Rivastigmine | ALZFORUM (2024)

Rivastigmine

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Name: Rivastigmine
Synonyms: Exelon™, Rivastigmine tartrate , Rivastach® Patch, Prometax®, SDZ ENA 713
Chemical Name: (S)-3-[1-(dimethylamino)ethyl]phenyl N-ethyl-N-methylcarbamate
Therapy Type: Small Molecule (timeline)
Target Type: Cholinergic System (timeline)
Condition(s): Alzheimer's Disease, Parkinson's Disease Dementia
U.S. FDA Status: Alzheimer's Disease (Approved), Parkinson's Disease Dementia (Approved)
Company: Novartis Pharmaceuticals Corporation
Approved for: Mild to moderate Alzheimer’s disease and mild to moderate dementia related to Parkinson's disease

Rivastigmine is a reversible inhibitor of both the acetylcholinesterase and butyrylcholinesterase enzymes. It is widely used for the treatment of Alzheimer's across its mild, moderate, and severe stages, as well as for the treatment of dementia associated with Parkinson's disease (PDD). Rivastigmine was first approved to be marketed for AD in 1997 in Switzerland, and in the years since has come to be available in some 80 countries worldwide, including the United States, Canada, and Europe, for both AD and PDD.

This drug was originally formulated as a twice-daily oral capsule. It was the first AD therapy to be made available as a skin patch that continuously delivers the drug over 24 hours. The patch is sold in three doses. By way of transdermal absorption, the patch provides steady plasma concentrations of rivastigmine and bypasses first-pass metabolism in the intestine and liver. Because it generates fewer gastrointestinal side effects, it enables patients to receive a higher therapeutic dose (Cummings et al., 2007). Generic versions of different doses of rivastigmine capsules started becoming available in 2010; a generic patch came out in 2015.

Rivastigmine's side effects are consistent with class effects of cholinesterase inhibition. They include most commonly nausea, vomiting, diarrhea, and loss of appetite; less frequently, agitation, depression, dizziness, fatigue/sleeplessness, and others. Side effects tend to be strongest in the beginning weeks, when the dose is titrated up to the therapeutic level, and milder in the maintenance phase. Apart from rare skin sensitivity reactions, the patch is generally better tolerated than the capsules.

About 75 clinical trials Phase 2 and higher have been registered with rivastigmine. For example, in a six-month North American trial comparing a dose of 6-12 mg/day to 1-4 mg/day and to placebo in 699 patients with mild to moderate AD, rivastigmine capsules showed a modest but dose-dependent benefit on cognition, function, and activities of daily living as measured by the ADAS-cog, the CIBIC-plus, and the Progressive Deterioration Scale (PDS), respectively. Similar results were shown in a European trialin 725 patients with mild to moderate AD that compared 6-12mg/day to 1-4mg/day of rivastigmine and placebo, also for six months and using the same outcome measures. Only a quarter to a third of patients had a significant treatment response to rivastigmine capsules (Corey-Bloom et al., 1998; Rösler et al., 1999).

The skin patch formulation was evaluated in the six-month, Phase 3 IDEAL (Investigation of transDermal Exelon in ALzheimer's disease) study in 1,195 patients with mild to moderate AD. Participants received either one of two doses of the rivastigmine patch (9.5 or 17.4 mg over the course of 24 hours), 6 mg twice-daily capsules, or placebo. On efficacy, both patch doses outperformed placebo; the lower-dose patch with a similar effect to that of the capsules, the high-dose patch adding a small benefit on cognition. With the patch, the incidence of gastrointestinal complaints dropped nearly to that of placebo, and two-thirds of caregivers said they preferred the patch. A six-month, 716-patient trial comparing a 4.6 mg/24-hour to a 13.3 mg/24-hour patch reported that the higher dose was more efficacious at comparable tolerability (e.g.,Winblad et al., 2007;Grossberg et al., 2011;Farlow et al., 2013). An open-label study in a real-life clinical setting outside of randomized controlled trials reported that 969 patients with mild to moderate AD treated with the rivastigmine patch tended to maintain cognitive and global function over 18 months (Gauthier et al., 2013).

