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  • It is possible to make a diagnosis of AD with as high a degree of certainty as with other neurological and psychiatric disorders
  • Differential diagnosis of AD includes Vascular or multi-infarct dementia Lewy body disease Parkinsonian dementia Pseudodementia due to depression Creutzfeldt-Jakob disease Endocrinopathies and nutritional deficiencies Infectious diseases Metabolic derangements Other neurodegenerative disorders Substance abuse syndrome
  • In the United States alone, there are more than 4 million projected cases of AD Of the more than 4 million patients with AD, only about 50% are diagnosed, and less than 50% of those diagnosed are actually being treated with any type of drug therapy Types of drug therapy included in this analysis are vitamin E, selegiline, ginkgo biloba, and acetylcholinesterase inhibitors (AChEIs) Approximately 12% of patients with AD are currently being treated with an AChEI
  • The associated decline of cognitive function in AD with decreased cholinergic neurotransmission in the cortex, hippocampus, and amygdala is the basis for what is known as the cholinergic hypothesis of AD
  • 9
  • This slide presents the change from baseline in ADAS-cog score over 6 and 12 months in patients with advanced moderate AD as defined by a baseline ADAS-cog score >30. A total of 245 patients treated with REMINYL ® (galantamine HBr) and 257 patients receiving placebo in the 4 randomized clinical trials met this criteria. 1,2 As shown on the graph, ADAS-cog scores were significantly improved in the REMINYL group vs placebo for this patient population (p <0.001). REMINYL-treated patients maintained ADAS-cog scores at or superior to baseline levels during the entire 12 months compared with a significant deterioration of 9.2 points seen in the historical placebo group. 2 Specifically, 51% of REMINYL-treated patients maintained or improved baseline ADAS-cog scores at 12 months compared with 13% of the historical placebo group (p=0.001). 2 References 1. Wilkinson DG, Hock C, Farlow M, van Baelen B, Schwalen S. Galantamine provides broad benefits in patients with “advanced moderate” Alzheimer’s disease (MMSE  12) for up to six months. Int J Clin Pract. 2002;56:509-514. 2. Blesa R, Davidson M, Kurz A, Reichman W, van Baelen B, Schwalen S. Galantamine provides sustained benefits in patients with ‘Advanced Moderate’ Alzheimer’s disease for at least 12 months. Dement Geriatr Cogn Discord . 2003;15:79-87.
  • At Week 52, Reminyl ® (galantamine HBr)-treated patients maintained MMSE scores that were not significantly different compared with baseline, whereas donepezil-treated patients deteriorated significantly from baseline
  • AD can be a treatable disease Treatment with AChEIs has been shown to slow declines in cognition, global function, ADL, and behavior Studies investigating the effects of long-term administration of AChEIs on cognitive performance indicate a consistent benefit of treatment versus no treatment 1-3 Initial response in patients with mild-to-moderate AD may be maintenance of performance or short-term improvement in performance As the disease progresses, benefits of treatment most often are characterized by a slowed rate of functional decline
  • The information in this slide must be presented at the start of every meeting.
  • The clinical significance of these mechanisms is unknown These 2 mechanisms of action are synergistic
  • Nausea and vomiting were typically of mild-to-moderate severity; rates of discontinuation were < 4% for this adverse event Patients who vomited usually had only 1 occurrence, and it tended to coincide with an increase in Reminyl  (galantamine HBr) dose The rates of nausea and vomiting were reduced to baseline levels soon after each dose increase Nausea and vomiting were readily managed by dietary modification, dosing with meals, and use of antiemetics In the open-label extension phase, patients usually regained the weight they lost during the initial phase of the study
  • The pharmacokinetics of Reminyl ® (galantamine HBr) are well suited to its purpose Predictable levels Readily absorbed Active when needed Few drug-drug interactions Low potential for drug-drug interactions Renally excreted
