Can't dry cut no more need some advice. Builder?

[[Ma...]]

This is from the FDA website:

 

An ANDA must show the generic medicine is equivalent to the brand in the following ways:

 

The active ingredient is the same as that of the brand-name drug/innovator drug.

An active ingredient in a medicine is the component that makes it pharmaceutically active — effective against the illness or condition it is treating.

Generic drug companies must provide evidence that shows that their active ingredient is the same as that of the brand-name medicine they copy, and FDA must review that evidence.

 

The generic medicine is the same strength.

[[bu...]]

 

 

Builder, where did you find this info about +/- variation of 15% in ingredient content? What I read is that there can be 0 variation in ingredient content. What can vary  by 5-10% is the blood concentration after taking the pill, which of course depends on the fillers, etc. and absorption characteristics of the pill. Also, I don't think there is much variability in distribution in the pills. Pharma companies have pretty good mixers.

 

"...the requirements for dose uniformity are met if the amount of the active ingredient in 10 dosage units as determined from the weight variation and content uniformity method  lies within the range of 85.0% and 115.0% of the label claim..."

 

http://www.pharmacopeia.cn/v29240/usp29nf24s0_c905.html

\

 

This is a Chinese website. I wouldn't take it too seriously.

 

The same info is available on dozens of websites.  That's just the first one I pulled up today.

[[bu...]]

This is from the FDA website:

 

An ANDA must show the generic medicine is equivalent to the brand in the following ways:

 

The active ingredient is the same as that of the brand-name drug/innovator drug.

An active ingredient in a medicine is the component that makes it pharmaceutically active — effective against the illness or condition it is treating.

Generic drug companies must provide evidence that shows that their active ingredient is the same as that of the brand-name medicine they copy, and FDA must review that evidence.

 

The generic medicine is the same strength.

 

...which says absolutely nothing about dose or weight variability tolerances.

[[Ma...]]

The generics have to have the number of milligrams of drug that is included on the label in the pills. You can take it to the bank that that does not vary. In addition, the pill needs to get you within 10 percent above or below the blood concentrations achieved with the brand for the FDA to approve the generic, and in reality, they only usually vary by 3-4 percent in one direction or another. So yes, they are very similar in terms of the active ingredient. It is possible that one generic will get you a 3 percent lower concentration than the brand and another can get you a concentration that is 3 percent above the brand and therefore the two generics can be 6% different from each other. Most people will never notice a difference.

 

https://www.huffingtonpost.com/2015/02/22/generic-prescriptions_n_6730194.html

 

[[bu...]]

 

 

Builder, where did you find this info about +/- variation of 15% in ingredient content? What I read is that there can be 0 variation in ingredient content. What can vary  by 5-10% is the blood concentration after taking the pill, which of course depends on the fillers, etc. and absorption characteristics of the pill. Also, I don't think there is much variability in distribution in the pills. Pharma companies have pretty good mixers.

 

"...the requirements for dose uniformity are met if the amount of the active ingredient in 10 dosage units as determined from the weight variation and content uniformity method  lies within the range of 85.0% and 115.0% of the label claim..."

 

http://www.pharmacopeia.cn/v29240/usp29nf24s0_c905.html

 

This is a Chinese website. I wouldn't take it too seriously.

 

Its simply a copy of section 905 of United States Pharmacopeia.  You can find it on any number of academic, medical, and pharmaceutical web pages.

 

https://www.usp.org/sites/default/files/usp/document/harmonization/gen-method/q0304_pf_ira_32_6_2006.pdf

 

https://www.usp.org/sites/default/files/usp/document/harmonization/gen-method/q0304_pf_30_4_2004.pdf

 

https://www.arlok.com/sites/default/files/2018-03/Quality-Control%20Analytical%20Methods%20-%20Homogeneity%20of%20Dosing%20Forms_0.pdf

 

[[Ma...]]

Unfortunately, the first two links are incomplete, as they do not mention what they refer to. The third one talks about rules for compounding pharmacies. It would be really nice to know what are the rules.

[[bu...]]

Unfortunately, the first two links are incomplete, as they do not mention what they refer to. The third one talks about rules for compounding pharmacies. It would be really nice to know what are the rules.

 

Strange, they all work for me. 