Most double-blind RCTs of rivastigmine lasted three to six months. Some longer-term treatment data are available from open-label extensions or from analyses of clinical observation. For example, one study of 1,998 patients treated for up to five years found that their mean baseline MMSE score of 19.3 declined to above 10 points after five years of rivastigmine treatment, while model-based projections predicted that without treatment it would have declined to below 10 points by three years. Other studies reported clinically meaningful treatment benefits compared with historical controls for two years of treatment (Small et al., 2005;Grossberg et al., 2004).

Overall, the acetylcholinesterase therapies donepezil, rivastigmine, and galantamine are viewed as having similar efficacy and safety, though few side-by-side comparisons exist. One three-month study randomized 111 patients with mild to moderate AD to either donepezil titrated up to 10 mg once daily, or rivastigmine capsules up to 6 mg twice daily. Both regimens led to comparable symptomatic benefits on cognition. Donepezil was better tolerated, though this has since changed with the rivastigmine patch (Wilkinson et al., 2002). A two-year trial comparing rivastigmine to donepezil in 994 patients with moderate to severe AD found that almost half dropped out, most due to gastrointestinal side effects. Those who continued had a similar benefit with either therapy on measures of cognition and behavior, though rivastigmine appeared to perform slightly better on activities of daily living and global function. Subgroup analyses hinted at better results for rivastigmine in patients with a particular butyrylcholinesterase genotype and patients who had symptoms of concomitant Lewy body disease, as well (Bullock et al, 2005). A two-year observational studyassociated long-term use of rivastigmine with a higher risk of death than long-term use of donepezil (Kazmierski et al., 2018).

Several trials have evaluated rivastigmine for dementia with Lewy bodies and Parkinson's disease dementia. This came up when routine clinical use of cholinesterase inhibitors in dementia patients with symptoms other than typical AD seemed to show a cognitive and clinical benefit in a large minority of such patients (Pakrasi et al., 2003). One multicenter, five-month trial in 120 patients with DLB showed a benefit on apathy, anxiety, delusions, hallucinations, as well as on cognitive performance and attention in the treatment group. About two-thirds of the treated patients had a clinically signifcant response to rivastigmine (McKeith et al., 2000).Based on this and subsequent trials of other cholinesterase inhibitors (see Wang et al, 2014), these medicines are now widely used to treat cognitive and behavioral symptoms in patients with DLB (see Hershey and Coleman-Jackson, 2019).

Hallucinations are a hallmark symptom of DLB and PDD. They represent an area of overlap between these forms of dementia and AD. Retrospective analysis of several trials indicates that AD patients with hallucinations respond better to rivastigmine treatment than those without (Cummings et al., 2010). More broadly, rivastigmine treatment appears to reduce somewhat the concomitant use of antipsychotic medications in people with AD (Scharre et al., 2010). How to manage behavioral symptoms of AD has become a pressing issue since 2005, when the FDA responded with a black-box warning to reports of increased mortality in dementia patients on antipsychotics (see Feb 2011 news;Oct 2005 news).

The EXPRESS (EXelon in PaRkinson's disEaSe dementia Study) trial tested 3 to 12 mg/day of rivastigmine capsules in 541 patients with Parkinson's disease dementia, first for six months in a double-blind and placebo controlled phase, and then in an open-label extension. At six months, treated patients improved modestly on cognition, overall function, and psychiatric symptoms. By 48 weeks, the mean ADAS-cog score for the treatment group remained above baseline, and placebo patients who switched to rivastigmine for the extension phase had a treatment benefit similar to that of the original rivastigmine group during the double-blind trial. Again, patients with hallucinations tended to respond better (e.g.,Poewe et al., 2006). Rivastigmine also appeared to improve apathy in patients with advanced PD who did not yet have dementia; this finding is from a small trial conducted in France (Devos et al., 2014).A university-sponsored trial directly assessed the effect of rivastigmine capsules on hallucinations in people with Parkinson’s. It intended to enroll 168 participants with minor visual hallucinations at baseline, with a primary outcome of time to develop psychosis or dementia. Slow recruitment and lack of funding forced this trial to stop at 91 participants; in this study population rivastigmine did not alter the primary endpoint compared to placebo (van Mierlo et al., 2021).

