Generic substitution

[nikei3ball]

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I have a question about substitution of Levoxyl (King Pharmaceuticals) for a generic. I looked up in the Orange Book for AB equivalence. Under TE code it says AB1, AB3. Then I searched for levothyroxine. Do the generics have to have both AB1 & AB3 or just one of them to be able to be substituted? i.e. one by Genpharm says AB2, AB3...is this acceptable??

 

[Priapism321]

I have a question about substitution of Levoxyl (King Pharmaceuticals) for a generic. I looked up in the Orange Book for AB equivalence. Under TE code it says AB1, AB3. Then I searched for levothyroxine. Do the generics have to have both AB1 & AB3 or just one of them to be able to be substituted? i.e. one by Genpharm says AB2, AB3...is this acceptable??

Looks like only one common TE code is required; I come to that conclusion after perusing this.

From here: http://www.fda.gov/cder/ob/docs/preface/ecpreface.htm#1.8 Description of Special Situations


"Levothyroxine Sodium. Because there are multiple reference listed drugs of levothyroxine sodium tablets and some reference listed drugs' sponsors have conducted studies to establish their drugs' therapeutic equivalence to other reference listed drugs, FDA has determined that its usual practice of assigning two or three character TE codes may be potentially confusing and inadequate for these drug products. Accordingly, FDA provides the following explanation and chart of therapeutic equivalence evaluations for levothyroxine sodium drug products.

Levothyroxine Sodium (Mylan ANDA 76187), tablets have been determined to be therapeutically equivalent to corresponding strengths of Unithroid (Jerome Stevens NDA 021210) tablets.

Levo-T (Alara NDA 021342), Levothyroxine Sodium (Mylan ANDA 76187), Unithroid (Jerome Stevens NDA 021210) and Levothyroxine Sodium (Genpharm ANDA 76752)tablets have been determined to be therapeutically equivalent to corresponding strengths of Synthroid (Abbott NDA 021402) tablets.

Levo-T (Alara NDA 021342), Unithroid (Jerome Stevens NDA 021210), Levothyroxine Sodium (Mylan ANDA 076187) and Levothyroxine Sodium (Genpharm ANDA 76752) tablets have been determined to be therapeutically equivalent to corresponding strengths of Levoxyl (King Pharms NDA 021301) tablets.

Levothyroxine Sodium (Mylan ANDA 76187) tablets have been determined to be therapeutically equivalent to corresponding strengths of Levothroid (Lloyd NDA 021116) tablets.

Levothroid (Lloyd NDA 021116) requires further investigation and review to establish therapeutic equivalence to corresponding strengths of any other levothyroxine sodium drug products and is rated BX.

The chart outlines TE codes for all 0.025mg products with other products being similar. Therapeutic equivalence has been established between products that have the same AB+number TE code. More than one TE code may apply to some products. One common TE code indicates therapeutic equivalence between products."

 

[UTPharm]

i thought u werent really supposed to be changing around pts brand of thyroid medication?

 

[Priapism321]

i thought u werent really supposed to be changing around pts brand of thyroid medication?

Oh yeah, why? An acceptable answer will only be accompanied by a well designed scientific evaluation substantiating such a "thought." Unfortunately, I already know that such a thing does not exist, but I will give you a shot. A completely unacceptable answer will be stating what you "have heard" or "have read in the news." Go.

 

[monsterbrain]

Oh yeah, why? An acceptable answer will only be accompanied by a well designed scientific evaluation substantiating such a "thought." Unfortunately, I already know that such a thing does not exist, but I will give you a shot. A completely unacceptable answer will be stating what you "have heard" or "have read in the news." Go.

Geez! I don't think UTPharm was attacking your information. I read it as "this is what my current knowledge has led me to believe, but help me to understand why switching meds won't create any problems."

I read your response as "I'm a pompous a**." Sorry, but your response to UTPharm was just as harsh.

 

[UTPharm]

I learned from personal experience when a pt came into the pharmacy i worked at and asked what his medication was, and it was a generic levo, not synthroid. I told him that it was the generic for synthroid, and it was probably ok, but the a senior intern overheard and stepped in and told me that it isnt good to substitute or change brands around, and this also holds true for anticonvulsants. i remember it being mentioned in class, also, i will try and find my pharmacology notes to further explain.

