Following a lack/loss of efficacy or safety/tolerability problems with an initial pharmacological treatment, switching to another medication within the same drug class is a common therapeutic strategy employed across many clinical areas. For the treatment of AD with cholinesterase (ChE) inhibitors, this an increasingly important concept, supported by clinical data and experience. Continuing with another ChE inhibitor after failure with an initial agent provides patients with another chance to benefit from treatment.
Rivastigmine is a dual inhibitor of acetyl- and butyrylcholinesterase (AChE and BuChE). Recently, studies have examined the clinical benefits of switching to rivastigmine in AD patients who failed to benefit from previous donepezil treatment. For example, a 26-week open-label study in 382 patients showed that switching to rivastigmine, following a lack/loss of efficacy with donepezil led to clinical benefits improvement/stabilisation in global function) in 56.2% of patients. Rivastigmine was well tolerated following the switch. Poor tolerability with donepezil was not predictive of similar problems with rivastigmine treatment.
In the summer of 2002, leading neurologists and psychiatrists attended a medical experts’ meeting to discuss current ChE inhibitor switching data and guidelines. The panel also aimed to reach consensus on "whom to switch", "when to switch" and "how to switch." They concluded the following:
Whom to switch: Switching should not be considered in patients responding to current treatment (improvement or stabilisation in symptoms) and who have no tolerability/safety problems.
When to switch: Physicians should monitor and assess patients on an individual basis, taking into consideration feedback from the caregiver, where appropriate. Patients showing lack/loss of efficacy should have been receiving treatment for at least 6 months before switching, allowing sufficient time to reach optimal dose and assessment of clinical progression.
How to switch: In patients experiencing no safety/tolerability problems with an initial agent, a switch with no washout period can be considered. In contrast, patients who experience safety/tolerability problems should undergo a washout period for approximately 7 days or until the symptoms resolve. The second agent should be initiated at the recommended starting dose and generally increased according to prescribing information (preferably increasing the dose after a minimum of 4 weeks).
In conclusion, there is growing evidence that switching ChE inhibitors is an important therapeutic strategy in the management of AD, enabling patients to benefit from maximum long-term benefits. To date, most supportive data are derived from studies where patients have been switched from donepezil to rivastigmine.
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