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galantamine (Reminyl, Razadyne, Nivalin)

Tradenames: Reminyl, Nivalin. (galantamine hydrobromide) Reminyl name change to Razadyne* [14] * 3 reported cases of Amaryl (glimepiride) subsitution for Reminyl Extracted from the bulbs of the daffodil, Narcissus pseudonarcissus. Indications: 1) mild to moderate Alzheimer's disease* (FDA approved in 2001) 2) Lewy body dementia 3) vascular dementia [9] See galantamine clinical trials Contraindications: 1) bradycardia 2) hepatic failure 3) renal failure Dosage: 1) start 4 mg PO BID for at least 4 weeks 2) increase to 8 mg PO BID 3) max: 12-16 mg BID 4) Razadyne ER, QD dosing Tabs: 4, 8 & 12 mg Solution: (oral) 4 mg/mL. Razadyne ER: 8, 16, 24 mg Pharmacokinetics: 1) oral bioavailability 90% 2) food delays absorption, but does not affect bioavailability 3) maximal plasma levels of 1.2 ug/mL occur 2 hours after oral administration of 10 mg 4) weak binding to plasma proteins (18%) 5) good penetration of blood brain barrier 6) 95% eliminated in the urine a) 32% eliminated as unchanged galantamine b) 12% eliminated as galantamine glucuronide c) metabolized by cyt P450 2D6 (CYP2D6) & cyt P450 3A4 (CYP3A4) & excreted as glucuronide (1/3) 1] N-oxidation (CYP3A4) 2] 0-demethylation (CYP2D6) 3] at least 1 metabolite has pharmaceutical activity 4] clearance reduced about 25% in poor metabolizers [4] 7) elimination 1/2life is about 5-7 hours Dosage adjustment in renal or hepatic failure: -> dose should not exceed 16 mg/day [4] Adverse effects: 1) diarrhea 2) nausea/vomiting 3) headache 4) dizziness 5) weight loss 6) anorexia 7) bronchoconstriction 8) chest pain (observed frequently during clinical trials) 9) syncope at higher doses (uncommon) 10) bradycardia 11) rivastigmine (RR=1.1) & galantamine (RR=1.5) associated with increased risk of serious adverse events vs donepezil [19] 12) linked to higher mortality (1.5% vs 0.5% for placebo) in 2 trials* [13] * April 1, 2005: Ortho-McNeil Neurologics modified the PRECAUTIONS section of the Prescribing Information for Reminyl (galantamine). Drug interactions: 1) NO interaction with warfarin 2) NO interaction with digoxin 3) potential for drug interactions is low 4) pharmaceutical agents that inhibit CYP2D6 or CYP3A4 may increase levels of galatamine - erythromycin (CYP3A4 inhibitor) increases galantamine (AUC) about 10% [7] 5) pharmaceutical agents that induce CYP3A4 may diminish levels of galatamine 6) cholinergic agents used concurrently with beta-blockers or Ca+2 channel blockers or digoxin may increase risk of bradycardia Mechanism of action: 1) reversible cholinesterase inhibitor 2) may stimulate adrenal gland via cholinesterase inhibition in the splanchnic nerve 3) may allosterically activate nicotinic receptors [6,11,12] -> nicotinic receptor alpha-7 [12] 4) there is no evidence that galantamine alters the course of Alzheimer's disease [7] 5) may symptomatically improve vascular dementia [9] Notes: generic available

Interactions

drug interactions drug adverse effects of cholinesterase inhibitors

Related

galantamine clinical trials

Specific

benzgalantamine; memogain (Zunveyl)

General

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

Properties

MISC-INFO: elimination route KIDNEY 1/2life 5-7 HOURS protein-binding 18%

Database Correlations

PUBCHEM correlations

References

  1. Journal Watch 21(2):18, 2001 Wilcock GK et al, Efficacy and safety of galantamine in patients with mild to moderate Alzheimer's disease: multicentre randomised controlled trial. Galantamine International-1 Study Group. BMJ 321:1445, 2000 PMID: 11110737
  2. Prescriber's Letter 8(5):26 2001
  3. http://www.nivalin.com
  4. Janssen Pharmaceuticals, package insert
  5. Role of cholinergic therapy in treatment of Alzheimer's disease & other dementias, Farlow, M et al, 2001
  6. Small G. In: Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
  7. Raskind MA et al, Galantamine in AD: A 6-month randomized, placebo-controlled trial with a 6-month extension. The Galantamine USA-1 Study Group. Neurology 54:2261, 2000 {clinical trial} PMID: 10881250
  8. Physician's Desk Reference (PDR) 56th edition, Medical Economics, 2002
  9. Journal Watch 22(11):89, 2002 Erkinjuntti T et al, Efficacy of galantamine in probable vascular dementia and Alzheimer's disease combined with cerebrovascular disease: a randomised trial. Lancet 359:1283, 2002 PMID: 11965273 - Schneider LS, Galantamine for vascular dementia: some answers, some questions. Lancet 359:1265, 2002 PMID: 11965268
  10. Olin J & Schneider L, Galantamine for Alzheimer's disease. Cochrane Database Syst Rev. (3):CD001747, 2002 PMID: 12137632
  11. Wilcock GK et al Efficacy and safety of galantamine in patients with mild to moderate Alzheimer's disease: multicentre randomised controlled trial. Galantamine International-1 Study Group. BMJ. 2000 Dec 9;321(7274):1445-9. Erratum in: BMJ 2001 Feb 17; 322(7283):405. PMID: 11110737
  12. Arias E, Ales E, Gabilan NH, Cano-Abad MF, Villarroya M, Garcia AG, Lopez MG. Galantamine prevents apoptosis induced by beta-amyloid and thapsigargin: involvement of nicotinic acetylcholine receptors. Neuropharmacology. 2004 Jan;46(1):103-14. PMID: 14654102
  13. FDA Medwatch http://www.fda.gov/medwatch/SAFETY/2005/safety05.htm#Reminyl
  14. Prescriber's Letter 12(5): 2005 Reminyl Name Changed to Razadyne Detail-Document#: 210502 (subscription needed) http://www.prescribersletter.com
  15. Department of Veterans Affairs, VA National Formulary
  16. Auchis AP et al, Galantamine treatment of vascular dementia: A randomized trial. Neurology 2007, 69:448 PMID: 17664404
  17. Prescriber's Letter 16(10): 2009 Anticipated Availability of First-Time Generics Detail-Document#: 251011 (subscription needed) http://www.prescribersletter.com
  18. Medical Knowledge Self Assessment Program (MKSAP) 17, American College of Physicians, Philadelphia 2015
  19. 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
  20. Highlights of Prescribing Information RAZADYNE (galantamine hydrobromide) tablets/capsules/solution, for oral use https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021615s021lbl.pdf