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rivastigmine (Exelon)

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: - bradycardia * of no value in treatment of vascular dementia [11] Dosage: 1) 1.5-6 mg PO BID 2) start: 1.5 mg PO BID with food 3) administration with food & slow titration is likely to reduce incidence of adverse effects 4) 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: 1) well absorbed with bioavailability of 40% (3 mg dose) -> food delays & increases absorption & reduces nausea 2) peak plasma concentrations are reached in 1 hour 3) widely distributed: a) volume of distribution is 1.8-2.7 L/kg b) penetrates blood-brain barrier -> maximum CSF cholinesterase inhibition of 60%, 5 hours after 6 mg oral dose 4) 40% is bound to plasma proteins 5) metabolized by cholinesterase to decarbamylated derivative NAP 226-90 a) minimal involvement of the cyt P450 system b) NAP 266-90 may undergo demethylation &/or sulfation 6) 40% of elimination occurs in the urine as sulfate conjugate of decarbamylated metabolite [6] 7) elimination 1/2 life is 1.5 hours 8) higher doses may be more effective Adverse effects: (likely to be transient @ 6-12 mg/day) 1) cholinergic side effects a) nausea (35%); median duration 8-11 days b) vomiting (25%); median duration 2-3 days c) diarrhea d) abdominal pain, dyspepsia e) weight loss f) bronchoconstriction g) asthenia h) bradycardia 2) dizziness 3) headache 4) syncope 5) rivastigmine (RR=1.1) & galantamine (RR=1.5) associated with increased risk of serious adverse events vs donepezil [13] Drug interactions: 1) not likely to interact with other drugs 2) cholinergic agents used concurrently with beta-blockers or Ca+2 channel blockers or digoxin may increase risk of bradycardia 3) smoking increases clearance of rivastigmine (up to 20%) Mechanism of action: 1) reversible inhibition of acetylcholinesterase 2) reversible inhibition of butyrylcholinesterase 3) brain selective [3] -> selectivity for cerebral cortex & hippocampus [3] 4) no evidence that rivastigmine alters the course of Alzheimer's disease [6]

Interactions

drug interactions drug adverse effects of cholinesterase inhibitors

Related

Alzheimer's disease (AD) rivastigmine clinical trials

General

pharmaceutical agents for treatment of Alzheimer's disease (Alzheimer's agent) cholinesterase inhibitor

Properties

SIZE: MW = 400 G/MOLE MISC-INFO: elimination route LIVER KIDNEY 1/2life 1.5 HOURS protein-binding 40% pregnancy-category B safety in lactation ?

Database Correlations

PUBCHEM correlations

References

  1. Prescriber's Letter 7(5):28, May 2000
  2. Novartis Pharmaceuticals Corporation
  3. Role of cholinergic therapy in treatment of Alzheimer's disease & other dementias, Farlow, M et al, 2001
  4. Geriatric Dosage Handbook, 6th edition, Selma et al eds, Lexi-Comp, Cleveland, 2001
  5. Birks et al, Rivastigmine for Alzheimer's disease (Cochrane Review). In: The Cochrane Library, 2, 2001
  6. Physician's Desk Reference (PDR) 56th edition, Medical Economics, 2002
  7. Prescriber's Letter 14(9): 2007 New dosage form: (Exelon (rivastigmine) patch Detail-Document#: 230908 (subscription needed) http://www.prescribersletter.com
  8. Deprecated Reference
  9. Medical Knowledge Self Assessment Program (MKSAP) 17, American College of Physicians, Philadelphia 2015
  10. 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 PMID: 26795874 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 PMID: 26795875 http://thelancet.com/journals/laneur/article/PIIS1474-4422%2816%2900003-X/abstract
  11. 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: 18674411
  12. Espay AJ et al. Rivastigmine in Parkinson's disease dementia with orthostatic hypotension. Ann Neurol 2020 Oct 5; PMID: 33016374 https://onlinelibrary.wiley.com/doi/10.1002/ana.25923
  13. 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: 35666463 https://link.springer.com/article/10.1007/s40266-022-00944-z