memantine (Auzura, Namenda, Exiba, Akatinol)
Jump to navigation
Jump to search
Introduction
NMDA receptor antagonist. FDA approved 10/2003 Commercially available outside the US since 1982.
Indications
- treatment of dementia
- including advanced Alzheimer's disease*
- improves clinician's global impression[21]
- may be used in combination with cholinesterase inhibitor [12][16][19]; benefit of combination unclear[22]
- including advanced Alzheimer's disease*
- night time neuropathic pain in diabetic patients
* minimally effective; on list of drugs to avoid[26]
Contraindications
- end-stage renal disease
- not effective for mild Alzheimer's disease*
* NICE does NOT recommend memantine except for clinical trials;
- does NOT delay institutionalization & is NOT cost-effective; OK to continue if currently prescribed medication[18]
Dosage
- start 5 mg PO QD
- increase in 5 mg/day increments to 10 mg PO BID
- divide dose BID
- may be taken with or without food
- maximum dose 20 mg TID
- taper upon discontinuation to avoid potential psychiatric effects[23]
- no evidence to guide decisions about discontinuing memantine[27]
Tabs: 5 & 10 mg (Namenda)
Extended release: 7, 14, 21, 28 mg. QD dosing[24]
Dosage adjustment in renal failure
- no specific recommendations; consider dose reduction
- max dose 5 mg BID for creatinine clearance 5-29 mL/min
Pharmacokinetics
- 10-30 mg of memantine orally achieves serum levels of 0.4-1 uM
- peak serum levels 6-8 hours after oral dose[9]
- 1/2 life 60-100 hours[9]
- protein-binding 10-45%, volume of distribution 9-11 L/kg
- CSF levels 20-30% of serum levels[5] {rats}
- eliminated in the urine
- partial elimination by tubular secretion
elimination via kidney
protein binding = 10-45 %
Adverse effects
- dizziness & agitation same as placebo
- NOT associated with psychosis (other higher affinity NMDA receptor antagonists are associated with psychosis)
- other[6][12] all < 3% relative to placebo
- fatigue, pain, hypertension, dizziness, headache, constipation, back pain, confusion, somnolence, hallucination, cough, dyspnea
- drowsiness, change in behavior[24]
- adverse effects significantly less than those of cholinesterase inhibitors[6]
- case report of seizures
- increases risk for somnolence, weight gain, confusion, hypertension, nervous system disorders, & falls[21]
- increased risk of pneumonia (RR=1.6) relative to donepezil[25]
- supportive measures
- contact poison control
- clearance can be enhanced by acidification of the urine
- after 400 mg of memantine: (1 case report)
- restlessness, psychosis, visual hallucinations, somnolence, stupor, loss of consciousness
- recovery without sequellae
- also see animal toxicity of memantine
Drug interactions
- drugs that alkalinize the urine may decrease clearance of memantine - 80% reduction at pH of 8
- interaction with trimethoprim may increase risk of myoclonus & delirium[24]
- use in combination with other NMDA receptor antagonists has not been evaluated
- NO interaction with cholinesterase inhibitors
Mechanism of action
- low-moderate affinity NMDA receptor antagonist
- reduced need for caregiver assistance[3]; up to 11 hours/week less assistance
* Testing by Forest Laboratories.
Approved & used in several European countries.[8]
Reduced need for caregiver assistance[3]
Merz also producing & testing memantine.
