Problems with generic stimulants

[PikminOC]

With the newer generic adderall xr and adderall formulations, patients have been stating they are not working as well, are not as effective. Have you noticed this or gotten complaints from people about this? Any references or reports you have regarding this.

This happened with generic concerta when it came out also.

---

Members don't see this ad.

 

[fcrc]

With Concerta there is only 1 generic manufacturer that is AB equivalent (Watson) as far as I know, so it makes sense if they got a different manufacturer of generic methylphenidate. I've never had a patient complain about generic Adderall/XR . . . I think most of the generics of Adderall/XR are AB rated.

 

[PikminOC]

Apparently teva has been making less effective ones.
And shire only recently lost their patent and have a class action against them regarding trying to block generic add xr. The generics haven't been as good.

 

[Digsbe]

Generics sell for less on the street so they "don't work as well"

 

[PikminOC]

I use understand your being jaded, but my patients see me regularly and this only came up recently.

There are many recent generic stims that have these issues.

My patients aren't asking for branded. They are asking which generics are better. I'm trying get proof for them.
Any evidence you guys get will be helpful

 

[WVUPharm2007]

No, many recent generic stimulants do not have these issues. The one generic for Concerta isn't AB rated and apparently this as made you now think they are all a problem. It's likely nocebo. There is a reason why it's always psych meds whose generics "don't work."

 

[radio frequency]

Absolutely no patient has ever complained to me that the generic Adderall XRs don't work as well. Which is funny because I've heard complaints about specific clonidine generics...you'd expect I'd hear about Adderall XR of there was an issue for even a few patients.

 

[Sine Cura]

People really need to brush up on the concept of authorized generic: 42 CFR 447.506 - Authorized generic drugs.

You can't have authorized generics be AB rated to the brand because they have the same NDA.

Teva and Global Adderall XR generic are authorized generics (just the imprints are different). The Global stock bottles even mention Shire.

Same goes for Watson/Actavis methylphenidate ER (FFS look at the Alza imprint).

 

[PikminOC]

As physicians we hear it once in a while. But now a few patients told me this. Do they tell their pharmacist?
If you google this, alot comes up. These are long term stable patients.

 

[Dr Wario]

If there was quality documentation that a particular generic was not comparable to the branded item, the generic would lose its AB rating (such as what happened with kremers brand of methylphenidate er). We are not saying that such a thing can not happen, what we are saying is that we really can't help you with good documentation because if good evidence was available, we already could not substitute that particular manufacturer for the brand.

Oh and yes we get complaints every day about generics not working as well as the brand, one in awhile we get complains of the brand not working as well as the generic (Opana ER...wonder why that is? hmm).

 

[PikminOC]

No one is saying they aren't authorized generics. Just that some of them aren't working as well for the pt

 

[Sine Cura]

One would have to define what is a "newer" formulation, what is "effective" and what is "not working as well," and which ones

For example, Shire Adderall (IR) hasn't been on the market in a while and the ANDAs available are not exactly new. The Teva IR is not brand Adderall in an NDA sense despite the labeling, so it doesn't really make sense to call it a "newer" version of brand Adderall.

As for the ANDAs for Adderall XR, there is the Actavis one that is fairly new and more recently a Global/Impax ANDA just approved this year that I just found about as I've never been asked about it. The Teva one is an authorized generic.

Generics are almost never compared head to head in terms of relative efficacy... it is not unheard of someone getting a different labeler's product due to what is "preferred" by the chain pharmacy and experiencing a difference but it's hard to draw conclusions about one labeler's product versus another's just from anecdotes

 

[PikminOC]

Correct. That is why I'm asking you guys as I figure you have more information on this than I do.

 

[PikminOC]

What is Anda and nda?

 

[ldiot]

People really need to brush up on the concept of authorized generic: https://www.law.cornell.edu/cfr/text/42/447.506

You can't have authorized generics be AB rated to the brand because they have the same NDA.