From 2008-2010, Novartis ran an 18-month trial comparing the capsule and patch formulations in 583 patients with mild to moderately severe PDD. This trial assessed whether long-term treatment with rivastigmine led to worsening of motor symptoms while improving cognitive and psychiatric symptoms of PDD. Traditionally, cholinergic agents have been contraindicated for the motor and autonomic aspects of PD. This is in part because anticholinergic drugs, particularly muscarinic receptor antagonists, have been used for the symptomatic treatment of PD since the late 19th century. According to published results, rivastigmine in this trial caused no additional decline in motor function beyond that expected due to natural disease progression. The most common side effects were nausea, vomiting, and tremor, consistent with other studies (Emre et al., 2014).

Gait stability and falls are related to cholinergic deficits in people with Parkinson’s disease. The Phase 2 Rivastigmine for Gait Stability in Parkinson’s Disease (ReSPonD) trial randomized 130 Parkinson’s patients without dementia, who had fallen at least once in the previous year, to 32 weeks of rivastigmine or placebo. Treatment improved the primary outcome of gait variability (Henderson et al., 2016). A Phase 3 trial running through November 2023 is assessing the effect of a rivastigmine patch on the number of falls over one year in 600 patients. The protocol is published (Neumann et al., 2021).

Some studies indicate that rivastigmine may affect cerebrovascular factors influencing dementia. Alzheimer's patients who also have cardiovascular risk factors such as hypertension have been reported to respond better to rivastigmine than patients with more "pure" Alzheimer's disease, and some evidence exists for a treatment benefit of rivastigmine for vascular dementia (e.g.,Erkinjuntti et al., 2003;Farlow et al., 2011;Birks et al., 2013).A more recent study found no difference in the response to rivastigmine in people with either mild or moderate MRI-documented signs of ischemic damage along with Alzheimer’s (Park et al., 2017).

For some years after cholinesterase inhibitor therapies were initially approved for Alzheimer's disease, their small effect created controversy about cost-effectiveness (see Jul 2004 newsand extensive commentary). Since then, studies have shown that rivastigmine is modestly effective in the long-term treatment of AD, see above. Pharmacoeconomic studies in the United States and European countries have generally found that cholinesterase inhibitor treatment reduces the cost of care (e.g.,Nagy et al., 2011).In the United Kingdom, where this debate had called into question coverage of rivastigmine by this country's universal health care system, NICE in 2011 issued a guidance recommending use of rivastigmine in the treatment of mild to moderate AD (see, e.g.Fillit et al., 1999; Wimo et al., 2003; NICE guidance). In contrast, in May 2018, France’s national health care authority stopped paying for rivastigmine and other cholinesterase inhibitors, claiming an unfavorable risk/benefit ratio for these drugs (see published commentary).

Post-marketing data on long-term safety continues to accrue. According to worldwide adverse-event monitoring systems, rivastigmine was associated with frequent neuropsychiatric and cardiovascular serious adverse events (Krõger et al., 2015). Rivastigmine use was associated with more deaths than other cholinesterase inhibitors (Ali et al., 2015), partly owing to “patch overdose.” This occurs when patients or caregivers apply a new patch without removing the old one, or apply more than one patch at a time (e.g.,Lövborg et al., 2012). Rivastigmine overdose is a medical emergency that can lead to sudden cardiac death.

More recent analysis of data from the FDA Adverse Events Reporting System (FAERS) revealed an apparently increased risk of pneumonia with rivastigmine compared to other symptomatic medications (Morris et al., 2021). This was possibly related to an increase in reports of difficulty swallowing, also in FAERS (Bu et al., 2022). A different study found a slightly increased risk of pneumonia in people using rivastigmine patches, but not capsules, in an analysis of community dwellers with Alzheimer’s disease in Finland (Lampela et al., 2017). However, a study of U.S. Medicare users noted a lower risk of pneumonia among new users of rivastigmine (Lai et al., 2015).

In other trials, rivastigmine decreased postoperative delirium in older people with cognitive dysfunction (e.g.,Youn et al., 2016). It also is suggested to aid recovery after traumatic brain injury, though a recent review calls the evidence for this indication limited (Florentino et al., 2022).

A small trial in 42 children and adolescents with Down's syndrome found no benefit on measures of cognition, language, and overall function (Spiridigliozzi et al., 2016). Trials for cognitive problems in people with multiple sclerosis were likewise negative (Cotter et al., 2018).