Also see memantine clinical trials
Notes
Cost is slightly less than Aricept[10]
More general terms
Additional terms
Component of
References
- ↑ Ruther et al A prospective PMS study to validate the sensitivity for change of the D-scale in advanced stages of dementia using the NMDA-antagonist memantine. Pharmacopsychiatry 33:103, 2000 PMID: https://www.ncbi.nlm.nih.gov/pubmed/10855461
- ↑ Winblad & Poritis Memantine in severe dementia: results of the 9M-Best Study (Benefit and efficacy in severely demented patients during treatment with memantine). Int J Geriatr Psychiatry 14:135, 1999 PMID: https://www.ncbi.nlm.nih.gov/pubmed/10885864
- ↑ 3.0 3.1 3.2 Journal Watch 23(10):80, 2003 Resiberg B et al mantine in moderate-to-severe Alzheimer's disease. N Engl J Med 348:1333, 2003 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12672860
- ↑ Prescriber's Letter 10(7):40 2003
- ↑ 5.0 5.1 http://www.memantine.com
- ↑ 6.0 6.1 6.2 Prescriber's Letter 10(11) 2003; detail document 191102 http://www.namenda.com
- ↑ Forest Laboratory (Namenda) patient assistance (800) 851-0758
- ↑ 8.0 8.1 Relkin N, 8th International Conference on Alzheimer's Disease & Related Disorders (ICADRC) 2002 http://www.medscape.com/viewarticle/440351
- ↑ 9.0 9.1 9.2 Micromedex
- ↑ 10.0 10.1 Prescriber's Letter 11(2):8 2004 Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=200202&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Areosa SA & Sheriff R, Cochrane Database Syt Rev (3):CD003154, 2003 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12917950 Areosa SA & Sheriff R,Cochrane Database Syst Rev. (1):CD003154, 2003 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12535459
- ↑ 12.0 12.1 12.2 Tariot PN Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA 291:317, 2004 PMID: https://www.ncbi.nlm.nih.gov/pubmed/14734594
- ↑ Department of Veterans Affairs, VA National Formulary
non formulary drug request - ↑ LexiComp
- ↑ Wimo A et al, Resource utilization and cost analysis of memantine in patients with moderate to severe Alzheimer's disease. Pharmacoeconomics 2003, 21:327 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12627986
- ↑ 16.0 16.1 Feldman HH et al, Activites of daily living in moderate-to-severe Alzheimer's disease: an analysis of the treatment effects of memantine in patients receiving stable donepezil treatment. Alzheimer Dis Assoc Disord. 2006, 20:263 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17132971
- ↑ Raina P et al Effectiveness of cholinesterase inhibitors and memantine for treating dementia: evidence review for a clinical practice guideline. Ann Intern Med. 2008 Mar 4;148(5):379-97 PMID: https://www.ncbi.nlm.nih.gov/pubmed/18316756
- ↑ 18.0 18.1 Internal Medicine News, April 15, 2005, pg 12
- ↑ 19.0 19.1 Atri A et al, Long-term course and effectiveness of combination therapy in Alzheimer's disease. Alzheimer Dis Assoc Disord. 2008 Jul-Sep;22(3):209-21. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18580597
- ↑ Schneider LS et al. Lack of evidence for the efficacy of memantine in mild Alzheimer disease. Arch Neurol 2011 Apr 11; <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/21482915 <Internet> http://archneur.ama-assn.org/cgi/content/abstract/archneurol.2011.69v1
- ↑ 21.0 21.1 21.2 Yang Z1, Zhou X, Zhang Q. Effectiveness and safety of memantine treatment for Alzheimer's disease. J Alzheimers Dis. 2013 Jan 1;36(3):445-58. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23635410
- ↑ 22.0 22.1 Muayqil T1, Camicioli R Systematic review and meta-analysis of combination therapy with cholinesterase inhibitors and memantine in Alzheimer's disease and other dementias. Dement Geriatr Cogn Dis Extra. 2012 Jan;2(1):546-72. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23277787
- ↑ 23.0 23.1 Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013
- ↑ 24.0 24.1 24.2 24.3 24.4 Medical Knowledge Self Assessment Program (MKSAP) 17, American College of Physicians, Philadelphia 2015
- ↑ 25.0 25.1 Lampela P, Tolppanen AM, Tanskanen A et al Use of antidementia drugs and risk of pneumonia in older persons with Alzheimer's disease. Ann Med. 2016 Oct 27:1-25. [Epub ahead of print] PMID: https://www.ncbi.nlm.nih.gov/pubmed/27786552
- ↑ 26.0 26.1 Therapeutics Letter #108. Therapeutics Initiative Drugs to Avoid. http://www.ti.ubc.ca/2018/01/04/108-drugs-avoid/
- ↑ 27.0 27.1 Parsons C, Lim WY, Loy C et al Withdrawal or continuation of cholinesterase inhibitors or memantine or both, in people with dementia. Cochrane Database of Systematic Reviews. 2021. Feb 3. Not indexed in PubMed https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD009081.pub2/full
Patient information
memantine (Auzura, Namenda, Exiba, Akatinol) patient information