Teva and Global Adderall XR generic are authorized generics (just the imprints are different). The Global stock bottles even mention Shire. Patients complaining are full of ****.

Same goes for Watson/Actavis methylphenidate ER (FFS look at the Alza imprint).

This makes no sense... don't all new generics apply with an ANDA? Why would using the clinical trial data from the name brand drug in the application prevent a generic from being AB rated?

How can an authorized generic not be AB rated? Aren't they the same thing?

 

[PikminOC]

I never had a complaint for non-AB rated Concerta, except when I work in rich, white areas...
Seriously, if people are complaining about the amount of methylphenidate and it's release, I don't think that's the main problem that should be addressed. Honestly, a fu*king slap in the face is needed. Put them in a third world country to face real problems.

 

[Sine Cura]

This makes no sense... don't all new generics apply with an ANDA? Why would using the clinical trial data from the name brand drug in the application prevent a generic from being AB rated?

How can an authorized generic not be AB rated? Aren't they the same thing?

Exactly. The authorized generic is the same freaking thing so how can the same thing be AB-rated to itself? An authorized generic doesn't have an approval pathway like ANDA because there is not a need to compare itself to itself.

 

[BidingMyTime]

What is Anda and nda?

abbreviated new drug application and new drug application. The simple explanation of the difference between them is the ANDA only has to show that its bioequivalent to the NDA....it doesn't have to show all the effectiveness & safety that the NDA would have to show.

 

[PikminOC]

My patients aren't asking for increase in dose. They are asking for better generics to request from pharmacy

 

[zelman]

What is Anda and nda?

NDA = new drug application

This is the $2M application to the FDA to be allowed to sell your drug. It includes studies that show it to be safe and effective to treat one or more conditions.

ANDA = abbreviated new drug application

This is the $500K application to the FDA to be allowed to sell a drug you made that should be the same as someone else's. It does not include the above studies. Instead, there are studies showing that your drug has similar pharmacokinetics to the previously approved product (exact tests will vary based on the product: e.g. a generic tablet should show that it dissolves as the brand name does, but an IM solution won't show that). It relies on the brand name to show the safety/efficacy.

The point was brought up that when one company makes both a brand and generic product (an "authorized generic"), they do not need to do the studies as part of the ANDA since they are the same thing with different markings.

Another point was mentioned that if anyone here had any hard evidence to show that the generic drugs had any material difference from the brand name product, that evidence would cause the FDA to change the equivalence status of that generic. Also, the ANDA does not require different generics to show they are similar to one another. They all just compare themselves to the "reference product" (a.k.a. brand name). So, theoretically, there can be double the variation between two generics as there can between a brand and generic.

 

[Dr Wario]

My patients aren't asking for increase in dose. They are asking for better generics to request from pharmacy

I would by highly cautious about every telling patients to request a specific brand of a CII from a pharmacy, unless the person is an extremely good/long standing customer with many non-controls, that is likely to get them instantly banned.

 

[RxPreceptor]

There's only so much safe space (not that it's required) for catering to non objective claims. I'll throw it back at you and ask how you know whether it's the drug or the disease state responsible for the "change".

 

[PikminOC]

When it's more than one patient in my small practice, Im concerned.

 

[PikminOC]

This has been a problem with antiseizure and thyroid meds. Why not stims?

 

[trailerpark]

My pharmacy won't order specific brands of C2 for people. You get what we have or go elsewhere.


Sent from my iPhone using SDN mobile app

 

[zelman]

This has been a problem with antiseizure and thyroid meds. Why not stims?

When is the last time you ordered a blood test to check the amphetamine level of a patient?

That's why. Therapy is not guided by exact levels in ADHD. Everything is ballparked. You can alter the pharmacokinetics of amphetamines by eating baking soda or drinking orange juice. It's far from an exact science and the tolerances built into the generic approval process SHOULD be good enough. They may not be (e.g. generic Wellbutrin XL 300mg) and the easiest way to challenge that is to have a lot of consumers complain the the FDA that a particular brand is substandard. That's how the concerta issue was identified.