In 2018, Novartis began testing the rivastigmine patch in 102 Alzheimer’s patients with severe dementia. The trial, at nine sites in India, will finish in January 2023. An ongoing trial for progressive supranuclear palsy will also end in 2023.

For a list of rivastigmine trials, see clinicaltrials.gov.

Last Updated: 02 Nov 2022

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News Citations

  1. Warning on Antipsychotics Heeded, But What’s the Alternative?
  2. More Trouble for Atypical Antipsychotics—Dementia Patients at Risk
  3. Cholinesterase Inhibitors Not What They're Cracked Up To Be?

Paper Citations

  1. Corey-Bloom J, Anand R, Veach J.For the ENA 713 B352 Study. A randomised 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 Ger Psychopharmacol 1998. 1(2): 155–65.
  2. Rösler M, Anand R, Cicin-Sain A, Gauthier S, Agid Y, Dal-Bianco P, Stähelin HB, Hartman R, Gharabawi M.Efficacy and safety of rivastigmine in patients with Alzheimer's disease: international randomised controlled trial. BMJ. 1999 Mar 6;318(7184):633-8. PubMed.
  3. Winblad B, Grossberg G, Frölich L, Farlow M, Zechner S, Nagel J, Lane R.IDEAL: a 6-month, double-blind, placebo-controlled study of the first skin patch for Alzheimer disease. Neurology. 2007 Jul 24;69(4 Suppl 1):S14-22. PubMed.
  4. Grossberg GT, Olin JT, Somogyi M, Meng X.Dose effects associated with rivastigmine transdermal patch in patients with mild-to-moderate Alzheimer's disease. Int J Clin Pract. 2011 Apr;65(4):465-71. PubMed.
  5. Farlow MR, Grossberg GT, Sadowsky CH, Meng X, Somogyi M.A 24-Week, Randomized, Controlled Trial of Rivastigmine Patch 13.3mg/24h Versus 4.6mg/24h in Severe Alzheimer's Dementia. CNS Neurosci Ther. 2013 Oct;19(10):745-52. PubMed.
  6. Gauthier S, Robillard A, Cohen S, Black S, Sampalis J, Colizza D, de Takacsy F, Schecter R, .Real-life effectiveness and tolerability of the rivastigmine transdermal patch in patients with mild-to-moderate Alzheimer's disease: the EMBRACE study. Curr Med Res Opin. 2013 Aug;29(8):989-1000. PubMed.
  7. Small GW, Kaufer D, Mendiondo MS, Quarg P, Spiegel R.Cognitive performance in Alzheimer's disease patients receiving rivastigmine for up to 5 years. Int J Clin Pract. 2005 Apr;59(4):473-7. PubMed.
  8. Grossberg G, Irwin P, Satlin A, Mesenbrink P, Spiegel R.Rivastigmine in Alzheimer disease: efficacy over two years. Am J Geriatr Psychiatry. 2004 Jul-Aug;12(4):420-31. PubMed.
  9. Wilkinson DG, Passmore AP, Bullock R, Hopker SW, Smith R, Potocnik FC, Maud CM, Engelbrecht I, Hock C, Ieni JR, Bahra RS.A multinational, randomised, 12-week, comparative study of donepezil and rivastigmine in patients with mild to moderate Alzheimer's disease. Int J Clin Pract. 2002 Jul-Aug;56(6):441-6. PubMed.
  10. Bullock R, Touchon J, Bergman H, Gambina G, He Y, Rapatz G, Nagel J, Lane R.Rivastigmine and donepezil treatment in moderate to moderately-severe Alzheimer's disease over a 2-year period. Curr Med Res Opin. 2005 Aug;21(8):1317-27. PubMed.
  11. Kazmierski J, Messini-Zachou C, Gkioka M, Tsolaki M.The Impact of a Long-Term Rivastigmine and Donepezil Treatment on All-Cause Mortality in Patients With Alzheimer's Disease. Am J Alzheimers Dis Other Demen. 2018 Sep;33(6):385-393. Epub 2018 May 9 PubMed.
  12. Pakrasi S, Mukaetova-Ladinska EB, McKeith IG, O'Brien JT.Clinical predictors of response to Acetyl Cholinesterase Inhibitors: experience from routine clinical use in Newcastle. Int J Geriatr Psychiatry. 2003 Oct;18(10):879-86. PubMed.
  13. McKeith I, del Ser T, Spano P, Emre M, Wesnes K, Anand R, Cicin-Sain A, Ferrara R, Spiegel R.Efficacy of rivastigmine in dementia with Lewy bodies: a randomised, double-blind, placebo-controlled international study. Lancet. 2000 Dec 16;356(9247):2031-6. PubMed.
