at 52 weeks did not differ significantly from baseline, whereas MMSE scores of patients on donepezil deteriorated.

 Furthermore, caregivers of patients receiving galantamine also reported decreased burden compared with donepezil, creating a case from the caregiver perspective.

Therapeutic interchanges with other medications have proved to be efficacious, safe, and cost saving.

 Switching from a brand to generic product has demonstrated economic benefits while maintaining clinical efficacy and safety.

 However, for some medications with narrow therapeutic ranges, therapeutic interchange from brand to generic may lead to destabilization

 Although there is a potential for cost savings with therapeutic interchanges, establishing clinical efficacy and safety should take priority over economic benefits.

Generic galantamine ER may potentially reduce some of the economic burden on the healthcare system. Therapeutic interchange from donepezil to galantamine ER may be cost saving while maintaining clinical stability. In addition, galantamine ER is dosed once a day, much like donepezil, which makes the therapeutic interchange convenient for patients and caregivers. This has the potential to reduce medication errors resulting from patients having to take galantamine IR, which is dosed twice a day. Moreover, in a disease state such as AD, it is important to reduce the frequency of doses in order to enhance patient and caregiver administration adherence.

In 2008, the Veterans Affairs San Diego Healthcare System (VASDHS) developed a strategy to perform a therapeutic interchange from donepezil to galantamine ER upon refill because of generic galantamine ER availability and potential for cost savings. The therapeutic interchange was approved by the pharmacy and therapeutics committee, the Veterans Integrated Service Network 22 Pharmacy Benefits Management group, and local geriatric-psychiatry and neurology experts. The purpose of this study was to evaluate the safety and tolerability of therapeutic interchange from donepezil to galantamine ER at our facility and to determine the number of patients who switched back to donepezil. To date, there is a gap in the literature evaluating the clinical efficacy and safety of switching AD patients from donepezil to galantamine ER in a Veterans Affairs setting.

This study was conducted at the VASDHS, a 238-bed medical center with specialized clinics servicing the veteran population in areas such as cardiology, endocrinology,gastroenterology, hemodialysis, infectious disease, neurology,ophthalmology, psychiatry, and rheumatology. TheVASDHS uses the Computerized Patient Records Systemto document notes, write prescriptions, order laboratorytests, view images, and perform medication reconciliation.

Patients with active prescriptions for donepezil underwent a therapeutic interchange to galantamine ER between April 2008 and July 2008, after which patients were followed for an additional 3 months to evaluate tolerability and safety (

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