Rivastigmine Transdermal Patch 13.3 mg/24 h: A Review of Its Use in the Management of Mild to Moderate Alzheimer’s Dementia
Rivastigmine is unique among cholinesterase inhibitors commonly used in the treatment of mild to moderate Alzheimer’s disease (AD) in that it is available as a transdermal patch formulation (Exelon® patch, Rivastach® patch, Prometax® patch). The patch is applied once daily and, in the EU (and US), is available in three sizes: 5, 10 and 15 cm2 (releasing 4.6, 9.5 and 13.3 mg rivastigmine/24 h, respectively). In the phase III OPTIMA trial, patients with mild to moderate AD who experienced functional and cognitive decline on the 10 cm2 patch—the recommended maintenance dose—gained additional benefit when their dose was increased to the 15 cm2 patch. For example, 15 cm2 patch recipients showed significantly less functional and cognitive decline than 10 cm2 patch recipients after 24 weeks of double-blind treatment. Patients receiving the 15 cm2 patch also showed significantly less functional, but not cognitive, decline than those receiving the 10 cm2 patch after 48 weeks of double-blind treatment; as such, OPTIMA only met one of its two co-primary endpoints. The 15 cm2 patch was generally well tolerated; although more 15 cm2 than 10 cm2 patch recipients reported adverse events (e.g. nausea and vomiting), fewer 15 cm2 than 10 cm2 patch recipients discontinued treatment due to adverse events. By further slowing functional deterioration without markedly compromising tolerability, increasing the transdermal rivastigmine dose to the 15 cm2 patch has a favourable benefit-risk profile—and therefore represents a valid option—in the treatment of patients with mild to moderate AD who have previously experienced functional and cognitive decline while receiving the 10 cm2 patch.
KeywordsRivastigmine Application Site Reaction Coprimary Endpoint Rivastigmine Patch Exelon
The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made by the authors on the basis of scientific and editorial merit. James Frampton is a salaried employee of Adis/Springer.
- 11.Farlow MR, Somogyi M. Transdermal patches for the treatment of neurologic conditions in elderly patients: a review. Prim Care Companion CNS Disord. 2011;13(6). doi: 10.4088/PCC.11r01149.
- 15.Novartis Europharm Limited. Exelon 4.6 mg/24 h, 9.5 mg/24 h, 13.3 mg/24 h transdermal patch: EU summary of product characteristics. 2013. http://www.medicines.org.uk/emcmobile/medicine/20232/spc. Accessed 13 Jan 2014.
- 16.Novartis Pharmaceuticals Corporation. Exelon® patch (rivastigmine transdermal system): US prescribing information. 2013. http://www.pharma.us.novartis.com/product/pi/pdf/exelonpatch.pdf. Accessed 13 Jan 2014.
- 28.Novartis New Zealand Limited. Exelon®. Rivastigmine 5 cm2, 10 cm2, 15 cm2 and 20 cm2 transdermal patch: New Zealand data sheet. 2013. http://www.medsafe.govt.nz/profs/datasheet/e/Exelonpatch.pdf. Accessed 15 Jan 2014.
- 31.Black S, Bakchine S, Bellelli G, et al. Efficacy of the 13.3 MG/24 h rivastigmine patch on instrumental activities of daily living in the optimising transdermal exelon in mild-to-moderate Alzheimer’s disease (optima) study: prospective subgroup analysis by disease severity and time-to-meet decline (abstract). Alzheimers Dement. 2012;8(4 suppl 1):P603–4.CrossRefGoogle Scholar
- 34.Frolich L, Touchon J, Massaia M, et al. Safety and tolerability of 9.5 mg/24 h (10 cm2) and 13.3 mg/24 h (15 cm2) rivastigmine patches: results from the optimising transdermal exelon in mild-to-moderate Alzheimer’s disease (OPTIMA) study (abstract). Eur J Neurol. 2012;19:467.Google Scholar
- 35.Somogyi M, Grossberg G, Meng X. Influence of Alzheimer’s disease severity on the cognitive efficacy of higher-dose 13.3 mg/24 h rivastigmine patch (abstract no. NR11-32). American Psychiatric Association 166th Annual Meeting; 18–22 May 2013; San Francisco, CA.Google Scholar
- 36.Novartis Europharm Limited. Exelon 13.3 mg/24 h transdermal patch: EU summary of product characteristics. 2008. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000169/WC500032598.pdf. Accessed 22 Jan 2014.
- 37.Alva G, Somogyi M, Meng X, et al. Infrequent skin reactions at the application site of the rivastigmine patch (4.6, 9.5 or 13.3 mg/24 h): analysis of two clinical studies revealed most were tolerable and manageable across all doses [abstract no. P3-299]. 2013 Alzheimer’s Association International Conference; 13–18 July 2013; Boston, MA.Google Scholar
- 38.Cummings J, Frolich L, Black SE, et al. Managing functional and cognitive decline in patients with mild-to-moderate Alzheimer’s disease: a 48-week, randomized, double-blind evaluation of 13.3 mg/24 h (15 cm2) versus 9.5 mg/ 24 h (10 cm2) rivastigmine patch. Neuropsychopharmacol. 2011;36:S223–4.Google Scholar
- 39.Alzheimer’s Association. 2010 Alzheimer’s disease facts and figures. http://www.alz.org/documents_custom/report_alzfactsfigures2010.pdf. Accessed 5 Feb 2014.
- 41.National Institute for Clinical Health and Excellence. Alzheimer’s disease—donepezil, galantamine, rivastigmine and memantine (TA217). 2009. http://publications.nice.org.uk/donepezil-galantamine-rivastigmine-and-memantine-for-the-treatment-of-alzheimers-disease-ta217. Accessed 5 Feb 2014.
- 48.Lee JH, Sevigny J. Effects of body weight on tolerability of rivastigmine transdermal patch: a post hoc analysis of a double-blind trial in patients with Alzheimer disease. Alzheimer Dis Assoc Disord. 2011;25(1):58–62.Google Scholar