  14. Wang HF, Yu JT, Tang SW, Jiang T, Tan CC, Meng XF, Wang C, Tan MS, Tan L.Efficacy and safety of cholinesterase inhibitors and memantine in cognitive impairment in Parkinson's disease, Parkinson's disease dementia, and dementia with Lewy bodies: systematic review with meta-analysis and trial sequential analysis. J Neurol Neurosurg Psychiatry. 2014 May 14; PubMed.
  15. Hershey LA, Coleman-Jackson R.Pharmacological Management of Dementia with Lewy Bodies. Drugs Aging. 2019 Apr;36(4):309-319. PubMed.
  16. Cummings J, Emre M, Aarsland D, Tekin S, Dronamraju N, Lane R.Effects of rivastigmine in Alzheimer's disease patients with and without hallucinations. J Alzheimers Dis. 2010;20(1):301-11. PubMed.
  17. Scharre DW, Vekeman F, Lefebvre P, Mody-Patel N, Kahler KH, Duh MS.Use of antipsychotic drugs in patients with Alzheimer's disease treated with rivastigmine versus donepezil: a retrospective, parallel-cohort, hypothesis-generating study. Drugs Aging. 2010 Nov 1;27(11):903-13. PubMed.
  18. Poewe W, Wolters E, Emre M, Onofrj M, Hsu C, Tekin S, Lane R, .Long-term benefits of rivastigmine in dementia associated with Parkinson's disease: an active treatment extension study. Mov Disord. 2006 Apr;21(4):456-61. PubMed.
  19. Devos D, Moreau C, Maltête D, Lefaucheur R, Kreisler A, Eusebio A, Defer G, Ouk T, Azulay JP, Krystkowiak P, Witjas T, Delliaux M, Destée A, Duhamel A, Bordet R, Defebvre L, Dujardin K.Rivastigmine in apathetic but dementia and depression-free patients with Parkinson's disease: a double-blind, placebo-controlled, randomised clinical trial. J Neurol Neurosurg Psychiatry. 2014 Jun;85(6):668-74. Epub 2013 Nov 11 PubMed.
  20. van Mierlo TJ, Foncke EM, Post B, Schmand BA, Bloem BR, van Harten B, Tissingh G, Munts AG, de Haan RJ, de Bie RM, other individuals of the CHEVAL Study Group.Rivastigmine for minor visual hallucinations in Parkinson's disease: A randomized controlled trial with 24months follow-up. Brain Behav. 2021 Aug;11(8):e2257. Epub 2021 Jul 21 PubMed.
  21. Emre M, Poewe W, De Deyn PP, Barone P, Kulisevsky J, Pourcher E, van Laar T, Storch A, Micheli F, Burn D, Durif F, Pahwa R, Callegari F, Tenenbaum N, Strohmaier C.Long-term safety of rivastigmine in parkinson disease dementia: an open-label, randomized study. Clin Neuropharmacol. 2014 Jan-Feb;37(1):9-16. PubMed.
  22. Henderson EJ, Lord SR, Brodie MA, Gaunt DM, Lawrence AD, Close JC, Whone AL, Ben-Shlomo Y.Rivastigmine for gait stability in patients with Parkinson's disease (ReSPonD): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Neurol. 2016 Mar;15(3):249-58. Epub 2016 Jan 13 PubMed.
  23. Neumann S, Taylor J, Bamford A, Metcalfe C, Gaunt DM, Whone A, Steeds D, Emmett SR, Hollingworth W, Ben-Shlomo Y, Henderson EJ.Cholinesterase inhibitor to prevent falls in Parkinson's disease (CHIEF-PD) trial: a phase 3 randomised, double-blind placebo-controlled trial of rivastigmine to prevent falls in Parkinson's disease. BMC Neurol. 2021 Oct 29;21(1):422. PubMed.
  24. Erkinjuntti T, Skoog I, Lane R, Andrews C.Potential long-term effects of rivastigmine on disease progression may be linked to drug effects on vascular changes in Alzheimer brains. Int J Clin Pract. 2003 Nov;57(9):756-60. PubMed.
  25. Farlow MR, Doraiswamy PM, Meng X, Cooke K, Somogyi M.The effect of vascular risk factors on the efficacy of rivastigmine patch and capsule treatment in Alzheimer's disease. Dement Geriatr Cogn Dis Extra. 2011 Jan;1(1):150-62. PubMed.
  26. Birks J, McGuinness B, Craig D.Rivastigmine for vascular cognitive impairment. Cochrane Database Syst Rev. 2013;5:CD004744. PubMed.