  • This slide summarizes the dosing of Reminyl ® (galantamine HBr) Clear dosing range established Escalation step is 4 weeks 16 mg/day is the target maintenance dose In appropriate patients, 24 mg/day can be used
  • Factors to consider when evaluating the response to galantamine after switching from donepezil or rivastigmine include the half-life of the previous drug, the possibility of additive cholinergic side effects, and the potential for short-term loss of efficacy
  • No data are available to support the use of Reminyl ® (galantamine HBr) in combination with any other AChEI

ReAD04SF.ppt - Medafile.com Home ReAD04SF.ppt - Medafile.com Home Presentation Transcript

  • ALZHEIMER’S DISEASE DIAGNOSIS and TREATMENT J. Wesson Ashford, M.D., Ph.D. Stanford / VA Alzheimer’s Center VAMC, Palo Alto, California San Francisco, California October 5, 2004 Slides at: www.medafile.com (Dr. Ashford’s lectures)
  • Alzheimer Issues
    • Definition of dementia, differential diagnosis
    • Epidemiology (why diagnosis is important)
    • Diagnosis of Alzheimer’s disease (how to)
    • Treatment options
      • The need to treat
      • The benefits of cholinesterase inhibitors
      • The advantage of galantamine (Reminyl)
  • Dementia Definition
    • Multiple Cognitive Deficits:
      • Memory dysfunction
        • especially new learning, a prominent early symptom
      • At least one additional cognitive deficit
        • aphasia, apraxia, agnosia, or executive dysfunction
    • Cognitive Disturbances:
      • Sufficiently severe to cause impairment of occupational or social functioning and
      • Must represent a decline from a previous level of functioning
  • Differential Diagnosis: Top Ten (commonly used mnemonic device: AVDEMENTIA)
    • 1. A lzheimer Disease (pure ~40%, + mixed~70%, ? dLbd)
    • 2. V ascular Disease, MID (5-20%)
    • 3. D rugs, D epression, D elirium
    • 4. E thanol (5-15%)
    • 5. M edical / M etabolic Systems
    • 6. E ndocrine (thyroid, diabetes), E ars, E yes, E nviron.
    • N eurologic (other primary degenerations, fronto-temporal
      • - Consider diffuse Lewy body dementia, Parkinson component)
    • 8. T umor, T oxin, T rauma
    • 9. I nfection, I diopathic, I mmunologic
    • 10. A mnesia, A utoimmune, A pnea, A AMI
    Adapted from Yesavage, 1979
  • Diagnostic Criteria For Dementia Of The Alzheimer Type (DSM-IV, APA, 1994)
    • Multiple Cognitive Deficits
    • 1. Memory Impairment
    • 2. Other Cognitive Impairment
    • B. Deficits Impair Social/Occupational
    • Course Shows Gradual Onset And Decline
    • Deficits Are Not Due to:
    • 1. Other CNS Conditions
    • 2. Substance Induced Conditions
    • E. Do Not Occur Exclusively during Delirium
    • F. Not Due to Another Psychiatric Disorder
  • PREVALENCE of AD
    • Estimated 4 million cases in US (2000)
        • (2000 - 46 million individuals over 60 y/o)
    • Estimated 500,000 new cases per year
    • Increase with age (prevalence)
      • 1% of 60 - 65 (10.7m) = 107,000
      • 2% of 65 - 70 ( 9.4m) = 188,000
      • 4% of 70 - 75 ( 8.7m) = 350,000
      • 8% of 75 - 80 ( 7.4m) = 595,000
      • 16% of 80 - 85 ( 5.0m) = 800,000
  • Total = 281,421,906 >60 = 45,809,291 >65 = 35,003,844 >85 = 4,251,678 >100= 62,545 www.census.gov JW Ashford, MD PhD, 2003
  • www.cdc.gov JW Ashford, MD PhD, 2003
  • JW Ashford, MD PhD, 2003
  • Mortality Equations t = age in years Td = time for mortality rate to double Ro = mortality rate at time zero alpha = ln(2) / Td
    • Mortality rate u(t)
      • R = Ro x exp (alpha x t)
    • Survival curve s(t)
      • S = exp ( - Ro/alpha x (exp (alpha x t) –1 ))
    • Number of deaths per year d(t)
      • D = -ds/dt = ( Ro + alpha x ln (1/s(t) )) x s(t)
      • = u(t) x s(t)
  • JW Ashford, MD PhD, 2003
  • JW Ashford, MD PhD, 2003
  • Genes and Alzheimer’s disease (60% - 80 % of causation)
    • Familial AD (onset < 60 y/o) (<5%)
        • all known autosomal dominant genes relate to  amyloid
      • Presenilin I, II (ch 14, 1)
      • APP (ch 21)
    • Non-familial (late onset)
      • APOE
        • Clinical studies suggest 40 – 50% due to  4
        • If  is considered, may be 95% of causation
        • Population studies suggest 10 – 20% cause
        • Evolution over last 300,000 to 200,000 years
      • At least 20 other genes suspected of relating to AD
    Ashford & Mortimer, 2002, J. Alz. Dis. 4:1-9.
