Parkinson's Disease Tulip


advertisement
Reply
 
Thread Tools Display Modes
Old 03-29-2018, 02:52 PM #11
lurkingforacure lurkingforacure is offline
Senior Member
 
Join Date: Feb 2008
Posts: 1,485
15 yr Member
lurkingforacure lurkingforacure is offline
Senior Member
 
Join Date: Feb 2008
Posts: 1,485
15 yr Member
Default really can't tell:(

We are at the point to where we can't really tell if we've taken pills or not-we feel crappy most of the time. This has been going on before our Mylan generic got switched over to Sun, though. The neuro agrees we're undermedicated, and that the therapeutic dose probably needs to increase, but doesn't want to increase because that would put us at 1,000mg/day. Or more. Yikes.

Instead, he's giving us a new script for amantadine. I'm hoping it helps, because no one wants to increase sinemet if they don't absolutely have to.

You may need to shop around to find a different generic if the one you are taking isn't working/working as well as it could be.
lurkingforacure is offline   Reply With QuoteReply With Quote

advertisement
Old 03-29-2018, 04:41 PM #12
soccertese soccertese is offline
Magnate
 
Join Date: Nov 2007
Posts: 2,531
15 yr Member
soccertese soccertese is offline
Magnate
 
Join Date: Nov 2007
Posts: 2,531
15 yr Member
Default

according to this site,the mylan 50/200 shortage is over but that doesn't guarantee you can get it. it could mean that your pharmacy can get it but has a supply of the sun product they want to get rid of or their wholesaler is giving them a better price on the SUN so they're using the MYLAN shortage to use as an excuse to make a few more pennies. i'm going to reorder my mylan 50/200 tomorrow and will let you know if i can get it. this wouldn't be a problem if the FDA required that generic mfg's of extended release pills actually forced the mfg to prove their extended release capabilities matched the brand name but they don't.
FDA Drug Shortages

i didn't do well on the other indian brand mentioned, have never tried sun products. the ER versions cost around $40 for 90 tablets if you were to buy a refill privately so you have a backup supply
Carbidopa / Levodopa ER Prices and Carbidopa / Levodopa ER Coupons - GoodRx

sending you a private message
soccertese is offline   Reply With QuoteReply With Quote
Old 03-31-2018, 01:27 AM #13
johnt johnt is offline
Senior Member
 
Join Date: Apr 2009
Location: Stafford, UK
Posts: 1,059
10 yr Member
johnt johnt is offline
Senior Member
 
Join Date: Apr 2009
Location: Stafford, UK
Posts: 1,059
10 yr Member
Default

lurkingforacure writes:

"We are at the point to where we can't really tell if we've taken pills or not-we feel crappy most of the time. This has been going on before our Mylan generic got switched over to Sun, though. The neuro agrees we're undermedicated, and that the therapeutic dose probably needs to increase, but doesn't want to increase because that would put us at 1,000mg/day. Or more. Yikes."

A number of issues are raised here.

1. The maximum dose of levodopa.
See the thread "Max Sinemet Dosage????", ashleyk, June 2015
Max Sinemet Dosage???
For the reasons explained there, I see no reason for an arbitrary limit of 1000mg/day of levodopa: for some PwP it will be too much, while for others they could benefit from more.

2. The maximum dose of carbidopa.
Brod et al. write[1]:
"Recommended doses of carbidopa are 75–200 mg/day. Higher doses could inhibit brain aromatic amino acid decarboxylase and reduce clinical effects."
However, their work shows:
"Doses of 450 mg/day of carbidopa did not reduce the responses to levodopa infusion, extending the safe range of carbidopa to 450 mg/day."
So, with a normal ratio of 4:1 levodopa:carbidopa this would indicate a maximum of 1800mg/day of levodopa. An alternative option is to take some of the levodopa dose in the 10:1 formulation.

3. The efficacy of generics.
Generics must satisfy bioequivalence rules. These are based on the pharmacokinetic parameters CMAX (maximum concentration) and AUC (area under the curve) [2]:
"The FDA considers two products bioequivalent if the 90% CI of the relative mean Cmax, AUC(0–t) and AUC(0–∞) of the test (e.g. generic formulation) to reference (e.g. innovator brand formulation) should be within 80% to 125% in the fasting state."
This is complicated. It is couched in probabalistic terms. I make a very rough estimate that this means that it is OK, as far as the regulators are concerned, for variations of up to 5% by weight of the active component to be acceptable. This variation is noticeable by PwP. They would notice that they went "off" sooner than usual or that they never crossed the "on" threshold.

