Advertisement

Drugs & Aging

, Volume 31, Issue 8, pp 639–649 | Cite as

Rivastigmine Transdermal Patch 13.3 mg/24 h: A Review of Its Use in the Management of Mild to Moderate Alzheimer’s Dementia

  • James E. FramptonEmail author
Adis Drug Evaluation

Abstract

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.

Keywords

Rivastigmine Application Site Reaction Coprimary Endpoint Rivastigmine Patch Exelon 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Disclosure

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.

References

  1. 1.
    Jalbert JJ, Daiello LA, Lapane KL. Dementia of the Alzheimer type. Epidemiol Rev. 2008;30:15–34.PubMedCrossRefGoogle Scholar
  2. 2.
    Lobo A, Launer LJ, Fratiglioni L, et al. Prevalence of dementia and major subtypes in Europe: a collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group. Neurology. 2000;54(11 suppl 5):S4–9.PubMedGoogle Scholar
  3. 3.
    Anderson CK, Lauridsen J, Andersen K, et al. Cost of dementia: impact of disease progression estimated in longitudinal data. Scand J Public Health. 2003;31(2):119–25.CrossRefGoogle Scholar
  4. 4.
    Ubhi K, Masliah E. Alzheimer’s disease: recent advances and future perspectives. J Alzheimers Dis. 2013;33(Suppl 1):S185–94.PubMedGoogle Scholar
  5. 5.
    Terry AV Jr, Buccafusco JJ. The cholinergic hypothesis of age and Alzheimer’s disease-related cognitive deficits: recent challenges and their implications for novel drug development. J Pharmacol Exp Ther. 2003;306:821–7.PubMedCrossRefGoogle Scholar
  6. 6.
    Holzer S, Warner JP, Iliffe S. Diagnosis and management of the patient with suspected dementia in primary care. Drugs Aging. 2013;30:667–76.PubMedCrossRefGoogle Scholar
  7. 7.
    Dhillon S. Rivastigmine transdermal patch: a review of its use in the management of dementia of the Alzheimer’s type. Drugs. 2011;71(9):1209–31.PubMedCrossRefGoogle Scholar
  8. 8.
    Hort J, O’Brien JT, Gainotti G, et al. EFNS guidelines for the diagnosis and management of Alzheimer’s disease. Eur J Neurol. 2010;17(10):1236–48.PubMedCrossRefGoogle Scholar
  9. 9.
    Spencer CM, Noble S. Rivastigmine: a review of its use in Alzheimer’s disease. Drugs Aging. 1998;13(5):391–411.PubMedCrossRefGoogle Scholar
  10. 10.
    Yang LPH, Keating GM. Rivastigmine transdermal patch: in the treatment of dementia of the Alzheimer’s type. CNS Drugs. 2007;21(11):957–65.PubMedCrossRefGoogle Scholar
  11. 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.
  12. 12.
    Guay DR. Rivastigmine transdermal patch: role in the management of Alzheimer’s disease. Consult Pharm. 2008;23(8):598–609.PubMedCrossRefGoogle Scholar
  13. 13.
    Lefevre G, Sedek G, Jhee SS, et al. Pharmacokinetics and pharmacodynamics of the novel daily rivastigmine transdermal patch compared with twice-daily capsules in Alzheimer’s disease patients. Clin Pharm Ther. 2008;83(1):106–14.CrossRefGoogle Scholar
  14. 14.
    Oertel W, Ross JS, Eggert K, et al. Rationale for transdermal drug administration in Alzheimer disease. Neurology. 2007;69(4 Suppl 1):S4–9.PubMedCrossRefGoogle Scholar
  15. 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. 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.
  17. 17.
    Darvesh S, Walsh R, Kumar R, et al. Inhibition of human cholinesterases by drugs used to treat Alzheimer disease. Alzheimer Dis Assoc Disord. 2003;17(2):117–26.PubMedCrossRefGoogle Scholar
  18. 18.
    Rakonczay Z. Potencies and selectivities of inhibitors of acetylcholinesterase and its molecular forms in normal and Alzheimer’s disease brain. Acta Biol Hung. 2003;54(2):183–9.PubMedCrossRefGoogle Scholar
  19. 19.
    Greig NH, Utsuki T, Yu Q, et al. A new therapeutic target in Alzheimer’s disease treatment: attention to butyrylcholinesterase. Curr Med Res Opin. 2001;17(3):159–65.PubMedCrossRefGoogle Scholar
  20. 20.
    Weinstock M, et al. Selectivity of cholinesterase inhibition: clinical implications for the treatment of Alzheimer’s disease. CNS Drugs. 1999;12(4):307–23.CrossRefGoogle Scholar
  21. 21.
    Eskander MF, Nagykery NG, Leung EY, et al. Rivastigmine is a potent inhibitor of acetyl- and butyrylcholinesterase in Alzheimer’s plaques and tangles. Brain Res. 2005;1060(1–2):144–52.PubMedCrossRefGoogle Scholar
  22. 22.
    Jann MW. Rivastigmine, a new-generation cholinesterase inhibitor for the treatment of Alzheimer’s disease. Pharmacotherapy. 2000;20(1):1–12.PubMedCrossRefGoogle Scholar
  23. 23.