 

[PikminOC]

When is the last time you ordered a blood test to check the amphetamine level of a patient?

That's why. Therapy is not guided by exact levels in ADHD. Everything is ballparked. You can alter the pharmacokinetics of amphetamines by eating baking soda or drinking orange juice. It's far from an exact science and the tolerances built into the generic approval process SHOULD be good enough. They may not be (e.g. generic Wellbutrin XL 300mg) and the easiest way to challenge that is to have a lot of consumers complain the the FDA that a particular brand is substandard. That's how the concerta issue was identified.

that why I'm asking you guys. U may have heard more info. U are in the know. I figure they complain to me and pharmacy first

 

[PikminOC]

My pharmacy won't order specific brands of C2 for people. You get what we have or go elsewhere.


Sent from my iPhone using SDN mobile app

correct. But they are trying to figure out which generic. They can switch pharmacies

 

[zelman]

that why I'm asking you guys. U may have heard more info. U are in the know. I figure they complain to me and pharmacy first

Yeah. I haven't really heard anything, but they can still let the FDA know. They may be hesitant to speak to pharmacists for fear of looking like drug diverters.

 

[PikminOC]

Exactly. I'm glad you understand the conundrum. How to report to fda?

 

[genesis09]

You can use FDA medwatch but I believe they look more at the drug than manufacturer when looking at the reports. http://www.fda.gov/Safety/MedWatch/default.htm

 

[y0ssarian87]

Exactly. I'm glad you understand the conundrum. How to report to fda?

I think you may be looking for this:

https://www.accessdata.fda.gov/scripts/medwatch/index.cfm?action=reporting.home

Health care professionals and consumers/patients may fill out Medwatch reports. The Office of Surveillance and Epidemiology assess reports and look for signals that may indicate something is wrong with a product formulation. A common report is loss/lack of efficacy, which would be appropriate in the scenarios you described of generics not working as well.

The research behind identifying when a generic isn't working is still evolving. As has been hashed out here, for those involved in pharmacovigilance it can be difficult to assess loss of efficacy in disease states like ADHD and depression where efficacy is often based on patient-reported outcomes and where there is a high placebo response rate, especially compared to disease states like epilepsy where independently-identifiable events (i.e., seizures) can be used to assess outcomes and placebo response rates are low. ADHD and depression represent disease states where there is a low signal-to-noise ratio when looking at efficacy. Epilepsy would be an example of a state where there is a high signal-to-noise ratio. There are some attempts to incorporate pharmacokinetic modeling to these assessments to create scoring systems to help identify true signals. But despite all the best attempts at creating ways to identify when an issue arises, nothing meaningful can come from it unless providers and patients submit reports when there are issues.


Sent from my iPhone using SDN mobile app

 

[y0ssarian87]

You can use FDA medwatch but I believe they look more at the drug than manufacturer when looking at the reports. http://www.fda.gov/Safety/MedWatch/default.htm

Ah, beat me to it! But they can look at manufacturer when the NDC is provided. Good quality reports with detailed information are needed to get to that level of scrutiny. However many (most) providers have no incentive to spend their time submitting these reports and acting as an investigator.


Sent from my iPhone using SDN mobile app

 

[BidingMyTime]

This has been a problem with antiseizure and thyroid meds. Why not stims?

some thyroid and antiseizure meds are "narrow therapeutic index" drugs, stimulants are not. A very small change in narrow tharapeutic index drugs, can have big changes in a patient. Most drugs are not narrow therapeutic, so small changes have no effect on their effectiveness.

 

[zelman]

some thyroid and antiseizure meds are "narrow therapeutic index" drugs, stimulants are not. A very small change in narrow tharapeutic index drugs, can have big changes in a patient. Most drugs are not narrow therapeutic, so small changes have no effect on their effectiveness.