Oh yeah, why? An acceptable answer will only be accompanied by a well designed scientific evaluation substantiating such a "thought." Unfortunately, I already know that such a thing does not exist, but I will give you a shot. A completely unacceptable answer will be stating what you "have heard" or "have read in the news." Go.

 

[UTPharm]

Thyroid.org and the FDA good enough for you?



"The current recommendation by the FDA and these organizations is that patients switching between branded levothyroxine products have repeat thyroid function testing, which will allow for dose retitration if the therapeutic target is not being achieved with the new preparation. “Under a policy of allowing generic levothyroxine substitution,” the statement concludes, “more frequent thyroid function testing will be necessary.” Furthermore, the statement cautions, the patient and doctor may not be aware of a change in preparation before adverse events occur.
As a result of the FDA decision, the ATA, TES, and AACE advise physicians caring for patients on levothyroxine therapy to —
1. Alert their patients that their levothyroxine preparation may be switched at the pharmacy,
2. Encourage their patients to ask to remain on their current levothyroxine preparation, and
3. Make sure their patients understand that if they receive a new levothyroxine preparation that they will need to be retested with a serum TSH to determine if they need dose retitration."



http://www.thyroid.org/professionals/advocacy/04_06_24_fda.html

 

[brose]

I have a question about substitution of Levoxyl (King Pharmaceuticals) for a generic. I looked up in the Orange Book for AB equivalence. Under TE code it says AB1, AB3. Then I searched for levothyroxine. Do the generics have to have both AB1 & AB3 or just one of them to be able to be substituted? i.e. one by Genpharm says AB2, AB3...is this acceptable??

First of all, you can legally substitute an AB1 for an AB1, or and AB2 for an AB2, but not an AB3 for an AB2. If a drug has both AB1 and AB2 codes, it can be substituted for a reference drug that is either AB1 or AB2.

Second, as far as substitution of levothyroxine or anticonvulsants it is not illegal per Federal Law; however, some states do have laws limiting their substituion. These drugs are known as Narrow Therapeutic index drugs, meaning the difference between subtherapeutic doses and toxic doses is very small. Essentially, these are drugs that need to be closely monitored as the slightest change can result in large changes physiologically (e.g. warfarin influencing INR).

As we all know, or will learn, for a drug product to be considered "bioequivalent" it must be the same chemical compound and must meet certain ADME criteria. For drugs to meet those standards of bioequivalence, they need only be within a certain % of say AUC (15% I think), Cmax, and Tmax. For most drugs, a 15% difference in AUC will not make a big enough difference therapeutically, and can be substituted without worry. However, a 15% difference in AUC for say warfarin or levothyroxin can have a potentially major influence over INR or TSH respectively. Hense the reason that changing from Synthroid to levo, Coumadin to warfarin, or Dilantin to phenytoin is not a good practice; even where it is legal.

Hopefully this response will answer some of your questions.

 

[Priapism321]

Thyroid.org and the FDA good enough for you?

Actually, no. I asked for scientific evidence concluding that switching preparations of levothyroxine causes some sort of harm.

 

[Priapism321]

And, before I could ever take a press release from the ATA seriously, you will have to tell me how much money they receive from Abbott Laboratories each year (not to mention you linked a press release from 4 years ago). I can tell you that their friends over at the AACE (American Association of Clinical Endocrinologists) took 7 figures from Abbott in 2006 or 2007.

 

[UTPharm]

After this post i'm done with this topic.

In our pharmacology notes it mentions a "brand generic controversy" and pts must be retested if their medication is changed to make sure it is effective. Is it going to hurt the pt if you change their medication? Probably not. but why suggest them to the hassles that are recommended?

And, before I could ever take a press release from the ATA seriously, you will have to tell me how much money they receive from Abbott Laboratories each year (not to mention you linked a press release from 4 years ago). I can tell you that their friends over at the AACE (American Association of Clinical Endocrinologists) took 7 figures from Abbott in 2006 or 2007.

 

[UTPharm]

Thanks for your reply. cleared it up even more for me.

First of all, you can legally substitute an AB1 for an AB1, or and AB2 for an AB2, but not an AB3 for an AB2. If a drug has both AB1 and AB2 codes, it can be substituted for a reference drug that is either AB1 or AB2.

Second, as far as substitution of levothyroxine or anticonvulsants it is not illegal per Federal Law; however, some states do have laws limiting their substituion. These drugs are known as Narrow Therapeutic index drugs, meaning the difference between subtherapeutic doses and toxic doses is very small. Essentially, these are drugs that need to be closely monitored as the slightest change can result in large changes physiologically (e.g. warfarin influencing INR).