 

But if you can open the last one, just look at the first page, and you will find this (as a flow chart):

 

Step 1:

Test 10 unit doses

All 10 unit doses (between)

  85% and  115%

if yes

ACCEPT

 

 

And if you read on down, you will find there is even an exception that actually allows 1 sample in to fail, and still pass the lot.

[[Ma...]]

Builder, the way I see it link 3 refers to Compounding Pharmacies and not Generic Manufacturers. The rules may or may not be the same for the two.

[[bu...]]

From my 2nd link, starting on p.7  and continuing on p.8...

 

"The requirements for dosage uniformity are met if the amount of the drug substance in each of the 10 dosage units as determined from the Content Uniformity method lies within the range of 85.0% to 115.0% of the label claim,... (emphasis added)

And it goes on to detail the follow-up procedure if 1 or the 10 fail even that loose  criteria.

 

This has been the  United States Pharmacopeia Standard for many years, and you will note that my last link is a 2018 publication.  This exact language can be found in each of the 4 links I posted,  (and dozens of others) if you search.

[[Ho...]]

Builder is correct with his references, although they are a little outdated. The USP is up to version 41 now. 

 

20 tablets tested together (all 20 tablets put into one bottle) must be 90-110% of the label claim. Tablets tested individually can be 85-115% of the label claim.

 

Yes, generics must match blood levels of the brand name they are the generic of. But "match" when used for testing such small amounts in the blood means the test results can vary quite a bit, not only because of differences in people, but because it is very imprecise when measuring such small quantities.

[[bu...]]

Builder is correct with his references, although they are a little outdated. The USP is up to version 41 now. 

 

20 tablets tested together (all 20 tablets put into one bottle) must be 90-110% of the label claim. Tablets tested individually can be 85-115% of the label claim.

 

Yes, generics must match blood levels of the brand name they are the generic of. But "match" when used for testing such small amounts in the blood means the test results can vary quite a bit, not only because of differences in people, but because it is very imprecise when measuring such small quantities.

 

[[Ma...]]

Builder is correct with his references, although they are a little outdated. The USP is up to version 41 now. 

 

20 tablets tested together (all 20 tablets put into one bottle) must be 90-110% of the label claim. Tablets tested individually can be 85-115% of the label claim.

 

Yes, generics must match blood levels of the brand name they are the generic of. But "match" when used for testing such small amounts in the blood means the test results can vary quite a bit, not only because of differences in people, but because it is very imprecise when measuring such small quantities.

 

Thank you.

[[in...]]

Hi, I dry cut down to 0.05mg Ativan using a balance like yours. I crushed the pills into powder, store it in a closed plastic container and took the amount I needed everyday.

 

This method works very well

 

Hi Magnesi. Or Anyone dry cutting skills.

 

I'm trying to cut my last 4mg valium. 2, 2mg pills. Having trouble with liquid tapering. Where do I find the basics and direction for dry cutting, crushing pills, how, how to measure out please? I see the Gemini scale is suggested by a couple persons.

 

Thanks in advance

Infoshare.

[[ma...]]

Hi infoshar, I also used the Gemini scale, plus something like this to crush the tablets https://www.amazon.com/dp/B07B8QHG63/ref=sspa_dk_detail_3?psc=1&pd_rd_i=B07B8QHG63&pd_rd_wg=inOX2&pd_rd_r=7JJGP67R9J72FZMG89EC&pd_rd_w=gGEYl. I stored the powder in the pill crusher itself and used a small spoon I made from aluminum foil to pick the powder. After practicing a little it becomes easy.

Feel free to ask for further details.

[[in...]]

Thanks Magnesi,

 

Are there instructions anywhere on this board on the basics, how much to remove each day etc?

Ativan is a difficult one to cut directly from. Congrats on you taper.

 

I had become pretty good at the LDMT maths and measurements. I guess it will take some new practice.

 

Infoshare.

[[Ji...]]

Hi infoshar

 

Have a look here: http://benzo.alwaysdata.net/ . Don't forget to visit the HELP section first.

 

All the best.

[[ma...]]

Thanks Magnesi,

 

Are there instructions anywhere on this board on the basics, how much to remove each day etc?

Ativan is a difficult one to cut directly from. Congrats on you taper.

 

I had become pretty good at the LDMT maths and measurements. I guess it will take some new practice.

 

Infoshare.

