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Once-weekly levothyroxine therapy

Once-weekly levothyroxine therapy


Posted by Thomas Repas, DO, FACP, FACE, CDE  June 30, 2009 04:35 PM

It is interesting how similar cases occasionally present in a series of pairs or triples. After not having seen hypothyroidism with persistently elevated thyroid-stimulating hormone levels while on high-dose levothyroxine therapy for several months, three cases came to see me in the same week. All had TSH >40 mIU/L despite being prescribed high-dose levothyroxine. The gentleman in my last post was not taking his levothyroxine daily because he could not afford to fill his prescription.

Later that same week, I saw a woman with mild dementia. She lives independently and has someone to help with cooking and cleaning. However, there is no one to assure that she takes her medications. Her TSH remains high because she cannot remember to take her levothyroxine and other medications every day.

Levothyroxine has an approximate seven-day half-life but the biologic effect may be longer. This means that it may be less important what exactly is taken on any particular day compared to what has been taken over the past week. Because of this, it is possible to give levothyroxine once or twice a week as directly observed therapy when necessary to ensure compliance.

There have only been a few case series with small numbers of patients reporting the safety and efficacy of once-weekly levothyroxine. Studies have shown that a single dose of as high as 3 mg of levothyroxine is well tolerated. Levels of free thyroxine are higher in the days immediately following the dose. However, as levels of T4 decrease before the next dose, peripheral conversion to active triiodothyronine becomes more efficient. Such autoregulatory mechanisms maintain euthyroidism. Patients on once-weekly therapy tolerate it well and without evidence of cardiac symptoms or toxicity. Some authors suggest that a slightly larger dose than seven times the normal daily dose may be necessary.

In the patient described above, we will first arrange to have pill boxes filled by her pharmacist. If she continues to be unable to remember to take her levothyroxine, family members have volunteered to witness her taking her levothyroxine as directly observed therapy twice a week. I rarely have to resort to once- or twice-weekly directly observed therapy. However, I have used it a few times in the past with success when all else failed.

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Comment by Tom Repas DO FACE FACP CDE -- July 10, 2009 01:50 PM

Thank you both for reading and commenting.

Maria: I cannot comment specifically on how I might dose a particular patient. Every situation is unique.

However, in general I calculate the total weekly dose in total mcg and then give half on each of the two dosing days. I don't increase unless I need to based on response to therapy. Although I later need to increase the dose in some, in others I can decrease the dose because of better compliance.

Comment by Tom Repas DO FACP FACE CDE -- July 6, 2009 10:16 AM

I agree... the data on once weekly levothyroxine is limited, with the published literature consisting of case series of only a handful of people. I am not sure such a study will ever be done because most individuals are able to take their dose every day and the need for such therapy is not often.

Thank you for all of your comments.

Comment by O KHATIB, MD, FRCP, PhD -- July 4, 2009 09:48 AM

I think availabilty, affordability and accessability are important issues particularly among elderly people and I totally agree with once-weekly thyroxine tablet but a clinical study is needed to confirm the use of once weekly thyroxine.

Comment by Maria Soledad Z. Goic -- July 2, 2009 10:35 AM

Dr. Repas, how much T4 will you prescribe for the woman which is going to take the pills twice a week? Three and a half times the daily dose? Or as you said, a slightly larger dose such as four times? Thanks!

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