  • APO-E genotype and AD risk 46 Million in US > 60 y/o //// 4 Million have AD (data from Saunders et al., 1993; Farrer et al., 1997) JW Ashford, MD PhD, 2003
  • J. W. Ashford, 2004
  • J. W. Ashford, 2004
  • J. W. Ashford, 2004
  • JW Ashford, MD PhD, 2000
  •  
  • Reprinted with permission from Brumback, RA, Leech RW, J. Ohio State Med Assoc. 1994: 87, 103-111
  • ECONOMIC IMPACT OF AD
    • 2 million AD patients in nursing homes
      • Projection to California – 240,000
    • Nursing homes cost - $120 to $160 per day
    • Annualized cost of nursing homes ranges
      • from $40,000 to $70,000 per year
    • Nursing Home Care of AD patients costs $80 billion per year
      • for life-time cost – about $175,000 per patient
    • The majority of patients live at home and are cared for by family and friends
    • With lost wages of patients and families plus costs for non-nursing home patients:
      • Total costs: $ 120 billion annually ( Am J Publ Hlth )
      • Projection to California – $14.5 billion annually!
  • AD Can Be Readily Diagnosed
    • A diagnosis of Alzheimer’s disease can be made with a high degree of certainty
    • Using NINCDS-ADRDA criteria, accuracy in autopsy-verified cases is approximately 90%
    • Diagnosis is a 2-step process:
      • Detection through screening
      • Confirmation through patient history and physical, caregiver interview, brain imaging, and appropriate laboratory studies
    McKhann G et al. Neurology. 1984;34:939-944. Kazee AM et al. Alzheimer Dis Assoc Disord. 1993;7:152-164. Ashford JW et al, Psychiaric Annals, 1996;26:262-268.
  • AD Is Often Misdiagnosed
    • Patient initially diagnosed with AD
    Source: Consumer Health Sciences, LLC. Alzheimer’s Caregiver Project. 1999. Patient’s first diagnosis other than AD Yes 28% No 72% 21% 7% 9% 14% 14% 35% Normal aging Depression No diagnosis Dementia (not AD) Stroke Other
  • AD is Under-diagnosed
    • Early Alzheimer’s disease is subtle, the diagnosis continues to be missed
      • it is easy for family members to avoid the problem and compensate for the patient
      • physicians tend to miss the initial signs and symptoms
    • Less than half of AD patients are diagnosed
      • Estimates are that 25% to 50% of cases remain undiagnosed
      • Diagnoses are missed at all levels of severity: mild, moderate, severe
    • Undiagnosed AD patients often face avoidable social, financial, and medical problems
    • Early diagnosis and appropriate intervention may lessen disease burden
      • Early treatment may improve overall course substantially
    • No definitive laboratory test for diagnosing AD exists
      • Efforts to develop biomarkers, early recognition by brain scan
    Evans DA. Milbank Quarterly. 1990; 68:267-289
  • Assessment
    • History Of The Development Of The Dementia
      • Ask the Patient What Problem Has Brought Him to See You
      • Ask the Family, Companion about the Problem
      • Specifically Ask about Memory Problems
      • Ask about the First Symptoms
      • Enquire about Time of Onset
      • Ask about Any Unusual Events Around the Time of Onset, e.g., stress, trauma, surgery
      • Ask about Nature and Rate of Progression, Activities of Daily Living
    • Physical Examination
    • Neurological Examination
    • Neuropsychological Assessment
    • Routine Laboratory Tests
    • Brain Scan
  • LABORATORY TESTS (routine)
    • BLOOD TESTS
      • electrolytes, liver, kidney function tests, glucose
      • thyroid function tests (T3, T4, FTI, TSH)
      • vitamin B12, folate
      • complete blood count, ESR
      • VDRL, HIV (if indicated)
    • EKG (if indicated)
    • CHEST X-RAY (if indicated)
    • URINALYSIS
    • ANATOMICAL BRAIN SCAN – CT (cheapest), MRI
  • SPECIAL LABORATORY TESTS
    • FUNCTIONAL BRAIN IMAGING (SPECT, PET – Medicare will pay special cases)
    • EEG, Evoked Potentials (P300)
    • REACTION TIMES (slowed in the elderly, especially when complex response is required
    • CSF ANALYSIS - ROUTINE STUDIES
      • ELEVATED TAU (future possible)
      • DECREASED AMYLOID (future possible)
    • HEAVY METAL SCREEN (24 hr urine)
    • GENOTYPING
      • APO-LIPOPROTEIN-E (for supporting dx)
      • AUTOSOMAL DOMINANT (young onset)
  • Why Diagnose AD Early?
