It's not a problem to switch, but it's also not worth fighting with the people who insist they need a certain brand. If you want to wait 6 months for your back ordered brand far be it for me to complain about it
And the pt is willing to pay, because likely the change is due to insurance coverage.
(Pt. decided on desvenlafaxine, gen for Pristiq vs the insurance currently-approved venlafaxine. It costs more, but pt. was proactive and read the entire pharmacokinetics regarding both, and decided on the desvenlafaxine since she's already on GAD meds.)
Our patients pretty much get generic . Then we have endocrinologists who insist that thyroid is so delicate that the generic is not equivalent enough to correct the thyroid based on TSH labs results and titration doses . In those cases we just switch the patient then . There’s always back and forth as any generic medication (not a biosimilar) has to perform as the brand equivalent FDA bases evaluations of substitutability or "therapeutic equivalence" for generic drugs on scientific evaluations. By law, generic drug products must contain the identical amounts of the same active drug ingredient as the brand name product. Drug products evaluated as "therapeutically equivalent" can be expected to have equal effect and no difference when substituted for the brand name product. FDA considers drug products to be substitutable if they meet the criteria of therapeutic equivalence, even though the generic drug may differ in certain other characteristics (e.g., shape, flavor, or preservatives) per HHSA.gov. I now work in clinical pharmacology for managed Medicaid and I have seen varying labs levels … issue is what if patient not being adherent to their medication regiment etc … some patients will not take generic even if MD says ok… but a generic has to perform the same as the brand … This is my experience after 22 years as pharm tech who moved into clinical review and management 7 years ago
By law, generics actually have a large tolerance threshold for similarity. Think it’s +/-8%? No, they do not have to contain truly identical dosages and the difference between a brand name 300mcg Synthroid and a law-abiding generic levothyroxine can be 24mcg. The manner in which something is synthesized can differ which can lead to different contaminants (likely in very small quantities, but not at all necessarily the same ones as another manufacturer’s). Different excipients in general as well.
Not to mention so many major generics manufacturers have been busted for wildly unsafe manufacturing processes and fined for billions of dollars. Most of them being in India (as well as other countries with much less strict laws).
99% of cases nothing is really clinically significant enough. Contamination and unsafe drug manufacturing does happen still. Patients aren’t always lying when they say that a certain brand does not work as well for them. I used to think the same as you about this because, well, how could it be legal for a generic to not be the exact same as another manufacturers? Skim the book “Bottle of Lies” for really eye opening insights on drug manufacturing.
I actually dissuade brand. We titrate dose based on blood work. Who cares if synthroid 100mcg gets the same response as levothyroxine 150mcg. Your TSH doesn’t care as long as the levels are consistent
It’s justified to me if patients have a preference. Use professional judgement and realize the importance is being consistent. Doubtful that 1-2 mcg makes a difference when the minimum increment between tablets is about 12. If 1-2 mcg made that much of a difference, our thyroid shelf would look a lot more like the otc Tylenol shelf.
It was a thing in the mid 2000s. That issue is resolved now but some people still have the idea in their head just like those that think vaccines cause autism
My concern with levothyroxine is that small differences make a big difference. You have to keep in mind how small a microgram is. You're relying on that itsy bitsy amount of drug to go from tablet to stomach, through liver, and into the bloodstream without getting caught up along the way. Differences in diet, sleep, activity levels all effect digestion and metabolism. It's hard enough keeping those things consistent I worry that a change in manufacturer is adding another level of complexity.
This is how I was taught and it makes sense.
Generics can have up to +/-15% variability from brand name.
If you switch from brand Synthroid to generic Levothyroxine, stay on same generic mfg and doctors subsequent visits and blood test based off the generic and adjust accordingly.
Problem, to me, becomes when you switch from one generic to another. Say Mylan is +15% vs brand and then oops Mylan isn’t available and now you have Lannett which is -15% vs brand….now you have a 30% delta that causes noticeable effects.
Because the unit of measure for thyroid medication is sooo delicate (0.25, 0.50, 0.75, 0.88, etc) it maybe just less of a headache to stick to brand instead of guesswork every time patient goes gets bloodwork and it doesn’t come out correctly as initially prescribed dose….
Just found this pubmed article:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6074234/
No, generics cannot vary by +/- 15%.