    Muhlack S, Przuntek H, Müller T. Transdermal rivastigmine treatment does not worsen impaired performance of complex motions in patients with Alzheimer’s disease. Pharmacopsychiatry. 2006;39(1):16–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Grossberg GT, Sadowsky C, Olin JT. Rivastigmine transdermal system for the treatment of mild to moderate Alzheimer’s disease. Int J Clin Pract. 2010;64(5):651–60.PubMedCrossRefGoogle Scholar
  25. 25.
    Lee N-Y, Kang Y-S. The inhibitory effect of rivastigmine and galantamine on choline transport in brain capillary endothelial cells. Biomol Ther. 2010;18(1):65–70.CrossRefGoogle Scholar
  26. 26.
    Lefevre G, Buche M, Sedek G, et al. Similar rivastigmine pharmacokinetics and pharmacodynamics in Japanese and white healthy participants following the application of novel rivastigmine patch. J Clin Pharmacol. 2009;49(4):430–43.PubMedCrossRefGoogle Scholar
  27. 27.
    Lefevre G, Sedek G, Huang HL, et al. Pharmacokinetics of a rivastigmine transdermal patch formulation in healthy volunteers: relative effects of body site application. J Clin Pharmacol. 2007;47(4):471–8.PubMedCrossRefGoogle Scholar
  28. 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.
  29. 29.
    Cummings J, Froelich L, Black SE, et al. Randomized, double-blind, parallel-group, 48-week study for efficacy and safety of a higher-dose rivastigmine patch (15 vs. 10 cm2) in Alzheimer’s disease. Dement Geriatr Cogn Disord. 2012;33(5):341–53.PubMedCrossRefGoogle Scholar
  30. 30.
    Grossberg G, Cummings J, Frolich L, et al. Efficacy of higher dose 13.3 mg/24 h rivastigmine patch on instrumental activities of daily living in patients with mild-to-moderate Alzheimer’s disease. Am J Alzheimers Dis Other Demen. 2013;28(6):583–91.PubMedCrossRefGoogle Scholar
  31. 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
  32. 32.
    Molinuevo JL, Grossberg G, Frolich L, et al. Predictors of response to the 13.3 and 9.5 mg/24 h rivastigmine patch: the optimizing transdermal exelon in mild-to-moderate Alzheimer’s disease (optima) study (abstract). J Neurol Sci. 2013;333:e336.CrossRefGoogle Scholar
  33. 33.
    Molinuevo JL, Cummings J, Frolich L, et al. High-dose 13.3 mg/24 h rivastigmine patch efficacy and safety in mild-to-moderate Alzheimer’s disease with and without concomitant memantine use (abstract). J Neurol Sci. 2013;333:e348.CrossRefGoogle Scholar
  34. 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. 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. 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. 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. 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. 39.
    Alzheimer’s Association. 2010 Alzheimer’s disease facts and figures. http://www.alz.org/documents_custom/report_alzfactsfigures2010.pdf. Accessed 5 Feb 2014.
  40. 40.
    Qaseem A, Snow V, Cross JTJ, et al. Current pharmacologic treatment of dementia: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. 2008;148(5):370–8.PubMedCrossRefGoogle Scholar
  41. 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.
  42. 42.
    Bullock R, Touchon J, Bergman H, et al. Rivastigmine and donepezil treatment in moderate to moderately-severe Alzheimer’s disease over a 2-year period. Curr Med Res Opin. 2005;21(8):1317–27.PubMedCrossRefGoogle Scholar
  43. 43.
    Blesa R, Ballard C, Orgogozo JM, et al. Caregiver preference for rivastigmine patches versus capsules for the treatment of Alzheimer disease. Neurology. 2007;69(4 Suppl 1):S23–8.PubMedCrossRefGoogle Scholar
  44. 44.
    Winblad B, Kawata AK, Beusterien KM, et al. Caregiver preference for rivastigmine patch relative to capsules for treatment of probable Alzheimer’s disease. Int J Geriatr Psychiatry. 2007;22(5):485–91.PubMedCrossRefGoogle Scholar
  45. 45.
    Riedel O, Emmrich A, Klotsche J, et al. Alzheimer’s disease: differences of transdermal versus oral treatment on caregiving time. Dement Geriatr Cogn Disord Extra. 2012;2:468–80.CrossRefGoogle Scholar
  46. 46.
    Reñé R, Ricart J, Hernandez B, et al. From high doses of oral rivastigmine to transdermal rivastigmine patches: user experience and satisfaction among caregivers of patients with mild to moderate Alzheimer disease. Neurologia. 2014;29(2):86–93.PubMedCrossRefGoogle Scholar
  47. 47.
    Inglis F. The tolerability and safety of cholinesterase inhibitors in the treatment of dementia. Int J Clin Pract Suppl. 2002;127:45–63.PubMedGoogle Scholar
  48. 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
  49. 49.
    Greenspoon J, Herrmann N, Adam DN. Transdermal rivastigmine: management of cutaneous adverse events and review of the literature. CNS Drugs. 2011;25(7):575–83.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  1. 1.AdisAucklandNew Zealand

Personalised recommendations