rivastigmine (Exelon)
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Introduction
Tradenames: Exelon.
Indications
- Alzheimer's dementia (FDA approved in 2000)
- Lewy body dementia
- Parkinson's dementia[8][9]
- cognitive benefits more pronounced when orthostatic hypotension is present[12]
- rivastigmine may improve gait stability & reduce risk of falls in patients with Parkinson's disease (RR=0.58)[10]
Contraindications
* of no value in treatment of vascular dementia[11]
Dosage
- 1.5-6 mg PO BID
- start: 1.5 mg PO BID with food
- administration with food & slow titration is likely to reduce incidence of adverse effects
- increase to 6 mg PO BID as tolerated
Capsules: 1.5, 3, 4.5 & 6 mg
Solution: (oral) 2 mg/mL
Transdermal patch: 4.6, 9 & 13.3 mg, change patch daily[7][9]
Pharmacokinetics
- well absorbed with bioavailability of 40% (3 mg dose)
- food delays & increases absorption & reduces nausea
- peak plasma concentrations are reached in 1 hour
- widely distributed:
- volume of distribution is 1.8-2.7 L/kg
- penetrates blood-brain barrier
- maximum CSF cholinesterase inhibition of 60%, 5 hours after 6 mg oral dose
- 40% is bound to plasma proteins
- metabolized by cholinesterase to decarbamylated derivative NAP 226-90
- minimal involvement of the cyt P450 system
- NAP 266-90 may undergo demethylation &/or sulfation
- 40% of elimination occurs in the urine as sulfate conjugate of decarbamylated metabolite[6]
- elimination 1/2 life is 1.5 hours
- higher doses may be more effective
elimination via liver
elimination via kidney
1/2life = 1.5 hours
protein binding = 40 %
Adverse effects
(likely to be transient @ 6-12 mg/day)
- cholinergic side effects
- nausea (35%); median duration 8-11 days
- vomiting (25%); median duration 2-3 days
- diarrhea
- abdominal pain, dyspepsia
- weight loss
- bronchoconstriction
- asthenia
- bradycardia
- dizziness
- headache
- syncope
- rivastigmine (RR=1.1) & galantamine (RR=1.5) associated with increased risk of serious adverse events vs donepezil[13]
Drug interactions
- not likely to interact with other drugs
- cholinergic agents used concurrently with beta-blockers or Ca+2 channel blockers or digoxin may increase risk of bradycardia
- smoking increases clearance of rivastigmine (up to 20%)
- drug interaction(s) of haloperidol with rivastigmine
- drug interaction(s) of cholinesterase inhibitors with NSAIDs
- drug interaction(s) of parasympatholytic with parasympathomimetic
Mechanism of action
- reversible inhibition of acetylcholinesterase
- reversible inhibition of butyrylcholinesterase
- brain selective[3]
- selectivity for cerebral cortex & hippocampus[3]
- no evidence that rivastigmine alters the course of Alzheimer's disease[6]
More general terms
Additional terms
References
- ↑ Prescriber's Letter 7(5):28, May 2000
- ↑ Novartis Pharmaceuticals Corporation
- ↑ 3.0 3.1 3.2 Role of cholinergic therapy in treatment of Alzheimer's disease & other dementias, Farlow, M et al, 2001
- ↑ Geriatric Dosage Handbook, 6th edition, Selma et al eds, Lexi-Comp, Cleveland, 2001
- ↑ Birks et al, Rivastigmine for Alzheimer's disease (Cochrane Review). In: The Cochrane Library, 2, 2001
- ↑ 6.0 6.1 6.2 Physician's Desk Reference (PDR) 56th edition, Medical Economics, 2002
- ↑ 7.0 7.1 Prescriber's Letter 14(9): 2007 New dosage form: (Exelon (rivastigmine) patch Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=230908&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 8.0 8.1 Deprecated Reference
- ↑ 9.0 9.1 9.2 Medical Knowledge Self Assessment Program (MKSAP) 17, American College of Physicians, Philadelphia 2015
- ↑ 10.0 10.1 Henderson EJ, Lord SR, Brodie MA et al Rivastigmine for gait stability in patients with Parkinson's disease (ReSPonD): a randomised, double-blind, placebo- controlled, phase 2 trial. Lancet Neurology. Jan 12, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26795874 <Internet> http://thelancet.com/journals/laneur/article/PIIS1474-4422%2815%2900389-0/abstract
Moreau C, Devos D, Defebvre L Acetylcholinesterase inhibitors and gait: a steadying hand? Lancet Neurology. Jan 12, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26795875 <Internet> http://thelancet.com/journals/laneur/article/PIIS1474-4422%2816%2900003-X/abstract - ↑ 11.0 11.1 Ballard C, Sauter M, Scheltens P et al Efficacy, safety and tolerability of rivastigmine capsules in patients with probable vascular dementia: the VantagE study. Curr Med Res Opin. 2008 Sep;24(9):2561-74. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18674411
- ↑ 12.0 12.1 Espay AJ et al. Rivastigmine in Parkinson's disease dementia with orthostatic hypotension. Ann Neurol 2020 Oct 5; PMID: https://www.ncbi.nlm.nih.gov/pubmed/33016374 https://onlinelibrary.wiley.com/doi/10.1002/ana.25923
- ↑ 13.0 13.1 Masurkar PP, Chatterjee S, Sherer JT et al. Risk of Serious Adverse Events Associated With Individual Cholinesterase Inhibitors Use in Older Adults With Dementia: A Population-Based Cohort Study. Drugs Aging 2022. June 6 PMID: https://www.ncbi.nlm.nih.gov/pubmed/35666463 https://link.springer.com/article/10.1007/s40266-022-00944-z