Rivastigmine

Overview

Rivastigmine, sold under the brand name Exelon among others, is an acetylcholinesterase inhibitor used for the treatment of dementia associated with Alzheimer's disease and with Parkinson's disease. Rivastigmine can be administered orally or via a transdermal patch; the latter form reduces the prevalence of side effects, which typically include nausea and vomiting.[1–5] WP

Rivastigmine is eliminated through the urine, and appears to have relatively few drug-drug interactions.[5] WP

It was patented in 1985 and came into medical use in 1997.[6] WP

Drug class

Acetylcholinesterase inhibitor WP

From the Wikipedia article's infobox.

Uses, dosage and effects

Medical uses

Rivastigmine is indicated for the treatment of mild to moderate Alzheimer's dementia, and for mild to moderate Parkinson's disease dementia. Rivastigmine is available in capsules, liquid solution, and patches.[1][7] WP

Rivastigmine has demonstrated treatment effects on the cognitive (thinking and memory), functional (activities of daily living) and behavioural problems commonly associated with Alzheimer's.[8–11] WP

Efficacy

In people with either type of dementia, rivastigmine has been shown to provide meaningful symptomatic effects that may allow patients to remain independent and 'be themselves' for longer. In particular, it appears to show marked treatment effects in patients showing a more aggressive course of disease, such as those with younger onset ages, poor nutritional status, or those experiencing symptoms such as delusions or hallucinations. For example, the presence of hallucinations appears to be a predictor of especially strong responses to rivastigmine, both in Alzheimer's and Parkinson's patients. These effects might reflect the additional inhibition of butyrylcholinesterase, which is implicated in symptom progression and might provide added benefits over acetylcholinesterase-selective drugs in some patients. Multiple-infarct dementia patients may show slight improvement in executive functions and behaviour. No firm evidence supports usage in schizophrenia patients.[12][13][14] WP

Its efficacy is similar to donepezil and tacrine. Doses below 6 mg/d may be ineffective. The effects of this kind of drug in different kinds of dementia (including Alzheimer's dementia) are modest, and it is still unclear which AChE (BChE) esterase inhibitor is better in Parkinson's dementia, though rivastigmine is well-studied. WP

Administration

Rivastigmine tartrate is a white to off-white, fine crystalline powder that is both lipophilic (soluble in fats) and hydrophilic (soluble in water). It comes in a variety of administrations including a capsule, solution and a transdermal patch. Like other cholinesterase inhibitors, it requires doses to be increased gradually over several weeks; this is usually referred to as the titration phase.[5] WP

Risks and side effects

Side effects

Side effects may include nausea and vomiting, decreased appetite and weight loss.[5] WP

The strong potency of rivastigmine, provided by its dual inhibitory mechanism, has been postulated to lead to more nausea and vomiting during the titration phase of oral rivastigmine treatment.[5] WP

In a large clinical trial of the rivastigmine patch in 1,195 patients with Alzheimer's disease, the target dose of 9.5 mg/24-hour patch provided similar clinical effects (e.g. memory and thinking, activities of daily living, concentration) as the highest doses of rivastigmine capsules, but with one-third fewer reports of nausea and vomiting.[4] WP

Usage of rivastigmine was associated with a higher frequency of reports of death as an adverse event in the Food and Drug Administration Adverse Event Reporting System database compared to the other acetylcholinesterase inhibiting drugs donepezil and galantamine; this increase could be related to improper application of the transdermal patch, or because rivastigmine is more often used during advanced illness.[15] WP

Rivastigmine can increase gastric acid; it is discontinued if there are signs of gastrointestinal bleeding, particularly in individuals using nonsteroidal anti-inflammatory drugs (NSAIDs) or who have a history of peptic ulcer disease.[16] WP

Pharmacology

Pharmacodynamics

Rivastigmine, a cholinesterase inhibitor, inhibits both butyrylcholinesterase and acetylcholinesterase (unlike donepezil, which selectively inhibits acetylcholinesterase). It is thought to work by inhibiting these cholinesterase enzymes, which would otherwise break down the brain neurotransmitter acetylcholine.[17] WP

Pharmacokinetics

When given orally, rivastigmine is well absorbed, with a bioavailability of about 40% in the 3-mg dose. Pharmacokinetics are linear up to 3 mg twice daily, but nonlinear at higher doses. Elimination is through the urine. Peak plasma concentrations are seen in about one hour, with peak cerebrospinal fluid concentrations at 1.4–3.8 hours. When given by once-daily transdermal patch, the pharmacokinetic profile of rivastigmine is much smoother, compared with capsules, with lower peak plasma concentrations and reduced fluctuations. The 9.5 mg/24 h rivastigmine patch provides comparable exposure to 12 mg/day capsules (the highest recommended oral dose).[18] WP

The compound does cross the blood–brain barrier. Plasma protein binding is 40%. The major route of metabolism is by its target enzymes via cholinesterase-mediated hydrolysis. Elimination bypasses the hepatic system, so hepatic cytochrome P450 (CYP) isoenzymes are not involved. The low potential for drug-drug interactions (which could lead to adverse effects) has been suggested as due to this pathway compared to the many common drugs that use the cytochrome P450 metabolic pathway.[5][19][20] WP

