Pharmacokinetics of the rivastigmine patch 805 to result in the development of erythema. Daily rota- tion of the application site is recommended in the product label to minimise skin irritation, avoiding the exact same spot for at least 14 days (although consecutive patches may be applied to the same ana- tomical site). Conclusion Overall, current clinical data support the pharmaco- kinetic rationale of the rivastigmine patch, demon- strating that the smooth continuous drug delivery provided by transdermal administration translates into comparable efﬁcacy with an improved tolerabil- ity proﬁle vs. oral administration. This drug adminis- tration route could therefore allow optimal therapeutic dosing, potentially further improving the effectiveness of treatment. The rivastigmine patch may be the optimal way to deliver rivastigmine to treat AD, and may be the ﬁrst of several transdermal options in the ‘next generation’ of cholinesterase inhibitor formulations. Acknowledgements This review was sponsored by Novartis Pharma AG, Basel, Switzerland. Alpha-Plus Medical Communica- tions Ltd (UK) provided editorial support with the production of the manuscript. Author contributions All authors were involved in the interpretation, draft- ing, critical revision and approval of this article. References 1 Cutler NR, Polinsky RJ, Sramek JJ et al. Dose-dependent CSF ace- tylcholinesterase inhibition by SDZ ENA 713 in Alzheimer’s dis- ease. Acta Neurol Scand 1998; 97: 244–50. 2 Imbimbo BP. Pharmacodynamic-tolerability relationships of cho- linesterase inhibitors for Alzheimer’s disease. CNS Drugs 2001; 15: 375–90. 3 Corey-Bloom J, Anand R, Veach J. A randomized trial evaluating the efﬁcacy and safety of ENA 713 (rivastigmine tartrate), a new acetylcholinesterase inhibitor, in patients with mild to moderately severe Alzheimer’s disease. Int J Geriatr Psychopharmacol 1998; 1: 55–65. 4 Ro¨sler M, Anand R, Cicin-Sain A et al. Efﬁcacy and safety of riv- astigmine in patients with Alzheimer’s disease: international rando- mised controlled trial. BMJ 1999; 318: 633–8. 5 Schneider LS, Anand R, Farlow MR. Systematic review of the efﬁ- cacy of rivastigmine for patients with Alzheimer’s disease. Int J Geriatr Psychopharmacol 1998; 1 (Suppl. 1): S26–34. 6 Cummings J, Lefe`vre G, Small G, Appel-Dingemanse S. Pharmaco- kinetic rationale for the rivastigmine patch. Neurology 2007; 69 (4 Suppl. 1): S10–3. 7 Blesa R, Ballard C, Orgogozo J-M, Lane R, Thomas S. Caregiver preference for rivastigmine patches versus capsules for the treat- ment of Alzheimer disease. Neurology 2007; 69 (Suppl. 1): S23–8. 8 WIPO (WO ⁄ 2008 ⁄ 021113). Transdermal methods and systems for treating Alzheimer’s disease. http://www.wipo.int/pctdb/en/wo. jsp?WO=2008021113 (accessed March 2009). 9 Feldman HH, Lane R. Rivastigmine: a placebo-controlled trial of BID and TID regimens in patients with Alzheimer’s disease. J Neu- rol Neurosurg Psychiatry 2007; 78: 1056–63. 10 Zhao Q, Jannssens L, Verhaeghe T, Brashear HR, Truyen L. Phar- macokinetics of extended-release and immediate-release formula- tions of galantamine at steady state in healthy volunteers. Curr Med Res Opin 2005; 21: 1547–54. 11 Nitti VW, Sanders S, Staskin DR et al. Transdermal delivery of drugs for urologic applications: basic principles and applications. Urology 2006; 67: 657–64. 12 Bos JD, Meinardi MM. The 500 Dalton rule for the skin penetra- tion of chemical compounds and drugs. Exp Dermatol 2000; 9: 165–9. 13 Lefe`vre G, Se˛dek G, Jhee S et al. Pharmacokinetics and pharmaco- dynamics of the novel daily rivastigmine transdermal patch com- pared with twice-daily capsules in Alzheimer’s disease patients. Clin Pharmacol Ther 2008; 83: 106–14. 14 Smith BP, Vandenhende FR, DeSante KA et al. Conﬁdence interval criteria for assessment of dose proportionality. Pharm Res 2000; 17: 1278–83. 15 Mercier F, Lefe`vre G, Huang HL, Schmidli H, Amzal B, Dinge- manse SA. Rivastigmine exposure provided by a transdermal patch versus capsules. Curr Med Res Opin 2007; 23: 3199–204. 16 Lefe`vre G, Pommier F, Se˛dek G et al. Pharmacokinetics and bio- availability of the novel rivastigmine transdermal patch versus riv- astigmine oral solution in healthy elderly subjects. J Clin Pharmacol 2008; 48: 246–52. 17 Lefe`vre G, Se˛dek G, Huang HL et al. Pharmacokinetics of a riv- astigmine transdermal patch formulation in healthy volunteers: relative effects of body site application. J Clin Pharmacol 2007; 47: 471–8. 18 Spencer CM, Noble S. Rivastigmine. A review of its use in Alzhei- mer’s disease. Drugs Aging 1998; 13: 391–411. 19 Winblad B, Cummings J, Andreasen N et al. A six-month double- blind, randomized, placebo-controlled study of a transdermal patch in Alzheimer’s disease – rivastigmine patch versus capsule. Int J Geriatr Psychiatry 2007; 22: 456–67. 20 Winblad B, Machado JC. Use of rivastigmine transdermal patch in the treatment of Alzheimer’s disease. Expert Opin Drug Deliv 2008; 5: 1377–86. Paper received November 2008, accepted February 2009 ª 2009 The Authors Journal compilation ª 2009 Blackwell Publishing Ltd Int J Clin Pract, May 2009, 63, 5, 799–805