As we all know, or will learn, for a drug product to be considered "bioequivalent" it must be the same chemical compound and must meet certain ADME criteria. For drugs to meet those standards of bioequivalence, they need only be within a certain % of say AUC (15% I think), Cmax, and Tmax. For most drugs, a 15% difference in AUC will not make a big enough difference therapeutically, and can be substituted without worry. However, a 15% difference in AUC for say warfarin or levothyroxin can have a potentially major influence over INR or TSH respectively. Hense the reason that changing from Synthroid to levo, Coumadin to warfarin, or Dilantin to phenytoin is not a good practice; even where it is legal.

Hopefully this response will answer some of your questions.

 

[Priapism321]

After this post i'm done with this topic.

In our pharmacology notes it mentions a "brand generic controversy" and pts must be retested if their medication is changed to make sure it is effective. Is it going to hurt the pt if you change their medication? Probably not. but why suggest them to the hassles that are recommended?

We can, and should be done with this topic; at this point I have a headache. But, I must point out that your pharmacology notes are the furthest thing from substantial scientific evidence to substantiate anything that has been asserted to this point. It would be hard to get any further.

 

[Priapism321]

As we all know, or will learn, for a drug product to be considered "bioequivalent" it must be the same chemical compound and must meet certain ADME criteria. For drugs to meet those standards of bioequivalence, they need only be within a certain % of say AUC (15% I think), Cmax, and Tmax. For most drugs, a 15% difference in AUC will not make a big enough difference therapeutically, and can be substituted without worry. However, a 15% difference in AUC for say warfarin or levothyroxin can have a potentially major influence over INR or TSH respectively. Hense the reason that changing from Synthroid to levo, Coumadin to warfarin, or Dilantin to phenytoin is not a good practice; even where it is legal.

This number is closer to say 2 or 3% for most drugs when you actually look at the raw data, and the standards for bioequivalence are set so that generic product parameters can vary about as much as a brand name product's lot to lot variability (ie, the difference between Lot A of Synthroid and Lot A of generic levothyroxine is the same as the difference between Lot A of Synthroid and Lot B of Synthroid). This is simply fact.

If the FDA's standards are potentially harmful to the public, they should change them, right? If you think the rules are too loose, I would start a petition in the name of your patients.

 

[SpirivaSunrise]

And, before I could ever take a press release from the ATA seriously, you will have to tell me how much money they receive from Abbott Laboratories each year (not to mention you linked a press release from 4 years ago). I can tell you that their friends over at the AACE (American Association of Clinical Endocrinologists) took 7 figures from Abbott in 2006 or 2007.

Oh Pri, how I pity the poor students who'll get you as a preceptor one day!

Funny you bring up AACE; I remember getting a kick out of their press release I came across a few months ago when FL pulled levo off of the negative formulary. Can't find it now...but it was quite amusing.

 

[Priapism321]

Oh Pri, how I pity the poor students who'll get you as a preceptor one day!

Funny you bring up AACE; I remember getting a kick out of their press release I came across a few months ago when FL pulled levo off of the negative formulary. Can't find it now...but it was quite amusing.

Oh, they put out a public service announcement on florida radio stations. This is what prompted me to search their records to see who they may be beholden to. I was not surprised at what I discovered to say the least.

I will link the page for you, though I am risking the children listening in and believing this stuff.

http://www.aace.com/pub/positionstatements/floridaruling.php

 

[SpirivaSunrise]

Oh, they put out a public service announcement on florida radio stations. This is what prompted me to search their records to see who they may be beholden to. I was not surprised at what I discovered to say the least.

I will link the page for you, though I am risking the children listening in and believing this stuff.

http://www.aace.com/pub/positionstatements/floridaruling.php

Ha! That's it.

Lol...seriously? They had radio announcements? Fantastic. 🙄

Gutsy call by the judge who made the ruling though don't ya think? I haven't seen many that will step in on board of pharmacy/medicine's turf.

 

[brose]

This number is closer to say 2 or 3% for most drugs when you actually look at the raw data, and the standards for bioequivalence are set so that generic product parameters can vary about as much as a brand name product's lot to lot variability (ie, the difference between Lot A of Synthroid and Lot A of generic levothyroxine is the same as the difference between Lot A of Synthroid and Lot B of Synthroid). This is simply fact.