  27. Park KW, Kim EJ, Han HJ, Shim YS, Kwon JC, Ku BD, Park KH, Yi HA, Kim KK, Yang DW, Lee HW, Kang H, Kwon OD, Kim S, Lee JH, Chung EJ, Park SW, Park MY, Yoon B, Kim BC, Seo SW, Choi SH.Efficacy and tolerability of rivastigmine patch therapy in patients with mild-to-moderate Alzheimer's dementia associated with minimal and moderate ischemic white matter hyperintensities: A multicenter prospective open-label clinical trial. PLoS One. 2017;12(8):e0182123. Epub 2017 Aug 7 PubMed.
  28. Nagy B, Brennan A, Brandtmüller A, Thomas SK, Sullivan SD, Akehurst R.Assessing the cost-effectiveness of the rivastigmine transdermal patch for Alzheimer's disease in the UK using MMSE- and ADL-based models. Int J Geriatr Psychiatry. 2011 May;26(5):483-94. PubMed.
  29. Fillit H, Gutterman EM, Lewis B.Donepezil use in managed Medicare: effect on health care costs and utilization. Clin Ther. 1999 Dec;21(12):2173-85. PubMed.
  30. Wimo A, Winblad B, Engedal K, Soininen H, Verhey F, Waldemar G, Wetterholm AL, Mastey V, Haglund A, Zhang R, Miceli R, Chin W, Subbiah P, Donepezil Nordic Study Group.An economic evaluation of donepezil in mild to moderate Alzheimer's disease: results of a 1-year, double-blind, randomized trial. Dement Geriatr Cogn Disord. 2003;15(1):44-54. PubMed.
  31. Kröger E, Mouls M, Wilchesky M, Berkers M, Carmichael PH, van Marum R, Souverein P, Egberts T, Laroche ML.Adverse Drug Reactions Reported With Cholinesterase Inhibitors: An Analysis of 16 Years of Individual Case Safety Reports From VigiBase. Ann Pharmacother. 2015 Nov;49(11):1197-206. Epub 2015 Aug 31 PubMed.
  32. Ali TB, Schleret TR, Reilly BM, Chen WY, Abagyan R.Adverse Effects of Cholinesterase Inhibitors in Dementia, According to the Pharmacovigilance Databases of the United-States and Canada. PLoS One. 2015;10(12):e0144337. Epub 2015 Dec 7 PubMed.
  33. Lövborg H, Jönsson AK, Hägg S.A fatal outcome after unintentional overdosing of rivastigmine patches. Curr Drug Saf. 2012 Feb;7(1):30-2. PubMed.
  34. Morris R, Umeukeje G, Bu K, Cheng F.The Association Between Use of Rivastigmine and Pneumonia: Systematic Analysis of FDA Adverse Event Reporting System. J Alzheimers Dis. 2021;83(3):1061-1071. PubMed.
  35. Bu K, Patel D, Morris R, Han W, Umeukeje G, Zhu T, Cheng F.Dysphagia Risk in Patients Prescribed Rivastigmine: A Systematic Analysis of FDA Adverse Event Reporting System. J Alzheimers Dis. 2022;89(2):721-731. PubMed.
  36. Lampela P, Tolppanen AM, Tanskanen A, Tiihonen J, Lavikainen P, Hartikainen S, Taipale H.Use of antidementia drugs and risk of pneumonia in older persons with Alzheimer's disease. Ann Med. 2017 May;49(3):230-239. Epub 2016 Nov 29 PubMed.
  37. Lai EC, Wong MB, Iwata I, Zhang Y, Hsieh CY, Kao Yang YH, Setoguchi S.Risk of pneumonia in new users of cholinesterase inhibitors for dementia. J Am Geriatr Soc. 2015 May;63(5):869-76. Epub 2015 Apr 27 PubMed.
  38. Youn YC, Shin HW, Choi BS, Kim S, Lee JY, Ha YC.Rivastigmine patch reduces the incidence of postoperative delirium in older patients with cognitive impairment. Int J Geriatr Psychiatry. 2016 Aug 26; PubMed.
  39. Florentino SA, Bawany MH, Ma HM.Acetylcholinesterase inhibitors to enhance recovery from traumatic brain injury: a comprehensive review and case series. Brain Inj. 2022 Mar 21;36(4):441-454. Epub 2022 Feb 3 PubMed.
  40. Spiridigliozzi GA, Hart SJ, Heller JH, Schneider HE, Baker JA, Weadon C, Capone GT, Kishnani PS.Safety and efficacy of rivastigmine in children with Down syndrome: A double blind placebo controlled trial. Am J Med Genet A. 2016 Jun;170(6):1545-55. Epub 2016 Apr 8 PubMed.
  41. Cotter J, Muhlert N, Talwar A, Granger K.Examining the effectiveness of acetylcholinesterase inhibitors and stimulant-based medications for cognitive dysfunction in multiple sclerosis: A systematic review and meta-analysis. Neurosci Biobehav Rev. 2018 Mar;86:99-107. PubMed.
  42. Cummings J, Lefèvre G, Small G, Appel-Dingemanse S.Pharmacokinetic rationale for the rivastigmine patch. Neurology. 2007 Jul 24;69(4 Suppl 1):S10-3. PubMed.