    • Safety (driving, compliance, cooking, etc.)
    • Family stress and misunderstanding (blame, denial)
    • Early education of caregivers of how to handle patient (choices, getting started)
    • Advance planning while patient is competent (will, proxy, power of attorney, advance directives)
    • Patient’s and Family’s right to know
    • Promotes advocacy for research and treatment development
    • Specific treatments now available
      • May slow underlying disease process, the sooner the better
      • May delay nursing home placement longer if started earlier
      • May prevent conversion from Mild Cognitive Impairment to AD
  • AAMI / MCI/ early AD -- DEMENTIA ALZHEIMER’S DISEASE Ashford et al., 1995
  • Need to Develop Better Screening and Early Assessment Tools
    • Genetic vulnerability testing (trait risk)
    • Vulnerability factors (education, occupation, head injury)
    • Early recognition (10 warning signs)
    • Screening tools (6th vital sign in elderly)
    • Positive diagnostic tests
      • CSF – tau levels elevated, amyloid levels low
      • Brain scan – PET – DDNP, Congo-red derivatives
    • Mild Dementia severity assessments
    • Detecting early change over time
      • predicting progression, measuring rate
  • Alzheimer Warning Signs Top Ten Alzheimer Association
    • 1. Recent memory loss affecting job
    • 2. Difficulty performing familiar tasks
    • 3. Problems with language
    • 4. Disorientation to time or place
    • 5. Poor or decreased judgment
    • 6. Problems with abstract thinking
    • 7. Misplacing things
    • 8. Changes in mood or behavior
    • 9. Changes in personality
    • 10. Loss of initiative
  • Need for a Brief Screening Test for Dementia, Alzheimer’s Disease
    • Recent evidence of benefits of anti-cholinesterase agents in the treatment of mild Alzheimer’s disease
      • Improvement of cognition
      • Slowing of progression
      • Delay of conversion to diagnosis
    • How to get elderly, clinicians interested in screening for dementia
    • How to handle positive screens sensitively and efficiently
      • Doctors have been reluctant to diagnose Alzheimer’s disease because of the time required to explain the problem to the family and to coordinate treatment.
  • Brief Alzheimer Screen (BAS)
    • Repeat these three words: “apple, table, penny”.
    • So you will remember these words, repeat them again.
    • What is today’s date?
        • D = 1 if within 2 days.
    • Spell the word “WORLD” backwards
        • S = 1 point for each word in correct order
    • “ Name as many animals as you can in 30 seconds, GO!”
        • A = number of animals
    • “ What were the 3 words I asked you to repeat?” (no prompts)
        • R = 1 point for each word recalled
    • B AS = 3 x R + 2/3 x A + 5 x D + 2 x S
    • (Mendiondo et al., 2003)
  • Dementia Screening Test
    • Need test to screen patients for Alzheimer’s disease
    • Test needs to be on multiple platforms:
      • Doctor’s offices
      • Best if computerized for rapid, objective assessment
      • World-Wide Web – based testing,
      • CD-distribution
      • KIOSK administration – drug stores, shopping malls
    • Test needs to be very brief (about 1-minute)
    • Multiple test forms needed so it can be repeated often (quarterly)
    • Screening should be done yearly after age 50, and repeated every 3 months for individuals over 65 years of age or with concerns
    • Any change over time needs to be detected
    • The test should be free
  • MEMTRAX - Memory Test (to detect AD onset)
    • New test to screen patients for AD:
      • World-Wide Web – based testing,
      • CD-distribution
      • KIOSK administration
    • Determine level of ability / impairment
    • Test takes about 1-minute
    • Test can be repeated often (e.g., quarterly)
    • Any change over time can be detected
    • Free test is at: www.medafile.com
  • FIRST SUCCESSFUL TREATMENT:
    • CHOLINESTERASE INHIBITION
        • (1st double blind study - Ashford et al., 1981)
      • Presumably increases acetylcholine at synapses
      • Improvement in cognition (? 6-12 months better)
      • Improvement in function (ADLs, variable)
      • Improvement in behavior (? basal ganglia)
      • Slowing of disease course
        • Treatment delays nursing home placement
        • There is loss of benefit with delay of treatment
      • Need to consider early intervention
  • Treatment of Alzheimer’s Disease Source: Decision Resources, March 2000. * Any drug treatment, not limited to acetylcholinesterase inhibitors. 0 1 2 3 4 5 Patients (millions) Prevalence 4,523,100 Diagnosed 2,261,600 Treated with AChEIs 543,800 Treated* 904,600
  •  
  • Cholinergic Changes in AD
    • The most prominent neurotransmitter abnormalities are cholinergic
      • Reduced activity of choline acetyltransferase (synthesis of acetylcholine) 1
    • Reduced number of cholinergic neurons in late AD (particularly in basal forebrain) 2
    • Selective loss of nicotinic receptor subtypes in hippocampus and cortex 1,3
    1. Bartus RT et al. Science . 1982;217:408-414. 2. Whitehouse PJ et al. Science. 1982;215:1237-1239. 3. Guan ZZ et al. J Neurochem . 2000;74:237-243.
