Objective: Assessment of tolerability in mild to moderately severe AD patients immediately switched to rivastigmine after poor response to donepezil.
Design: The only currently approved treatments for Alzheimer’s disease utilize cholinesterase inhibitors (ChEI) to ameliorate the cholinergic deficit and enhance remaining cholinergic function. Three ChEIs are widely prescribed: donepezil and galantamine are specific acetylcholinesterase (AChE) inhibitors while rivastigmine is a dual inhibitor possessing the ability to inhibit both of the enzymes involved in ACh hydrolysis; AChE and butyrylcholinesterase. While all ChEIs increase brain levels of acetylcholine (ACh), the agents differ markedly in pharmacologic, pharmacokinetic, and pharmacodynamic profiles. Due to these differences, switching patients from one ChEI to another may provide valuable clinical benefits for AD patients who are experiencing declining efficacy or fail to respond to a current cholinergic therapy. As in many other therapeutic areas, switching between agents within a given drug class should be considered before withdrawal of treatment.
Materials and Methods: This is an interim analysis from an ongoing open-label, multi-center, study to assess the tolerability of an immediate switch from donepezil (10 mg/d) to rivastigmine (1.5 mg.bid). Fifty-one outpatients (23 male, 28 female) with mild to moderately severe AD (baseline MMSE score 8-25) responding poorly following at least six months treatment with donepezil were enrolled. Patients entering the study had at least a two-point decline in MMSE score during treatment with donepezil. The average rate of decline during 6-12 months of donepezil treatment prior to entering the study was -4.6 MMSE points. Rivastigmine treatment was initiated at 1.5 mg bid within 24 to 36 hours after the last dose of donepezil. Patients were scheduled to remain at the 1.5 mg bid rivastigmine dose for 28 days.
Results: 47 patients completed 28 days of treatment. Switching cholinesterase therapy was well tolerated. Only two patients (3.9%) in the study experienced nausea and one (2.0%) experienced vomiting. The overall incidence of gastrointestinal AEs was 7.8%. 41% of patients experienced at least one adverse event and 4 patients (7.8%) discontinued due to adverse events, including: irritability, confusion, vomiting and worsening social withdrawal with echolalia.
Conclusion: The results from this interim analysis indicate that in patients responding poorly to donepezil, an immediate switch to rivastigmine is well tolerated.
Back to PB Tuesday Poster Sessions
Back to The Eleventh International Congress