References

[1] "Are high doses of carbidopa a concern? A randomized clinical trial in Parkinson’s disease"
Lissa S. Brod, MD,1,2 Jason L. Aldred, MD,1,2 and John G. Nutt, MD1,
Mov Disord, Apr 2012
Are high doses of carbidopa a concern? A randomized clinical trial in Parkinson’s disease

[2] Bioequivalence - Wikipedia

John
__________________
Born 1955. Diagnosed PD 2005.
Meds 2010-Nov 2016: Stalevo(75 mg) x 4, ropinirole xl 16 mg, rasagiline 1 mg
Current meds: Stalevo(75 mg) x 5, ropinirole xl 8 mg, rasagiline 1 mg

Last edited by johnt; 03-31-2018 at 01:34 AM. Reason: clarity
johnt is offline   Reply With QuoteReply With Quote
"Thanks for this!" says:
jeffreyn (03-31-2018), kiwi33 (03-31-2018), lurkingforacure (03-31-2018)
Old 03-31-2018, 09:28 AM #14
soccertese soccertese is offline
Magnate
 
Join Date: Nov 2007
Posts: 2,531
15 yr Member
soccertese soccertese is offline
Magnate
 
Join Date: Nov 2007
Posts: 2,531
15 yr Member
Default

Quote:
Originally Posted by johnt View Post
lurkingforacure writes:

"We are at the point to where we can't really tell if we've taken pills or not-we feel crappy most of the time. This has been going on before our Mylan generic got switched over to Sun, though. The neuro agrees we're undermedicated, and that the therapeutic dose probably needs to increase, but doesn't want to increase because that would put us at 1,000mg/day. Or more. Yikes."

A number of issues are raised here.

1. The maximum dose of levodopa.
See the thread "Max Sinemet Dosage????", ashleyk, June 2015
Max Sinemet Dosage???
For the reasons explained there, I see no reason for an arbitrary limit of 1000mg/day of levodopa: for some PwP it will be too much, while for others they could benefit from more.

2. The maximum dose of carbidopa.
Brod et al. write[1]:
"Recommended doses of carbidopa are 75–200 mg/day. Higher doses could inhibit brain aromatic amino acid decarboxylase and reduce clinical effects."
However, their work shows:
"Doses of 450 mg/day of carbidopa did not reduce the responses to levodopa infusion, extending the safe range of carbidopa to 450 mg/day."
So, with a normal ratio of 4:1 levodopa:carbidopa this would indicate a maximum of 1800mg/day of levodopa. An alternative option is to take some of the levodopa dose in the 10:1 formulation.

3. The efficacy of generics.
Generics must satisfy bioequivalence rules. These are based on the pharmacokinetic parameters CMAX (maximum concentration) and AUC (area under the curve) [2]:
"The FDA considers two products bioequivalent if the 90% CI of the relative mean Cmax, AUC(0–t) and AUC(0–∞) of the test (e.g. generic formulation) to reference (e.g. innovator brand formulation) should be within 80% to 125% in the fasting state."
This is complicated. It is couched in probabalistic terms. I make a very rough estimate that this means that it is OK, as far as the regulators are concerned, for variations of up to 5% by weight of the active component to be acceptable. This variation is noticeable by PwP. They would notice that they went "off" sooner than usual or that they never crossed the "on" threshold.

References

[1] "Are high doses of carbidopa a concern? A randomized clinical trial in Parkinson’s disease"
Lissa S. Brod, MD,1,2 Jason L. Aldred, MD,1,2 and John G. Nutt, MD1,
Mov Disord, Apr 2012
Are high doses of carbidopa a concern? A randomized clinical trial in Parkinson’s disease

[2] Bioequivalence - Wikipedia

John
JOHN, i haven't looked at this for awhile but generic mfgs don't have to test their drugs on pd'ers, i believe they test only on non-pd'ers' for blood levels. i can understand the reasoning there. and up until recently there has been no testing required for a generic ER (extended release) version to have a similar drug release pattern, i.e., in a healthy patient, what is the half-life and they don't have to prove that it's as long as the brand name. you can assume that the generic mfg would want to be close to the brand name's ER characteristics but i doubt there are that many patients taking brand name sinemet to notice a difference because insurance companies won't readily pay the higher cost. and to totally upset the apple cart, the original mfg of sinemet is squibb who prior to 2012 paid MERCK to make sinemet and MERCK contracts with mylan to make the drug, check the SINEMET insert, there's a picture of the tiny picture on every SINEMET label saying MFG'ED BY MYLAN. So in this case, i'm not sure what numbers the FDA uses to determine if a new generic sinemet's l-dopa peak concentration is ok, i assume MERCK, since i assume that the generic testing involves testing the current brand name, not just using +30 year old numbers from squibb. i'm not criticizing the MYLAN brand, i like it. i liked teva better but they sold off their generic rights along with their rights to the ACTAVIS brand to MAYNE when they bought ALLERGAN which ownd the indian mfg ACTAVIS. The end result is no more TEVA c/l and MAYNE is now selling the C/L made by ACTAVIS and possibly SUN is selling the ACTAVIS manufactured product?