 

You're welcome infoshar. Regarding the tapering rate, I cut at aprox 1% per day and held the dose whenever I started feeling bad until I felt OK again. 1% per day corresponds more or less to the fastest recommended rate of 10% every 10 days. My holding periods lasted from one week to three months and I estimate that, overall, they represent nearly half of the taper.

 

You can see the whole taper on this graph https://docs.google.com/spreadsheets/d/e/2PACX-1vT0DJKwCV4UB8-ZbQfpo1wleTKp8H6SPi_IKsW7XX2BbJ8C2FYyTpD-nFAUr-O1pM6OEDE9uvUu7Ba4/pubchart?oid=1900834401&format=interactive.

 

[[in...]]

Hi Jim

I'm wondering if your poll of liquid tapering folks ....did most of them updose first or not? Would updosing make a difference?

Or is liquid just not gonna metabolize well in me for diazapam ldmt? Vodka lmdt worked for me for lose dose mirtazapine taper perfectly.

 

Thanks

Infoshare

[[Ji...]]

Hi infoshar

 

I'm wondering if your poll of liquid tapering folks ....did most of them updose first or not? Would updosing make a difference?

These two questions were not part of the poll

 

I have read a number of posts about the intriguing updose question. It appears that in only very few cases updoses can bring benefits. It's when your updose occurs within one or two weeks max from the last dose change. It varies from individuals but it rarely gives good results when one month or more have passed since the last cut. In those cases, by updosing taperer believes he will obtain the same stability before the cut. Nothing like that will happen as his CNS has undergone for one month the lower drug conditions, has adjusted to it more or less successfully and now the equilibrium has definitely shifted. Not only the updose does not relieve the withdrawal symptoms but for some people, it seems that going back on their previous dose too late can actually make symptoms worse.

 

What to do then? Usually they hold until the storm passes and the CNS catches up with the cut. Then they resume the taper.

 

Or is liquid just not gonna metabolize well in me for diazapam ldmt? Vodka lmdt worked for me for lose dose mirtazapine taper perfectly.

There's a category of taperers that simply could not tolerate liquid, whatever it is and however small the swallowed quantity can be. For those a Direct Taper by using dry tablets previously reduced to powder resulted more suitable with clearly less symptoms.

[[in...]]

Thanks Jim..

I'm still wondering whether up dosing before you take a cut of the liquid version say up dosing 10% or so would prevent those difficulties of liquid tapering that some of us are having

Thanks  infoshare

[[Ji...]]

Hi infoshar

 

From BB posts I've read in a specific thread that started years ago, I happened to see the word "bioavailability" for the first time. With this term, people were explaining why benzo  swallowed as liquid seems to loose effects compared to when taken as tablet. Without going into details, I remember some knowledgeable buddies in there estimated the diminution to about 5-10%. They also recommended to updose accordingly to prevent withdrawal symptoms following the switch from tablet to liquid.

 

Later on, I happened to read a number of other buddies encountered the same problem when switching to liquid. Contrarily to the above cases, they just found the effect diminution is much more important than 5-10%. Some of them have actually likened the drop to an abrupt discontinuation.

 

Have you ever wondered what if you updose say 10% and instead of stability you just feel same symptoms because you belong to the second group? Are you going to try 20%, 40%, 50% ...until you feel stable knowing that every change in dose requires some time to get stabilized in your bloodstream? In my opinion, it could be a long and difficult search coping with an ever changing CNS that eludes you by continuously readjusting itself, at its own pace, to the new doses.

 

This is why I believe in the hold solution with a defined dose and amid symptoms give your CNS enough time to slowly readjust to the reduction of the drug it had previously grown acclimated to. Then resume taper, slower and gentler.

[[in...]]

Thanks Jim

In your answer you talk about the hold solution are you referring to cut and hold or to any method and hold I mean obviously one would hold until their stabilize I would think.

 

I'm just wondering whether I missed the step of up dosing 10% before I started the liquid I just crossed over in my recent attempts to to liquid and just held for several days to a week and it did feel like an almost cold Turkey I didn't even take a cut so does that mean even if I up dosed 10% before I held I would still have the same band effect? I suppose.

 

Well then I need measurenent numbers for gram scale cutting. Ive searched many times and have asked but nithing yet. I had great luck with vidka mucro taper of mirt with a rounded up dose at beginning. So Im trying to figure why diazapam is so diff from mirt. Thanks.

 

Infoshare