UP­DAT­ED: FDA and its re­search take aim at thy­roid as­so­ci­a­tion's guide­line on not us­ing levothy­rox­ine gener­ics

Gener­ic drugs rep­re­sent the vast ma­jor­i­ty of all drugs pre­scribed in the US.

But in some unique cas­es, the FDA ac­knowl­edges that there are doc­tors who are con­cerned about drugs with a nar­row ther­a­peu­tic win­dow (i.e., as the FDA says, “drugs where small dif­fer­ences in dose or blood con­cen­tra­tion may lead to se­ri­ous ther­a­peu­tic fail­ures or ad­verse drug re­ac­tions”), and there­fore may be more like­ly to pre­scribe brand-name prod­ucts over gener­ics in some cas­es.

But in one in­stance, where the Amer­i­can Thy­roid As­so­ci­a­tion (ATA) rec­om­mends that gener­ics not be used in some in­stances when the thy­roid hor­mone levothy­rox­ine is used, the FDA is now point­ing to new FDA-fund­ed re­al-world re­search that shows how switch­ing be­tween gener­ics proved to be sim­i­lar to stick­ing with the brand-name coun­ter­part.

For the study, the re­searchers dove in­to an ad­min­is­tra­tive claims data­base that linked lab test mea­sures of thy­roid func­tion of pa­tients un­der­go­ing treat­ment for hy­pothy­roidism with levothy­rox­ine, iden­ti­fy­ing and match­ing two dif­fer­ent pop­u­la­tions to com­pare the ef­fects of gener­ic switch­ing to sin­gle-prod­uct use.

“Their con­clu­sion is that switch­ing among dif­fer­ent gener­ic levothy­rox­ine prod­ucts was not as­so­ci­at­ed with clin­i­cal­ly sig­nif­i­cant changes in thy­roid func­tion (as in­di­cat­ed by sub­group av­er­age serum thy­rotropin lev­el). The re­searchers’ con­clu­sion — al­though ful­ly con­sis­tent with FDA pre­cepts of bioe­quiv­a­lence and, at the phar­ma­cy lev­el, prod­uct in­ter­change­abil­i­ty it­self — con­flicts with cur­rent ATA guide­line rec­om­men­da­tions that warn clin­i­cians about po­ten­tial changes in thy­roid func­tion as­so­ci­at­ed with levothy­rox­ine prod­uct switch­ing,” the agency ex­plained yes­ter­day.

Pri­or to ini­ti­at­ing this study, the re­searchers, in­clud­ing some from the Mayo Clin­ic and FDA, not­ed how the ATA even ques­tioned the FDA’s meth­ods for de­ter­min­ing bioe­quiv­a­lence be­tween levothy­rox­ine prod­ucts.

And while the ATA guide­lines rec­om­mend us­ing thy­rotropin lev­els as the bio­mark­ers for eval­u­at­ing ther­a­peu­tic equiv­a­lence, in the ab­sence of such ev­i­dence the ATA rec­om­mends that pre­scribers avoid switch­ing be­tween levothy­rox­ine prod­ucts in the treat­ment of hy­pothy­roid pa­tients. As a re­sult of that rec­om­men­da­tion, brand-name levothy­rox­ine was pref­er­en­tial­ly pre­scribed over gener­ic levothy­rox­ine prod­ucts, the FDA ex­plains.

“Re­sults of this com­par­a­tive ef­fec­tive­ness re­search study sug­gest that switch­ing among dif­fer­ent gener­ic levothy­rox­ine prod­ucts was not as­so­ci­at­ed with clin­i­cal­ly sig­nif­i­cant changes in TSH lev­el,” the re­searchers wrote in con­tra­dic­tion to the guide­line.

And al­though the re­searchers were care­ful to point out that their study was not de­signed to as­sess the ther­a­peu­tic equiv­a­lence of levothy­rox­ine gener­ics and brand-name ver­sions, the FDA added yes­ter­day that this CDER-spon­sored re­search “sug­gests that there may be in­sti­tu­tion­al re­sis­tance among some stake­hold­ers that may not be sup­port­ed by re­al-world ev­i­dence.”

The ATA lead­er­ship told End­points News via email:

The ATA finds this study re­as­sur­ing for pa­tients and clin­i­cians. The ATA will in­clude this study in the sys­tem­at­ic re­view they con­duct in prepa­ra­tion for their next up­date of their hy­pothy­roidism guide­lines. Mean­while not all levothy­rox­ine prod­ucts (all brands and all gener­ics) have been com­pared with each oth­er in rig­or­ous bioe­quiv­a­lence test­ing. So it re­mains rea­son­able for clin­i­cians to be alert for al­tered thy­roid sta­tus in in­di­vid­u­als who have their levothy­rox­ine prod­ucts switched, and con­sid­er re-check­ing a pa­tients thy­roid func­tion tests if the clin­i­cal sit­u­a­tion sug­gests that the pa­tient may have de­vel­oped symp­toms of ei­ther un­der­treat­ment or overtreat­ment of their hy­pothy­roidism.

Ed­i­tor’s note: Ar­ti­cle up­dat­ed with com­ment from the ATA.

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AJ Patel was recovering from a complicated brain surgery when his oncologist burst into the hospital room yelling, “I’ve got some really great news for you!”

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“What are you talking about?” Patel asked. He had never seen an oncologist so happy.

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On one hand, US patient advocacy groups rated the industry higher-than-ever overall. More than two-thirds (67%) of groups gave the industry a thumbs up for 2021, a whopping 10 percentage point increase over the year before, according to the PatientView annual study, now in its 9th year.

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Pivotal data from the ELEVATE program in ulcerative colitis — which consists of two Phase III trials, one lasting 52 weeks and the other just 12 weeks — illustrate an “encouraging balance of efficacy and safety,” according to Michael Corbo, chief development officer of inflammation & immunology at Pfizer. The company is presenting the results as a late breaker at Digestive Disease Week.

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