  •  
  • Stimulated by acetylcholine through muscarinic receptor Favored when lipid raft too large Lipid raft Formed by cholesterol Transported by ApoE From macroglia intracellular extra cellular NEXIN ? To establish new connections ? Free-radical generator ? To remove old synapses JW Ashford, MD PhD, 2003
  • Need to divide effects of drug treatment into 2 groups
    • Acute effects of treatment
      • e.g., 3 months
      • are the acute effects related to severity?
        • e.g., do AChEases may work very well in mild patients,
        • and in nursing home patients?
        • do these medications work in very early phases of the disease?
    • Chronic effects of treatment
      • rate of change, after acute effects
      • are the effects on rate of change related to severity
        • are very mild patients improved over time by AChEases?
        • are new AChEase molecules created which require dose increases?
        • does sudden discontinuation lead to catastrophic decline?
      • do early, chronic benefits suggest prevention?
  •  
  • Exelon  Improves Cognitive Function: ADAS-Cog mean change from baseline † Mean change in ADAS-Cog score Improvement Worsening 12 18 26 Weeks * * * 6–12 mg/day Exelon ® 1–4 mg/day Exelon ® Placebo * * † B352 OC study analysis; *p<0.05 vs placebo 4.94 2 1 0 – 1 – 2 – 3 – 4 – 5 Corey-Bloom J et al, for the ENA 713 B352 Study Group. Int J Geriatr Psychopharmacol. 1998;1:55-65.
  • Exelon  Longterm Effects on Cognition: Mean Change in ADAS-Cog from Baseline at Week 52 All Patients Taking Exelon B352 Patients in B353 (OC) at Week 52 * * * * p< 0.05 vs projected placebo * * * * * * Sohn et al. In: Proceedings of the CPNP. April 2000.
  •  
  •  
  • REMINYL ® (galantamine HBr) Pooled Analysis: Change in ADAS-cog Scores at 6 and 12 Months Advanced Moderate AD Patients With Baseline ADAS-cog Scores >30 Adapted from Blesa R et al. Dement Geriatr Cogn Discord. 2003;15:79-87. *p<0.001 vs placebo. † p<0.001 vs historical placebo. ‡ Not significant vs baseline. Baseline ADAS-cog score: 37.3 (REMINYL 24 mg/d) vs 37.4 (placebo). Improvement Mean (  SE) Change in ADAS-cog From Baseline – 8 – 6 – 4 – 2 0 2 4 6 8 10 12 Baseline 1 3 6 9 12 Time (mo) † ‡ REMINYL 24 mg/d Placebo from RCTs Historical placebo * * * †
  •  
  •  
  •  
  • GAL-GBR-2 MMSE: Change From Baseline * p  0.0001 vs baseline; † p = 0.0006 vs baseline; # p = 0.0003 vs baseline. NS = p > 0.1. – 2.5 – 2 – 1.5 – 1 – 0.5 0 0.5 1 1.5 2 2.5 Mean MMSE change (± SE) from baseline † # * * NS Reminyl ® (galantamine HBr) (n = 94) Aricept ® (n = 87) Weeks 0 13 26 39 52 Data on file, Janssen Pharmaceutica Products, L.P. Bullock R et al. Poster presented at the 41st Annual Meeting of the ACNP, San Juan, Puerto Rico, December 8–12, 2002. .
  • Benefits of Treatment of AD With Acetylcholinesterase Inhibitors
    • AChEIs may improve, maintain, or slow the decline of cognitive, behavioral, and functional performance in patients with mild-to-moderate AD
    • Delay of treatment leads to loss of potential benefit
    • AChEIs may delay nursing home placement over 20 months, and potentially much more when started early.