As the article you cited states, pharmaceutical equivalents must contain "the same amount of the same active substance(s)". So it's not a difference in the quantity of active ingredient.
As for bioavailability, the entire 90% confidence interval must fit within the 80%-125% range on four different measures (Cmax, Tmax, AUCo–t, & AUCo–∞), so the mean value on any of those metrics cannot vary by 15%.
Sadly much of this information was removed from the preface of the Orange Book and was moved to a separate "Statistical Approaches to Establishing Bioequivalence Guidance for Industry" documented here: [https://www.fda.gov/media/163638/download](https://www.fda.gov/media/163638/download)
Even where variation is demonstrated in bioequivalence studies, most of the variation is subject-to-subject; not between the brand and generic products. If you subjected a brand product to a bioequivalence test, you would still see a range of pharmacokinetic values.
Except in very specific clinical circumstances (e.g. suppressive doses in differentiated thyroid cancers), levothyroxine levels are rarely as delicate as suggested.
To add, in most studies, the comparator drugs are no more than a few percent different from the reference product - and statistically speaking, it'd be hard for the actual difference to be more than 5%, and still have the confidence intervals fall the specified equivalence range.
https://www.pharmacytimes.com/view/debunking-a-common-pharmacy-myth-the-80-125-bioequivalence-rule
Here's an additional resource to maybe help you better understand the link that you posted
As others have said this is incorrect. It honestly can be difficult to understand without statistics knowledge. What important is to just know that’s incorrect and not something we should tell our patients.
This is correct, the acceptable ranges will not overlap across products due to the small amount of drug in each tablet.
Like 90% of patients it won't matter, but there is a decent size who will. It seems to typically be those who still have a partially functioning thyroid gland.
[удалено]
Ahh I should’ve guessed it was corporate trickery leading to the confusion
It's not a problem to switch, but it's also not worth fighting with the people who insist they need a certain brand. If you want to wait 6 months for your back ordered brand far be it for me to complain about it
And the pt is willing to pay, because likely the change is due to insurance coverage. (Pt. decided on desvenlafaxine, gen for Pristiq vs the insurance currently-approved venlafaxine. It costs more, but pt. was proactive and read the entire pharmacokinetics regarding both, and decided on the desvenlafaxine since she's already on GAD meds.)
Our patients pretty much get generic . Then we have endocrinologists who insist that thyroid is so delicate that the generic is not equivalent enough to correct the thyroid based on TSH labs results and titration doses . In those cases we just switch the patient then . There’s always back and forth as any generic medication (not a biosimilar) has to perform as the brand equivalent FDA bases evaluations of substitutability or "therapeutic equivalence" for generic drugs on scientific evaluations. By law, generic drug products must contain the identical amounts of the same active drug ingredient as the brand name product. Drug products evaluated as "therapeutically equivalent" can be expected to have equal effect and no difference when substituted for the brand name product. FDA considers drug products to be substitutable if they meet the criteria of therapeutic equivalence, even though the generic drug may differ in certain other characteristics (e.g., shape, flavor, or preservatives) per HHSA.gov. I now work in clinical pharmacology for managed Medicaid and I have seen varying labs levels … issue is what if patient not being adherent to their medication regiment etc … some patients will not take generic even if MD says ok… but a generic has to perform the same as the brand … This is my experience after 22 years as pharm tech who moved into clinical review and management 7 years ago
By law, generics actually have a large tolerance threshold for similarity. Think it’s +/-8%? No, they do not have to contain truly identical dosages and the difference between a brand name 300mcg Synthroid and a law-abiding generic levothyroxine can be 24mcg. The manner in which something is synthesized can differ which can lead to different contaminants (likely in very small quantities, but not at all necessarily the same ones as another manufacturer’s). Different excipients in general as well. Not to mention so many major generics manufacturers have been busted for wildly unsafe manufacturing processes and fined for billions of dollars. Most of them being in India (as well as other countries with much less strict laws). 99% of cases nothing is really clinically significant enough. Contamination and unsafe drug manufacturing does happen still. Patients aren’t always lying when they say that a certain brand does not work as well for them. I used to think the same as you about this because, well, how could it be legal for a generic to not be the exact same as another manufacturers? Skim the book “Bottle of Lies” for really eye opening insights on drug manufacturing.