External Citations

  1. NICE guidance
  2. published commentary
  3. clinicaltrials.gov

News

  1. Barcelona: Taking Parkinson’s Research From Movement to Mind
  2. Common Ground: Is Aβ the Foundation for Multiple Dementias?
  3. Researchers Conclude: Cholinesterase Inhibitors Don’t Delay Alzheimer’s
  4. First Plaque-Based GWAS Revives Enzyme Link

Papers

  1. Aarsland D, Ballard C, Rongve A, Broadstock M, Svenningsson P.Clinical trials of dementia with lewy bodies and Parkinson's disease dementia. Curr Neurol Neurosci Rep. 2012 Oct;12(5):492-501. PubMed.
  2. Anand P, Singh B.A review on cholinesterase inhibitors for Alzheimer's disease. Arch Pharm Res. 2013 Apr;36(4):375-99. PubMed.
  3. Di Santo SG, Prinelli F, Adorni F, Caltagirone C, Musicco M.A meta-analysis of the efficacy of donepezil, rivastigmine, galantamine, and memantine in relation to severity of Alzheimer's disease. J Alzheimers Dis. 2013 Jan 1;35(2):349-61. PubMed.
  4. Bond M, Rogers G, Peters J, Anderson R, Hoyle M, Miners A, Moxham T, Davis S, Thokala P, Wailoo A, Jeffreys M, Hyde C.The effectiveness and cost-effectiveness of donepezil, galantamine, rivastigmine and memantine for the treatment of Alzheimer's disease (review of Technology Appraisal No. 111): a systematic review and economic model. Health Technol Assess. 2012;16(21):1-470. PubMed.
  5. Birks JS, Grimley Evans J.Rivastigmine for Alzheimer's disease. Cochrane Database Syst Rev. 2015 Apr 10;4:CD001191. PubMed.
  6. Patel PH, Gupta V.Rivastigmine. Treasure Island (FL): StatPearls Publishing; 2022 Jul 19. Stat Pearls Publishing
  7. Khoury R, Rajamanickam J, Grossberg GT.An update on the safety of current therapies for Alzheimer's disease: focus on rivastigmine. Ther Adv Drug Saf. 2018 Mar;9(3):171-178. Epub 2018 Jan 8 PubMed.
  8. Masurkar PP, Chatterjee S, Sherer JT, Chen H, Johnson ML, Aparasu RR.Risk of Serious Adverse Events Associated With Individual Cholinesterase Inhibitors Use in Older Adults With Dementia: A Population-Based Cohort Study. Drugs Aging. 2022 Jun;39(6):453-465. Epub 2022 Jun 6 PubMed.
  9. Battle CE, Abdul-Rahim AH, Shenkin SD, Hewitt J, Quinn TJ.Cholinesterase inhibitors for vascular dementia and other vascular cognitive impairments: a network meta-analysis. Cochrane Database Syst Rev. 2021 Feb 22;2:CD013306. PubMed.
  10. Mantri S, Fullard M, Gray SL, Weintraub D, Hubbard RA, Hennessy S, Willis AW.Patterns of Dementia Treatment and Frank Prescribing Errors in Older Adults With Parkinson Disease. JAMA Neurol. 2019 Jan 1;76(1):41-49. PubMed.