    • AChEIs have demonstrated consistent efficacy and safety in maintaining cognitive function, as measured by ADAS-cog in patients with mild-to-moderate AD for up to 1 year – relative to placebo!!
          • Donepezil 1 38 weeks
          • Rivastigmine 2 38–42 weeks
          • Galantamine 3 52 weeks (25-30% better)
    1. Rogers SL et al. Eur Neuropsychopharmacol . 2000;10:195-203. 2. Farlow M et al. Eur Neurol . 2000;44:236-241. 3. Raskind MA et al. Neurology. 2000;54:2261-2268.
  • Indications
    • REMINYL ® (galantamine HBr) is approved for the treatment of patients with mild-to-moderate dementia of the Alzheimer’s type
    • The most frequent adverse events associated with REMINYL included nausea, vomiting, diarrhea, anorexia, and weight loss; most were generally transient and mild to moderate in severity
    • REMINYL is available in 4-mg, 8-mg and 12-mg tablets and an oral solution (4 mg/mL) and is taken twice a day, preferably with morning and evening meals
    • May benefit very early cases, particular APOE-e4 carriers
  • Reminyl ® (galantamine HBr): Proposed Mechanisms of Action
    • Increases amount of acetylcholine available in synaptic cleft by inhibiting breakdown of acetylcholine
    • By modulating activity at nicotinic receptors, it may increase release of acetylcholine from surviving presynaptic nerve terminals
    • Combination action may diminish cholinesterase supersensitivity from developing, prolonging the benefit.
    • May provide greatest delay of illness progression
    • May require increase of dose after patient declines below initial baseline, to maintain benefit for longer term.
    Maelicke A, Albuquerque EX. Eur J Pharmacol. 2000;393:165-170.
  • Reminyl ® (galantamine HBr) GI Tolerability
    • Nausea and vomiting: typically transient and related to treatment initiation and dose escalation
      • Among patients experiencing nausea, median duration was 5 to 7 days
    • Weight loss: reported as an adverse event in  5% of patients, with none discontinuing treatment due to weight loss
    REMINYL Full Prescribing Information, 2001. Data on file, Janssen Pharmaceutica Products, L.P.
  • Reminyl ® (galantamine HBr) Pharmacokinetics
    • Linear pharmacokinetics
    • Bioavailability: 90%
    • Half-life: 7 hours
      • - can provide decrease inhibition at night!!
    • Low (18%) plasma protein binding
    • Hepatic metabolism via multiple pathways, primarily CYP2D6 and CYP3A4
    • Renal excretion
  • Reminyl ® (galantamine HBr): Dosing
    • Simple, one-step dose escalation
      • 8 mg/day starting dose
        • for 4 weeks (4 mg bid)
      • 16 mg/day maintenance dose
        • for at least 4 weeks (8 mg bid)
      • The flexibility to increase to 24 mg/day
        • (12 mg bid) – should try after 12 weeks if further benefit sought
    • Taken preferably with morning and evening meals
      • Later, better with morning meal, mid-afternoon snack.
      • (Avoid nocturnal cholinergic activation!!)
    • Available in 4-mg, 8-mg, and 12-mg tablets and oral solution (4 mg/mL)
  • Switching Guidelines (cont)
    • Switching from Aricept ® to Reminyl ® (galantamine HBr)
      • No washout period of Aricept ® should be undertaken before initiating REMINYL. The standard dose escalation should be undertaken the next day after the last Aricept ® administration
    • Switching from Exelon ® to REMINYL
      • No washout period of Exelon ® should be undertaken before initiating REMINYL. The standard dose escalation should be undertaken the next day after the last Exelon ® administration
    Morris JC et al. Clin Ther . 2001;23(suppl A):A31-39.
  • Switching guidelines (cont)
    • Exceptions
      • For patients who are experiencing poor tolerability on Aricept ® or Exelon ® , a washout period of up to 7 days should be undertaken, or until symptoms resolve
      • The standard dose escalation of Reminyl ® (galantamine HBr) should then be undertaken
    • Combined dosing
      • Combination therapy with AChEIs is not recommended by the manufacturing company
      • Galantamine may be combined with Namenda ® (memantine)
        • Evidence suggests additional efficacy
        • Combination appears to be at least as effective as combination of donepezil and memantine
    Morris JC et al. Clin Ther . 2001;23(suppl A):A31-39.