A QbD driven HPLC method was developed for the quantification of rivastigmine in rat plasma and brain for its pharmacokinetics study.].[21] WP

History

History

Rivastigmine was developed by Marta Weinstock-Rosin of the Department of Pharmacology at the Hebrew University of Jerusalem and sold to Novartis by Yissum for commercial development. It is a semi-synthetic derivative of physostigmine.[22][23] WP

Chemistry

Formula

C14H22N2O2 PC

CAS number

123441-03-2 PC

Molar mass (g/mol)

250.34 PC

IUPAC name (computed by PubChem)

[3-[(1S)-1-(dimethylamino)ethyl]phenyl] N-ethyl-N-methylcarbamate PC

SMILES

CCN(C)C(=O)OC1=CC=CC(=C1)[C@H](C)N(C)C PC

InChIKey

XSVMFMHYUFZWBK-NSHDSACASA-N PC

PubChem CID

77991

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Journal / agency Exelon- rivastigmine patch, extended release. 8 May 2024
2. Journal / agency Khoury R, Rajamanickam J, Grossberg GT. An update on the safety of current therapies for Alzheimer's disease: focus on rivastigmine. Therapeutic Advances in Drug Safety. March 2018. doi:10.1177/2042098617750555 · PMID 29492246 · PMC5810854
3. Journal / agency Tanner CM, Ostrem JL. Parkinson's Disease. The New England Journal of Medicine. August 2024. doi:10.1056/NEJMra2401857 · PMID 39083773
4. Journal / agency 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. July 2007. doi:10.1212/01.wnl.0000281847.17519.e0 · PMID 17646619
5. Journal / agency Inglis F. The tolerability and safety of cholinesterase inhibitors in the treatment of dementia. International Journal of Clinical Practice. Supplement. June 2002. PMID 12139367
6. Other Fischer J, Ganellin CR. Analogue-based Drug Discovery. 2006
7. Other Recommendations - Parkinson's disease in adults. 2017-07-19
8. Journal / agency 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. International Journal of Geriatric Psychopharmacology. 1998
9. Journal / agency 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. March 1999. doi:10.1136/bmj.318.7184.633 · PMID 10066203 · PMC27767
10. Journal / agency Finkel SI. Effects of rivastigmine on behavioral and psychological symptoms of dementia in Alzheimer's disease. Clinical Therapeutics. July 2004. doi:10.1016/S0149-2918(04)90172-5 · PMID 15336465
11. Journal / agency Rösler M, Retz W, Retz-Junginger P, Dennler HJ. Effects of two-year treatment with the cholinesterase inhibitor rivastigmine on behavioural symptoms in Alzheimer's disease. Behavioural Neurology. 1998. doi:10.1155/1999/168023 · PMID 11568422
12. Journal / agency Gauthier S, Vellas B, Farlow M, Burn D. Aggressive course of disease in dementia. Alzheimer's & Dementia. July 2006. doi:10.1016/j.jalz.2006.03.002 · PMID 19595889
13. Journal / agency Touchon J, Bergman H, Bullock R, Rapatz G, Nagel J, Lane R. Response to rivastigmine or donepezil in Alzheimer's patients with symptoms suggestive of concomitant Lewy body pathology. Current Medical Research and Opinion. January 2006. doi:10.1185/030079906X80279 · PMID 16393430
14. Journal / agency Burn D, Emre M, McKeith I, De Deyn PP, Aarsland D, Hsu C, Lane R. Effects of rivastigmine in patients with and without visual hallucinations in dementia associated with Parkinson's disease. Movement Disorders. November 2006. doi:10.1002/mds.21077 · PMID 16960863
15. Journal / agency 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. doi:10.1371/journal.pone.0144337 · PMID 26642212 · PMC4671709
16. Other Drug monograph: Rivastigmine
17. Journal / agency Camps P, Muñoz-Torrero D. Cholinergic drugs in pharmacotherapy of Alzheimer's disease. Mini Reviews in Medicinal Chemistry. February 2002. doi:10.2174/1389557023406638 · PMID 12369954
18. Journal / agency Cummings J, Lefèvre G, Small G, Appel-Dingemanse S. Pharmacokinetic rationale for the rivastigmine patch. Neurology. July 2007. doi:10.1212/01.wnl.0000281846.40390.50 · PMID 17646618
19. Journal / agency Jann MW, Shirley KL, Small GW. Clinical pharmacokinetics and pharmacodynamics of cholinesterase inhibitors. Clinical Pharmacokinetics. 2002. doi:10.2165/00003088-200241100-00003 · PMID 12162759
20. Journal / agency Jann MW. Rivastigmine, a new-generation cholinesterase inhibitor for the treatment of Alzheimer's disease. Pharmacotherapy. January 2000. doi:10.1592/phco.20.1.1.34664 · PMID 10641971
21. Journal / agency Gopalan D, Patil PH, Jagadish PC, Kini SG, Alex AT, Udupa N, Mutalik S. QbD-driven HPLC method for the quantification of rivastigmine in rat plasma and brain for pharmacokinetics study. Journal of Applied Pharmaceutical Science. 2022-06-05. doi:10.7324/JAPS.2022.120606
22. Other Exelon
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