i've noticed differences with some generics, primarily i just feel sick when taking it and/or less relief, i blame feeling sick on dyes, fillers and possible contaminants plus the extra stuff they add to the ER variations to slowly break down and release little chunks of tablet which extends it's lifetime. i assume the reason C/L ER releases C/L for a longer time period than the IR C/L is for that reason, the longer it is protected from enzymes in the stomach breaking down the l-dopa, the greater chance of more l-dopa getting to the small intestine where it is absorbed. that's why you want to slow your stomach emptying a little when taking C/R, if you speed up emptying by taking CR on an empty stomach more of it will leave the stomach still in the pill form which will pass right by the area of the small intestine where it is absorbed. i have to admit i've never found information on the internet describing exactly how CR C/L works to slow release but my guess sounds pretty good?

this is a complicated subject and i'm no expert. all i can say is try to have a 30 day backup supply, more if possible, of your C/L regardless of whether you think one generic is better than another. disruptions in supply chains are going to become more common with global warming and more raw ingredients bought from other countries, especially china and india and more mfg'i
ng occurring in lesser developed countries. there's just a greater chance of a plant being damaged like what happened to mylan in puerto rico, where the mfg and wholesalers didn't have enough inventory to keep supplying the drug or god forbid, trump puts a tariff on some ingredients used in manufacturing ER (cr) C/L, maybe some rare wax, or a bad batch of drug is manufactured for a myriad of reasons. and manufacturers can make a bad batch of drugs, doesn't happen often so good to have some pills from an older batch to compare against. this ain't no trivial matter, a small difference in strength or with the CR/ER versions poor quality or just more of the addons to make the pill dissolve slowly MIGHT make that generic intolerable imho. i kind of feel like i might be unusually sensitive to differences and my neuro doesn't believe there are major differences so i may just be creating a false alarm. fwiw, here's an interesting marketing paper from merck, i think 2011 date, where they make the argument that name brand is better!! is it just patient perception? i forgot to point out that even though MYLAN mfg's SINEMET for MERCK, the mylan and MERCK tablets aren't absolutely identical,the mylan is scored, the brand name isn't. and i don't know if the formulas are the same.
Parkinson drug sinemet-LIFE CYCLE STRATEGIC PLAN

"A problem in manufacturing change from Merck to Mylan in 2010 lead to worldwide shortage.  Despite the differences of Mylan Sinemet from Merck Sinemet, it is still more effective than generic formulations"


this is in the presentation:

Non-medicinal ingredients • Crospovidone, hydroxypropylcellulose, magnesium stearate, microcrystalline cellulose, pregelatinized starch Storage and stability • Store your tablets at room temperature (15°C–30°C). Store in tightly closed container, protected from light and moisture.

this presentation is very interesting if you want more info on CL in general, it's history and how it works. best quick read i've seen.
soccertese is offline   Reply With QuoteReply With Quote
"Thanks for this!" says:
jeffreyn (03-31-2018)
Reply

Tags
mylan, pharmaceuticals, read, sinemet, sun

Thread Tools
Display Modes

Posting Rules
You may not post new threads
You may not post replies
You may not post attachments
You may not edit your posts

BB code is On
Smilies are On
[IMG] code is On
HTML code is Off


Similar Threads
Thread Thread Starter Forum Replies Last Post
Aquinnah Pharmaceuticals recibe financiación de Takeda Pharmaceuticals para nuevas te MuonOne ALS News & Research 0 12-22-2015 09:28 AM


All times are GMT -5. The time now is 12:21 PM.

Powered by vBulletin • Copyright ©2000 - 2024, Jelsoft Enterprises Ltd.

vBulletin Optimisation provided by vB Optimise v2.7.1 (Lite) - vBulletin Mods & Addons Copyright © 2024 DragonByte Technologies Ltd.
 

NeuroTalk Forums

Helping support those with neurological and related conditions.

 

The material on this site is for informational purposes only,
and is not a substitute for medical advice, diagnosis or treatment
provided by a qualified health care provider.


Always consult your doctor before trying anything you read here.