While this is true, never make this argument. People will claim that the way they respond to the drug is like an NTI drug and the list of "NTI drugs" is arbitrary or incomplete. See above where I brought up checking serum drug concentrations? That's saying the same thing in a way that's harder to argue against.

 

[Digsbe]

I use understand your being jaded, but my patients see me regularly and this only came up recently.

There are many recent generic stims that have these issues.

My patients aren't asking for branded. They are asking which generics are better. I'm trying get proof for them.
Any evidence you guys get will be helpful

Sorry if I seem jaded. I've just not read any literature or heard of reports where generic stimulants with AB rating were less effective in patients than the brand. I'd wonder if they are taking them the same way or at the same time as before and if there aren't any other changed variables beyond the drug that have occurred.

 

[PikminOC]

That's a lot of info they ask for.

 

[owlegrad]

This guy is just the best ever. Be honest, did you know it was literally the exact same product from the exact same manufacturer when you started this thread? You did, didn't you? The entertainment value is high with this one.

What I always told my patient's when they brought up the Wellbutrin example is, that it is proof the system works. There was a problem and that problem was identified and rectified.

 

[Carboxide]

This has been a problem with antiseizure and thyroid meds. Why not stims?

It actually hasn't. It's all nocebo effects. There have been crossover studies done with ultra narrow therapeutic index drugs (tacrolimus comes to mind) that found there is no difference between the two groups and that patients are unable to tell the difference either.

The idea of thyroid/seizure/coumadin/immunosuppressant drugs needing to be a certain brand is a myth that has never been substantiated.

You always come on here, ask a question, and then vehemently disagree with whatever we say. Why do you even ask if you don't want to know the actual answer?

 

[PikminOC]

It was a 55 yo lady. You guys make alot of assumptions. They had switched pharmacies so I guess the generics were different.
And as another poster above said, they may not want to report it to the pharmacist. Given the way most of you respond on here, now I understand why.

 

[Carboxide]

No one is saying they aren't authorized generics. Just that some of them aren't working as well for the pt

You don't understand what an authorized generic is. It's not the same as a regular generic product. An authorized generic is when the company that makes the brand also makes a generic version - in other words, they just stamp it with a different name (sometimes). When Protonix went generic I had a patient complain it wasn't working as well. She was receiving the authorized generic. It had the name "Protonix" stamped on the side. They literally just put it into two different bottles.

Teva is the exact same as the brand name product. Exactly. Because it is made by the same people in the same factory in the same company with the same machines and same employees and same management and same testing processes. It is EXACTLY the same product.

 

[PikminOC]

Sorry if I seem jaded. I've just not read any literature or heard of reports where generic stimulants with AB rating were less effective in patients than the brand. I'd wonder if they are taking them the same way or at the same time as before and if there aren't any other changed variables beyond the drug that have occurred.

I do ask them about other variables. We go over those things.

And while the system may work, there are people effected during these stages.

 

[WVUPharm2007]

You don't understand what an authorized generic is. It's not the same as a regular generic product. An authorized generic is when the company that makes the brand also makes a generic version - in other words, they just stamp it with a different name (sometimes). When Protonix went generic I had a patient complain it wasn't working as well. She was receiving the authorized generic. It had the name "Protonix" stamped on the side. They literally just put it into two different bottles.

Teva is the exact same as the brand name product. Exactly. Because it is made by the same people in the same factory in the same company with the same machines and same employees and same management and same testing processes. It is EXACTLY the same product.

Again -- it's typically nocebo.

 

[PikminOC]

Once again these are stable patients who were doing well on the meds. I have had these patients for years

 

[WVUPharm2007]

Once again these are stable patients who were doing well on the meds. I have had these patients for years

...and?