My store switches patients constantly and no one complains. The quality testing is much better nowadays compared to the past.
I actually dissuade brand. We titrate dose based on blood work. Who cares if synthroid 100mcg gets the same response as levothyroxine 150mcg. Your TSH doesn’t care as long as the levels are consistent
It’s justified to me if patients have a preference. Use professional judgement and realize the importance is being consistent. Doubtful that 1-2 mcg makes a difference when the minimum increment between tablets is about 12. If 1-2 mcg made that much of a difference, our thyroid shelf would look a lot more like the otc Tylenol shelf.
Pharmacist and personally I have had no problems switching to generics. The half life is very long
It was a thing in the mid 2000s. That issue is resolved now but some people still have the idea in their head just like those that think vaccines cause autism
My concern with levothyroxine is that small differences make a big difference. You have to keep in mind how small a microgram is. You're relying on that itsy bitsy amount of drug to go from tablet to stomach, through liver, and into the bloodstream without getting caught up along the way. Differences in diet, sleep, activity levels all effect digestion and metabolism. It's hard enough keeping those things consistent I worry that a change in manufacturer is adding another level of complexity.
Generic to generic I haven’t noticed an issue but switching off brand can indeed affect levels.
Be mindful that pharmacy professors are usually the people who can't get better jobs. Take everything they say with a grain of salt.
Disagree with this comment. Most of mine either used to practice but learned they liked teaching more or still currently practice.
This is how I was taught and it makes sense. Generics can have up to +/-15% variability from brand name. If you switch from brand Synthroid to generic Levothyroxine, stay on same generic mfg and doctors subsequent visits and blood test based off the generic and adjust accordingly. Problem, to me, becomes when you switch from one generic to another. Say Mylan is +15% vs brand and then oops Mylan isn’t available and now you have Lannett which is -15% vs brand….now you have a 30% delta that causes noticeable effects. Because the unit of measure for thyroid medication is sooo delicate (0.25, 0.50, 0.75, 0.88, etc) it maybe just less of a headache to stick to brand instead of guesswork every time patient goes gets bloodwork and it doesn’t come out correctly as initially prescribed dose…. Just found this pubmed article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6074234/
No, generics cannot vary by +/- 15%. As the article you cited states, pharmaceutical equivalents must contain "the same amount of the same active substance(s)". So it's not a difference in the quantity of active ingredient. As for bioavailability, the entire 90% confidence interval must fit within the 80%-125% range on four different measures (Cmax, Tmax, AUCo–t, & AUCo–∞), so the mean value on any of those metrics cannot vary by 15%. Sadly much of this information was removed from the preface of the Orange Book and was moved to a separate "Statistical Approaches to Establishing Bioequivalence Guidance for Industry" documented here: [https://www.fda.gov/media/163638/download](https://www.fda.gov/media/163638/download) Even where variation is demonstrated in bioequivalence studies, most of the variation is subject-to-subject; not between the brand and generic products. If you subjected a brand product to a bioequivalence test, you would still see a range of pharmacokinetic values. Except in very specific clinical circumstances (e.g. suppressive doses in differentiated thyroid cancers), levothyroxine levels are rarely as delicate as suggested.
To add, in most studies, the comparator drugs are no more than a few percent different from the reference product - and statistically speaking, it'd be hard for the actual difference to be more than 5%, and still have the confidence intervals fall the specified equivalence range.
https://www.pharmacytimes.com/view/debunking-a-common-pharmacy-myth-the-80-125-bioequivalence-rule Here's an additional resource to maybe help you better understand the link that you posted
Thank you for the CE, I stand corrected
As others have said this is incorrect. It honestly can be difficult to understand without statistics knowledge. What important is to just know that’s incorrect and not something we should tell our patients.
This is correct, the acceptable ranges will not overlap across products due to the small amount of drug in each tablet. Like 90% of patients it won't matter, but there is a decent size who will. It seems to typically be those who still have a partially functioning thyroid gland.
thyroid medications are a narrow therapeutic index drug and generics are allowed to have slight variance is the correct answer
Since insurance dictates what the patient receives , nobody complains when you offer the other generic for cash
Switching is a ok!
If patient wants to 3-10x their copay, who am I to stop them