If the FDA's standards are potentially harmful to the public, they should change them, right? If you think the rules are too loose, I would start a petition in the name of your patients.

My statement was concerning what the allowable variance was to be considered bioequavalent, not the true raw data. For that reason, and that reason alone, is it considered by the FDA to be a poor practice and by some states to be against the law.

I don't believe I ever stated that the rules were "too loose" or that they were "dangerous to patients", if I did please point that out to me. I was simply explaining the logic (or lack thereof in your opinion) of several states laws concerning this issue, what is lectured upon in class to the students who visit this board, and what the FDA believes to be "good practice". As far as I am aware, there is no concrete scientific evidence to back up this claim; these recommendations are in place due to case reports of varying TSH in patients who switch from one mfg. to another and the hypothetical scenario that could allow for differing pharmacodynamics. And as with the vast majority of pharmacological issues, it is a risk vs. benefit scenario and if one feels that the risk of switching back and forth from one mfg. to another is greater than the benefit of the price reduction then what is the point? In most states it is considered to be "professional judgement" that rules on this issue, while other states it is a legal issue. I don't really think it is fair to these students to stress your own professional judgement over others, especially if they have not had the time or experience to decide for themselves. The books teach it, the FDA recommends it, some states mandate it. That in itself is enough for me to at least make my patients aware of the possibility and let them decide for themselves.

I hope you understand I did not set out to argue with you Priapism, I was simply hoping to clear the muddy waters for these students. They weren't taught "wrong" in school, you are not wrong for your statements, its all a matter of judgement.

 

[PharmDstudent]

Geez! I don't think UTPharm was attacking your information. I read it as "this is what my current knowledge has led me to believe, but help me to understand why switching meds won't create any problems."

I read your response as "I'm a pompous a**." Sorry, but your response to UTPharm was just as harsh.

You'll have to forgive Priapism321. He's had an erection lasting longer than 4 hours since April of '07. 🙁

 

[monsterbrain]

You'll have to forgive Priapism321. He's had an erection lasting longer than 4 hours since April of '07. 🙁

 

[Twins fan]

You'll have to forgive Priapism321. He's had an erection lasting longer than 4 hours since April of '07. 🙁

That's funny right there

 

[Twins fan]

My statement was concerning what the allowable variance was to be considered bioequavalent, not the true raw data. For that reason, and that reason alone, is it considered by the FDA to be a poor practice and by some states to be against the law.

I don't believe I ever stated that the rules were "too loose" or that they were "dangerous to patients", if I did please point that out to me. I was simply explaining the logic (or lack thereof in your opinion) of several states laws concerning this issue, what is lectured upon in class to the students who visit this board, and what the FDA believes to be "good practice". As far as I am aware, there is no concrete scientific evidence to back up this claim; these recommendations are in place due to case reports of varying TSH in patients who switch from one mfg. to another and the hypothetical scenario that could allow for differing pharmacodynamics. And as with the vast majority of pharmacological issues, it is a risk vs. benefit scenario and if one feels that the risk of switching back and forth from one mfg. to another is greater than the benefit of the price reduction then what is the point? In most states it is considered to be "professional judgement" that rules on this issue, while other states it is a legal issue. I don't really think it is fair to these students to stress your own professional judgement over others, especially if they have not had the time or experience to decide for themselves. The books teach it, the FDA recommends it, some states mandate it. That in itself is enough for me to at least make my patients aware of the possibility and let them decide for themselves.

I hope you understand I did not set out to argue with you Priapism, I was simply hoping to clear the muddy waters for these students. They weren't taught "wrong" in school, you are not wrong for your statements, its all a matter of judgement.

Thank you brose for your input on this topic. You did help clear up some confusion for me. I have heard the same thing as UTPharm while working in a pharmacy, and was puzzled by Priapism's snottiness in his comments relating to the topic, as if all pharmicists and doctors that have counseled patients to be careful when switching brands of levothyroxine just said "f it, this is what I'll tell 'em."

 

[UTPharm]

its because he is a resident. wouldnt be the first one ive met that thinks they know it all 🙂

Thank you brose for your input on this topic. You did help clear up some confusion for me. I have heard the same thing as UTPharm while working in a pharmacy, and was puzzled by Priapism's snottiness in his comments relating to the topic, as if all pharmicists and doctors that have counseled patients to be careful when switching brands of levothyroxine just said "f it, this is what I'll tell 'em."

