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Is Aricept 23mg beneficial?
JAB
Posted: Friday, January 6, 2012 1:13 PM
Joined: 11/30/2011
Posts: 740


Lemonade posted this question on Solutions ... but there just isn't room enough there to give a good answer.  Plus, it isn't possible to format links etc.  So, lemonade, I'm answering you here.

 
First off, please note that (a) a loved one should stable be on the 10mg pills for at least six weeks before thinking of increasing the dosage, and (b) FDA approval was for patients with more advanced (moderate to severe) Alzheimer's.

 

Even under those conditions, whether Aricept 23mg would be beneficial or instead cause serious adverse effects will very much depend on your loved one.

 

For example, recent studies indicate that the therapeutic responses to this drug may be due to subtle differences in certain genes. Aricept is metabolized via CYP-related enzymes in the liver, especially CYP2D6, CYP3A4, and CYP1A2. Approximately 15-20% of Alzheimer’s patients may exhibit an abnormal metabolism of Aricept. Of these, ~50% show an ultra-rapid metabolism, requiring higher doses of the drug to reach a therapeutic threshold, whereas the other 50% show a poor metabolism, exhibiting adverse side effects at low doses.  Pharmacogenetic and pharmacogenomic factors may account for 75-85% of the therapeutic response to ChEIs that are metabolized via liver enzymes of the CYP family.  See: 
http://www.alzcompend.info/?p=244

Moreover, in reading the FDA review of the drug company's application for approval, I noticed some very interesting points I hadn't seen before, i.e., that age, gender, and body weight can have a huge impact on the overall dose a loved one receives.  E.g.:

 

"The steady-state exposure (AUCss) of donepezil was about 35% higher in patients than that in healthy subjects. This difference may be largely due to the effect of age on apparent clearance of donepezil. Population PK analysis revealed that clearance of donepezil decreases when age increases. Compared with patients of 65-year old, younger patients of 40-year old may have a 33% increase in clearance, consistent with the observed difference in donepezil exposure between healthy younger subjects and patients who are mostly elderly people. ...Population PK analysis suggested that the clearance of donepezil in patients decreases with increase of age. Compared with patients of 65-year old, subjects of 90-year old have a 17% decrease in clearance, while patients of 40-year old have a 33% increase in clearance.
"... Population PK analysis indicated that there was a 13.5% decrease of donepezil clearance in female patients compared to male subjects.
"...Over the range of weights from 50 kg to 110 kg, clearance of donepezil increased from 7.77 L/hr to 14.04 L/hr, with a value of 10 L/hr for 70-kg individuals."

So, even if their metabolism is "normal", if your loved one is a petite, elderly female, her actual exposure to the drug is much, much higher than that of a heavy-set male with early-onset dementia.

Some experts think that the potential for serious adverse effects so far outweighs the potential for benefits, on average, that the new formulation should be pulled from the market.  See:
http://journals.lww.com/neurotodayonline/Fulltext/2011/07210/Medical_Watchdog_Groups_Asks_FDA_to_Withdraw.3.aspx
... especially the section Concern About Side Effects.


ColtsFan18
Posted: Friday, January 6, 2012 2:54 PM
Joined: 12/23/2011
Posts: 183


Even though I didn't ask I'd like to thank you Jab, my FIL was just bumped up to the 23mg dose, it's only been 2 days but I'll report any differences or side effects I may see for others to read...
Gulf Coast Gal
Posted: Saturday, January 7, 2012 3:21 PM
Joined: 12/4/2011
Posts: 39


My DH has been on the Aricept 23mg for 10 months with  very little side effects.  About the only one was the loss of 10 lbs.due to a decline in appetite the first few months he was on it, all of which he has since regained.  It may be the gender size issue for he is over 6ft and over 200 lbs.  The benefits have more than outweighed the weight issue.  A year ago when the generic form of Aricept became available our insurance company substituted it for the brand name. Within 6 weeks there was a remarkable decline in his memory.  The doctor switched him to the higher dose (he gave him a months supply to make sure he could tolerate it before we bought any) and we saw a gradual improvement to the pre-generic days.  Last summer Cerefolin was added and that has also proved beneficial.  Everyone is different, personally I think that if he is handling the 10 mg. without side effects and the Dr. wants to up it to 23 mg. it is worth the try.


ColtsFan18
Posted: Sunday, January 8, 2012 9:34 PM
Joined: 12/23/2011
Posts: 183


OK... I said I'd post any differences or effects the Ari23 had.  After 2 days (I know, I'm late posting this) as stated earlier the appetite decreased but so has the nausea.  Whether he has eaten or not, sometime between 4 and 6 in the evening he ends up throwing up.  To be safe we checked his blood pressure right after being sick and an hour later (he is on high blood pressure meds too) it was 170/110 and an hour later it was 170/100.  Pulse was between 60 and 70 bpm.  He said he felt like he had "heart flutters" but his pulse felt even.  He also said he was very cold each time just before throwing up.  I will be calling his doctor in the morning if for no other reason than to keep her apprised of the med situation, I'll follow up with what she says as soon as I speak to her.  Has anyone else had nausea after the Ari23?