Drugs that affect mood, attention, and other overt body sensations are the most susceptible to nocebo. We aren't saying they are unstable. It's surprisingly common. We see this **** all the time. People take something they notice is different. They wonder if it is really the same thing. They become hypervigilant about their mood, attention span, etc. They begin noticing things they wouldn't otherwise. What do they blame? Oh, must be the new generic. And then when you start throwing *authorized* generics into the mix, it becomes pretty obvious what the real story is. And it ain't the drug.

 

[PikminOC]

I know exactly what you are talking about. However, I have had several people with this complaint recently with these meds. I spend a lot of time with patients and I try to help them by posting and looking for additional information.
I would not have posted here otherwise. You guys are very helpful to me. I appreciate your info.

 

[Carol is Alpha]

http://www.peoplespharmacy.com/2015/03/02/is-the-fda-protecting-drug-companies-instead-of-patients/

 

[beautifulrobot]

I know exactly what you are talking about. However, I have had several people with this complaint recently with these meds. I spend a lot of time with patients and I try to help them by posting and looking for additional information.
I would not have posted here otherwise. You guys are very helpful to me. I appreciate your info.

I would encourage you to submit a MedWatch report about this issue. A high quality report would include the name of the drug manufacturer of the drug that worked, how long the patient had been on the drug that worked, when did the patient switch to the drug that doesn't work, the name of the new manufacturer of the drug that doesn't work, when did the patient begin to experience lack of effect, what symptoms did the lack of effect include, and what was done to treat the lack of effect, e.g. is the lack of effect still ongoing? was the patient switched back to the old drug manufacturer and did that resolve the lack of effect problems? Was the patient rechallenged with the new drug manufacturer and experience the same lack of effect issues? Including an accurate, detailed timeline of events and outcomes is key. Have the drug manufacturer of both the drug that work and the drug that didn't work is key. It will also be helpful if you mention that you ruled out other factors such as changes in diet, major life events that would affect disease progression, etc. Submit a separate report for each individual patient. You can mention in the report that you are submitting X amount of reports for X different patients, and that this is report 1 out of X, 2 out of X, etc. But if you submit just one report for several patients it will not be as helpful.

I realize it is time consuming, but if you truly want to get to the bottom of this, the best thing to do is to submit high quality reports directly to the FDA. They are the only ones who can actually investigate the issue and verify whether there is a quality assurance problem with a specific generic. It would be a better use of your time than looking for anecdotal information on SDN.

Another resource is the FDA's Division of Drug Information. You can call them and ask them the same questions you are asking here, and they will be able to give you a more authoritative answer:
(888) 463-6332

 

[npage148]

This hurts my heard. We tell you that the teva and brand are identical (ever look at the capsules) and you refuse to accept its a patient issue experiences a problem with a drug with twitchy Pk and tolerance issues. It's not surprising that only rich people and people with psych drugs have issues with generics.

If a drug is AB rated I will very rarely indulge a customers/doctors issues with generics. Doesn't matter if it's narrow TI or not. If they don't understand the FDA BE approval process how can they argue a generic is bad. Oh that's right, a drug rep said so.

 

[PikminOC]

This hurts my heard. We tell you that the teva and brand are identical (ever look at the capsules) and you refuse to accept its a patient issue experiences a problem with a drug with twitchy Pk and tolerance issues. It's not surprising that only rich people and people with psych drugs have issues with generics.

If a drug is AB rated I will very rarely indulge a customers/doctors issues with generics. Doesn't matter if it's narrow TI or not. If they don't understand the FDA BE approval process how can they argue a generic is bad. Oh that's right, a drug rep said so.

They switched pharmacies. I'm not sure, nor is the patient about the manufacturer. The pharmacist would know but the patient is afraid to ask. They said it's a different pill. I don't know enough about this. I don't keep track of manufacturers, lot numbers, etc.
Does only teva make the generic? No other manufacturers? That would help if I knew that.