  11. McDonald J, Pourcher E, Nadeau A, Corbeil P.A Randomized Trial of Oral and Transdermal Rivastigmine for Postural Instability in Parkinson Disease Dementia. Clin Neuropharmacol. 2018 May/Jun;41(3):87-93. PubMed.
  12. François M, Sicsic J, Pelletier Fleury N.Drugs for Dementia and Excess of Hospitalization: A Longitudinal French Study. J Alzheimers Dis. 2018;61(4):1627-1637. PubMed.
  13. Nieto RA, Deardorff WJ, Grossberg GT.Efficacy of rivastigmine tartrate, transdermal system, in Alzheimer's disease. Expert Opin Pharmacother. 2016;17(6):861-70. PubMed.
  14. Gao W, Ma X, Yang H, Luan Y, Ai H.Molecular engineering and activity improvement of acetylcholinesterase inhibitors: Insights from 3D-QSAR, docking, and molecular dynamics simulation studies. J Mol Graph Model. 2022 Nov;116:108239. Epub 2022 Jun 2 PubMed.
  15. Gayke M, Hirapara N, Narode H, Bhosle SD, Bhosale RS, Yadav JS.Zinc Chloride-Catalyzed Synthesis of Carbamates: An Application for the Synthesis of the Anti-Alzheimer's Drug Rivastigmine. ACS Omega. 2022 Oct 11;7(40):36017-36027. Epub 2022 Sep 26 PubMed.
  16. Sang Z, Bai P, Ban Y, Wang K, Wu A, Mi J, Hu J, Xu R, Zhu G, Wang J, Zhang J, Wang C, Tan Z, Tang L.Novel donepezil-chalcone-rivastigmine hybrids as potential multifunctional anti-Alzheimer's agents: Design, synthesis, in vitro biological evaluation, in vivo and in silico studies. Bioorg Chem. 2022 Oct;127:106007. Epub 2022 Jul 7 PubMed.
  17. Velueta-Viveros M, Martínez-Bailén M, Puerta A, Romero-Hernández LL, Křen V, Merino-Montiel P, Montiel-Smith S, Fernandes MX, Moreno-Vargas AJ, Padrón JM, López Ó, Fernández-Bolaños JG.Carbohydrate-derived bicyclic selenazolines as new dual inhibitors (cholinesterases/OGA) against Alzheimer's disease. Bioorg Chem. 2022 Oct;127:105983. Epub 2022 Jun 25 PubMed.
  18. Khalaf HM, Ahmed SM, Welson NN, Abdelzaher WY.Rivastigmine ameliorates indomethacin experimentally induced gastric mucosal injury via activating α7nAChR with inhibiting oxidative stressand apoptosis. J Biochem Mol Toxicol. 2022 Oct;36(10):e23147. Epub 2022 Jun 15 PubMed.
  19. Huang B, Wang X, Jiang B, Kong L, Hou H, Zhou J.Case Report: A neurolinguistic and neuroimaging study on a Chinese follow-up case with logopenic-variant of primary progressive aphasia. Front Neurol. 2022;13:963970. Epub 2022 Sep 20 PubMed.
  20. Pozzi FE, Conti E, Appollonio I, Ferrarese C, Tremolizzo L.Predictors of response to acetylcholinesterase inhibitors in dementia: A systematic review. Front Neurosci. 2022;16:998224. Epub 2022 Sep 20 PubMed.
Rivastigmine | ALZFORUM (2024)
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