galantamine (Reminyl, Razadyne, Nivalin)
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Introduction
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
- mild to moderate Alzheimer's disease* (FDA approved in 2001)
- Lewy body dementia
- vascular dementia[9]
See galantamine clinical trials
Contraindications
Dosage
- start 4 mg PO BID for at least 4 weeks
- increase to 8 mg PO BID
- max: 12-16 mg BID
- Razadyne ER, QD dosing
Tabs: 4, 8 & 12 mg
Solution: (oral) 4 mg/mL. Razadyne ER: 8, 16, 24 mg
Pharmacokinetics
- oral bioavailability 90%
- food delays absorption, but does not affect bioavailability
- maximal plasma levels of 1.2 ug/mL occur 2 hours after oral administration of 10 mg
- weak binding to plasma proteins (18%)
- good penetration of blood brain barrier
- 95% eliminated in the urine
- 32% eliminated as unchanged galantamine
- 12% eliminated as galantamine glucuronide
- metabolized by cyt P450 2D6 (CYP2D6) & cyt P450 3A4 (CYP3A4) & excreted as glucuronide (1/3)
- N-oxidation (CYP3A4)
- 0-demethylation (CYP2D6)
- at least 1 metabolite has pharmaceutical activity
- clearance reduced about 25% in poor metabolizers[4]
- elimination 1/2life is about 5-7 hours Dosage adjustment in renal or hepatic failure:
elimination via kidney
1/2life = 5-7 hours
protein binding = 18 %
Adverse effects
- diarrhea
- nausea/vomiting
- headache
- dizziness
- weight loss
- anorexia
- bronchoconstriction
- chest pain (observed frequently during clinical trials)
- syncope at higher doses (uncommon)
- bradycardia
- rivastigmine (RR=1.1) & galantamine (RR=1.5) associated with increased risk of serious adverse events vs donepezil[19]
- 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
- NO interaction with warfarin
- NO interaction with digoxin
- potential for drug interactions is low
- pharmaceutical agents that inhibit CYP2D6 or CYP3A4 may increase levels of galatamine
- erythromycin (CYP3A4 inhibitor) increases galantamine (AUC) about 10%[7]
- pharmaceutical agents that induce CYP3A4 may diminish levels of galatamine
- cholinergic agents used concurrently with beta-blockers or Ca+2 channel blockers or digoxin may increase risk of bradycardia
- drug interaction(s) of cholinesterase inhibitors with NSAIDs
- drug interaction(s) of parasympatholytic with parasympathomimetic
Mechanism of action
- reversible cholinesterase inhibitor
- may stimulate adrenal gland via cholinesterase inhibition in the splanchnic nerve
- may allosterically activate nicotinic receptors[6][11][12]
- there is no evidence that galantamine alters the course of Alzheimer's disease[7]
- may symptomatically improve vascular dementia[9]
Notes
generic available
More general terms
Additional terms
References
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/11110737
- ↑ Prescriber's Letter 8(5):26 2001
- ↑ http://www.nivalin.com
- ↑ 4.0 4.1 4.2 Janssen Pharmaceuticals, package insert
- ↑ Role of cholinergic therapy in treatment of Alzheimer's disease & other dementias, Farlow, M et al, 2001
- ↑ 6.0 6.1 Small G. In: Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
- ↑ 7.0 7.1 7.2 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: https://www.ncbi.nlm.nih.gov/pubmed/10881250
- ↑ Physician's Desk Reference (PDR) 56th edition, Medical Economics, 2002
- ↑ 9.0 9.1 9.2 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: https://www.ncbi.nlm.nih.gov/pubmed/11965273
Schneider LS, Galantamine for vascular dementia: some answers, some questions. Lancet 359:1265, 2002 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11965268 - ↑ Olin J & Schneider L, Galantamine for Alzheimer's disease. Cochrane Database Syst Rev. (3):CD001747, 2002 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12137632
- ↑ 11.0 11.1 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: https://www.ncbi.nlm.nih.gov/pubmed/11110737
- ↑ 12.0 12.1 12.2 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: https://www.ncbi.nlm.nih.gov/pubmed/14654102
- ↑ 13.0 13.1 FDA Medwatch http://www.fda.gov/medwatch/SAFETY/2005/safety05.htm#Reminyl
- ↑ 14.0 14.1 Prescriber's Letter 12(5): 2005 Reminyl Name Changed to Razadyne Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=210502&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Department of Veterans Affairs, VA National Formulary
- ↑ Auchis AP et al, Galantamine treatment of vascular dementia: A randomized trial. Neurology 2007, 69:448 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17664404
- ↑ Prescriber's Letter 16(10): 2009 Anticipated Availability of First-Time Generics Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=251011&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Medical Knowledge Self Assessment Program (MKSAP) 17, American College of Physicians, Philadelphia 2015
- ↑ 19.0 19.1 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
- ↑ Highlights of Prescribing Information RAZADYNE (galantamine hydrobromide) tablets/capsules/solution, for oral use https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021615s021lbl.pdf