One of your medical staff is concerned about the levothyroxine product on your formulary. You carry Synthroid® and he's seen lots on reports on CNN regarding the FDA and how they're going to pull it off the market very soon unless the manufacturer proves safety and efficacy.

What do you recommend to the P&T committee - stand fast or switch? Why are you going to do one or the other?

For now, probably(?) stand fast. I'd guess it's unlikely that Abbott won't complete the necessary paperwork to get Synthroid® approved and maintain their market share, but that's just my opinion.

Some background on the issue:

1.      The FDA announced on 14 Aug 1997 that orally administered levothryoxine sodium products are new drugs and manufacturers who wish to continue to market levothryoxine sodium products had to submit new drug applications (NDAs) no later than 14 Aug 2000.  The FDA subsequently extended that deadline to 14 Aug 2001.  As strange as it may seem, levothyroxine sodium had never been formally approved by the FDA as a single-agent therapy for any indication--I guess they were "grand fathered" somehow.  Levothyroxine sodium was approved previously as an active ingredient in two NDAs (one for Thyrolar®, and one for Euthroid®). 

2.      The FDA recently approved an NDA for the Unithroid® brand of levothyroxine sodium as single agent therapy for thyroid-related disorders.  Unithroid® is the only levothyroxine sodium product listed in the FDA's Orange Book and will be the "reference listed drug" for levothyroxine sodium.  If other companies want to submit an abbreviated new drug application (ANDA) for a "generic" version of sodium levothyroxine, they are supposed to submit data showing bioequivalence to Unithroid®.

3.      Synthroid® and other brands of levothryoxine sodium now have two options to be able to continue marketing after 14 Aug 2001:

        a.  Submit an ANDA showing their product to be bioequivalent to Unithroid®.  It would then be marketed as an A-rated generic that is bioequivalent to Unithroid®.  (Note:  Until Unithroid® was approved by the FDA, companies could not submit ANDAs for levothyroxine sodium because there was no listed drug to which ANDAs could refer.)

        b.  Get an NDA filed before 14 Aug 2001.  If the NDA is approved, the drug could continue to be marketed.  There would then be multiple non-bioequivalent levothryoxine sodium products on the market (which the FDA doesn't really want to see happen).

4.      None of the levothryoxine sodium products currently on the market are A-rated to each other.  There might be products approved in the future that will be A-rated to Unithroid®.  There might also be other brands of levothryoxine sodium approved in the future through the NDA process that would not be A-rated to Unithroid®.

5.      The following is quoted from an FDA document entitled, "Guidance for Industry Levothyroxine sodium tablets - In Vivo Pharmacokinetic and Bioavailability Studies and In Vitro Dissolution Testing":

"Because of the risks associated with over- or under- treatment with levothyroxine sodium, it is critical that patients have available to them products that are consistent in potency and bioavailability."

The following websites has additional info on this topic.  http://www.fda.gov/cder/guidance/3609fnl.htm -  FDA documents/info on Synthroid®

http://abbott.com/news/press_release.cfm?id=274 - press release from Abbott

http://www.synthroid.com/patients20010712.PDF - letter to patients

http://www.synthroid.com - Abbott's web page for Synthroid®

http://www.synthroid.com/phys20010712.PDF - letter to providers regarding Synthroid®

http://www.synthroid.com/pharm20010712.PDF - letter to pharmacists regarding Synthroid®