 

[jtwcamel]

Well in NC its NTI so we have to have prescriber and pt consent to switch. As far as the data thing goes the whole money leading to this or that argument can be made with anything.

 

[Priapism321]

As far as the data thing goes the whole money leading to this or that argument can be made with anything.

So, is there data, or not? Are you saying it is OK that there is no data? Hopefully you realize how baseless your statement is when you put it into the context of our nation's health care. Because the pharmaceutical industry has the money, you are asserting that they should be able to coerce the congress and state legislatures to make it more difficult for patients to receive equally effective, cheap medications? Even with no data saying switching between the brand name drug and a generic places a patient at any more risk than you would by giving a patient Lot A of the brand one month and Lot C the next? Are you kidding me?

Do you think it is a coincidence that most companies making these claims are the manufacturers of transplant medications? This just happens to be $4 billion dollars per year worth of patents scheduled to expire in the next two years.

 

[UTPharm]

You keep asking us for DATA but you, yourself have provided us with NO data to support your claims. like me to a scientific study supporting ALL of the claims you have made. you can list several.

So, is there data, or not? Are you saying it is OK that there is no data? Hopefully you realize how baseless your statement is when you put it into the context of our nation's health care. Because the pharmaceutical industry has the money, you are asserting that they should be able to coerce the congress and state legislatures to make it more difficult for patients to receive equally effective, cheap medications? Even with no data saying switching between the brand name drug and a generic places a patient at any more risk than you would by giving a patient Lot A of the brand one month and Lot C the next? Are you kidding me?

Do you think it is a coincidence that most companies making these claims are the manufacturers of transplant medications? This just happens to be $4 billion dollars per year worth of patents scheduled to expire in the next two years.

 

[Priapism321]

You keep asking us for DATA but you, yourself have provided us with NO data to support your claims. like me to a scientific study supporting ALL of the claims you have made. you can list several.

Please refer to my very first post in this thread, detailing the numerous manufacturers of levothyroxine who have satisfied the F.D.A.'s criteria to be granted an AB rating.

Definition of AB rating: actual or potential bioequivalence problems have been resolved with adequate in vivo and/or in vitro evidence supporting bioequivalence. These are designated AB.

From here: http://www.fda.gov/cder/ob/docs/preface/ecpreface.htm#Therapeutic%20Equivalence-Related%20Terms

To furnish an example of what I consider substantive scientific data (I am starting to fear that you are unsure of what this is), I will preface with a previous post from myself several months ago on this issue:

"The drug companies would have you believe switching from brand to generic would be detrimental to the patient; however, sound scientific research argues against such a notion. In the early 1990's, a study was completed showing that Synthroid was no different than several other preparations of levothyroxine. However, since the original hypothesis was that a difference would be found, and the makers of Synthroid funded the study, they fought tooth and nail to keep the data suppressed. They were actually successful for four years, most likely leading to unnecessary prescription of Synthroid (which a court also agreed had happened, and for blocking the publication of the study, the drug company paid out over one hundred million dollars in a class action lawsuit settlement).

If anyone has a chance to read the details of this series of events (I have only provided a brief overview), you will truly appreciate how vindictive the pharmaceutical industry really is. The reason I became so interested in this stuff is the lead investigator on the study was a UCSF Pharmacist, and because she would not let the industry compromise the integrity of her research, the study was ultimately published in JAMA on April 16, 1997. In my opinion, this pharmacist has saved patients and the healthcare system hundreds of millions of dollars by demonstrating that generically equivalent formulations of levothyroxine are indeed bioequivalent to Synthroid, despite what Pharma tells anyone."

I will link to the abstract of this study; if you are not part of the peanut gallery, you know how to access the full text version.

http://www.ncbi.nlm.nih.gov/pubmed/...ez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

Have fun.

 

[RxWildcat]

Thats an interesting study, I'll reference it in the future at some point when people complain about generics.

 

[PharmDstudent]

Thats an interesting study, I'll reference it in the future at some point when people complain about generics.

When they complain about generics how? I guess you're talking about people who don't like generics for "personal" reasons. "They make me sick to my stomach. I'm allergic to generics. Why can't I take the brand? Did my doctor say that I can take a generic?... etc."

 

[RxWildcat]

Yeah, those are pretty much the people I'm talking about.