D R U G F O C U S Pharmacokinetics of a novel transdermal rivastigmine patch for the treatment of Alzheimer’s disease: a review A. Kurz,1 M. Farlow,2 G. Lefe` vre3 S U M M A R Y Background: Cholinesterase inhibitors have all been available in oral formula- tions, but a rivastigmine transdermal patch has now been developed and is approved in many countries worldwide for the treatment of mild-to-moderate Alzheimer’s disease (AD) (including the USA, Latin America, Europe and Asia). Objectives: To review the available pharmacokinetic data that supported the rationale behind the development of the rivastigmine transdermal patch and its clinical effects in dementia therapy. This article will also discuss how the patch may alter the treatment paradigm for patients with AD. Results: The 9.5 mg ⁄ 24 h rivastigmine patch was shown to provide comparable exposure to the highest recommended doses of capsules (12 mg ⁄ day) with signiﬁcantly lower maximum plasma concentration (Cmax 8.7 vs. 21.6 ng ⁄ ml) and slower absorption rate (tmax 8.1 vs. 1.4 h). In a clinical trial of 1195 AD patients, this translated into similar efﬁcacy with three times fewer reports of nausea and vomiting (7.2% vs. 23.1%, and 6.2% vs. 17.0% respectively). Consequently, more patients in the 9.5 mg ⁄ 24 h patch group achieved their target therapeutic dose at the end of the study, compared with those in the 12 mg ⁄ day capsule group (95.9% vs. 64.4%). Conclusion: The rivastigmine patch provides continuous drug delivery over 24 h and similar efﬁcacy to the highest recommended dose of oral rivastigmine with improved tolerability. This may allow patients to achieve optimal therapeutic doses and to beneﬁt from a longer duration of treatment. Review Criteria The information considered in this review was gathered from key publications comparing efﬁcacy, pharmacokinetic and pharmacodynamic data for the rivastigmine transdermal patch and oral rivastigmine formulations. Clinical data were taken from the pivotal phase-III IDEAL trial. These data were analysed to review the potential beneﬁts of patch therapy vs. oral therapy, and how this may alter the management of dementia patients in clinical practice. Message for the Clinic The rivastigmine transdermal patch provides smooth, continuous delivery of the drug over 24 h. This translates into similar efﬁcacy to the highest recommended dose of oral rivastigmine with an improved tolerability proﬁle. Fewer side effects would allow patients to achieve optimal therapeutic doses. Introduction Cholinesterase inhibitors are widely used in the symptomatic treatment of Alzheimer’s disease (AD) in clinical practice. They act by inhibiting one or both of the enzymes responsible for the hydrolysis of acetylcholine in the synaptic cleft [acetylcholines- terase (AChE) and butyrylcholinesterase (BuChE)], thereby increasing available acetylcholine levels and improving neurotransmission. Three cholinesterase inhibitors are commonly used to treat cognitive symptoms in mild-to-moderate AD: rivastigmine (Exelon ; Novartis, Basel, Switzerland), donepezil (Aricept ; Pﬁzer, New York, NY, USA) and galanta- mine (Reminyl ⁄ Razadyne ; Johnson & Johnson, New Brunswick, NJ, USA). Some cholinesterase inhibitors exhibit a dose– response relationship, with higher drug doses corre- lating with greater enzyme inhibition (1). As AD is a progressive, neurodegenerative disorder where patients deteriorate over time, one goal in clinical practice is to achieve higher doses that maximise the effectiveness of treatment. However, the incidence of adverse events (AEs) associated with oral cholinester- ase inhibitors, particularly nausea and vomiting, also increases with higher doses (2). Consequently, achieving and maintaining high therapeutic doses in clinical practice may be difﬁcult. Rivastigmine is a pseudo-irreversible inhibitor of both AChE and BuChE and has been shown in a number of clinical trials to be efﬁcacious in AD (3–5). Unlike other cholinesterase inhibitors that are only available in oral formulations, a novel transdermal rivastigmine patch has been developed and approved for the treatment of mild-to-moderate AD in many countries worldwide, including the USA, Latin America, Europe and Asia. The pharmacokinetic rationale for the patch suggests that it may provide clinical effectiveness with a more favourable tolerabil- ity proﬁle, allowing a simple one-step titration to the recommended dose. The patch design itself may prove more convenient, easier to use and provide visual ª 2009 The Authors Journal compilation ª 2009 Blackwell Publishing Ltd Int J Clin Pract, May 2009, 63, 5, 799–805 doi: 10.1111/j.1742-1241.2009.02052.x 1Department of Psychiatry and Psychotherapy, Technische Universita¨ t Mu¨ nchen, Munich, Germany 2Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, USA 3Novartis, Translational Sciences, Basel, Switzerland Correspondence to: Professor Alexander Kurz, Department of Psychiatry and Psychotherapy, Technische Universita¨ t Mu¨ nchen, Munich, Germany Tel.: + 49 89 4140 4285 Fax: + 49 89 4140 4923 Email: alexander.kurz@lrz.tu- muenchen.de Disclosures Alexander Kurz has received speaker honoraria and advisory board consultancy fees from Novartis; Martin Farlow receives grant support, speaker honoraria and consultancy fees from Novartis; Gilbert Lefe` vre is an employee of Novartis. 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