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Oxygen and Levothyroxine

Oxygen and Levothyroxine

This paper seems to confirm what the MHRA stated in their report on levothyroxine after the Teva incident. That is, oxygen affects levothyroxine tablets. Specifically, oxygen and the amount of water bound to the levothyroxine molecules together have an even greater effect.

Not only can these cause degradation, but we have to ask what the levothyroxine will be degraded into? Could that sometimes be into substances with significant bio-activity themselves?

Pharm Dev Technol. 2013 Dec 3. [Epub ahead of print]

Impact of hydration state and molecular oxygen on the chemical stability of levothyroxine sodium.

Hamad ML, Engen W, Morris KR.


Department of Chemistry, College of Arts and Sciences, University of Hawai'i at Hilo , Hilo, HI , USA and.


Abstract Levothyroxine sodium is an important medication used primarily for treating patients with hypothyroidism. Levothyroxine sodium tablets have been recalled many times since their 1955 introduction to the US market. These recalls resulted from the failure of lots to meet their content uniformity and potency specifications. The purpose of this study is to test the hypothesis that the chemical stability of levothyroxine sodium pentahydrate is compromised upon exposing the dehydrated substance to molecular oxygen. The impact of temperature, oxygen and humidity storage conditions on the stability of solid-state levothyroxine sodium was examined. After exposure to these storage conditions for selected periods of time, high performance liquid chromatography (HPLC) was used to quantify the formation of impurities. The results showed that levothyroxine sodium samples degraded significantly over a 32-day test period when subjected to dry conditions in the presence of molecular oxygen. However, dehydrated samples remained stable when oxygen was removed from the storage chamber. Furthermore, hydrated samples were stable in the presence of oxygen and in the absence of oxygen. These results reveal conditions that will degrade levothyroxine sodium pentahydrate and elucidate measures that can be taken to stabilize the drug substance.

PMID: 24295156 [PubMed - as supplied by publisher]


As so very often, the rest of the paper is behind a paywall.

I also happened to find a PowerPoint all about levothyroxine, stability, etc. - though be warned, it is entirely based on the USA. Note particularly that it mentions "carbohydrate excipients" which would include lactose, maize starch and sucrose - all of which are included in one or more UK makes of levothyroxine.



Image is: Contents of an oxygen absorber contained within a packet of Beef Jerky - often based on iron powder, sodium chloride (common salt) and possibly activated carbon.

15 Replies

When I started taking it I read somewhere (on the leaflet that came with my levo maybe) that you should not take levo tablets out of their packing until you want to use them, think it was to keep them dry, think it also told you how they should be stored. I have a pill box that holds all my pills for the week but I never ever put my levo in it for that very reason. Looks pretty grim in those pictures doesn't it.


You are right - at least some places advise keeping the tablets in the packaging until they are to be taken. Which makes a nonsense of the situation in which people sometimes get them dished out from a bulk pack.

The issues are not only keeping it dry, but stopping it drying out too much! If you take a tablet out of the packaging and leave it in a dry atmosphere (many homes at this time of year are actually very dry) then it loses water and changes from levothyroxine pentahydrate to anhydrous levothyroxine. At that stage it seems as if it is even more likely to react with oxygen in the air. (Excessive moisture is also really bad.)

The picture isn't of the medicine - it is a sachet that is used to reduce the oxygen in a packet of beef jerky. Something that does the same thing might help with keeping levothyroxine stable.


Thanks for this information Rod. My son went into shared 24 hour care at the beginning of this week and his medication is put into blister packs by the dispensing pharmacy, even Thyroxine and I now wonder if this is bad also. Beginning to wish we hadn't gone ahead with this change. Janet.


Hi Helvalla,

I've checked my packet of Mercury Pharma Levothyroxine and it states that each tablet contains anydrous levothyroxine sodium, there's no mention of Levothyroxine pentahydrate.


All UK levothyroxine medications must express their strength/potency in terms of anhydrous levothyroxine. Using the same basis for all of them allows products which may be made with different hydration levels to be notionally equivalent.

This includes the liquid products where the levothyroxine is most certainly NOT anhydrous in the final product.

As readers of patient information leaflets, and without any other information, we simply do not know if the makers use anhydrous levothyroxine or levothyroxine pentahydrate (or some other hydration form) as an ingredient. And, in many ways, it probably doesn't matter.

Levothyroxine can gain water from or lose water to its environment.

I suspect that the purified water (another ingredient of Mercury Pharma's levothyroxine) might be sufficient to change the form present in the tablets as manufactured. But this could change again by open tablets being left out in a dry atmosphere - or on a damp window-sill.

I can imagine that one manufacturer could use anhydrous levothyroxine as an ingredient then add a bit of water. Another might use levothyroxine pentahydrate as an ingredient and not need to add the water. But if they end up with exactly the same number of molecules of levothyroxine in each tablet, does it matter?

(I am perfectly happy to believe that the hydration level of the levothyroxine as we take the tablets has lots of effects. But much less willing to believe it matters what form is tipped into the mixing bowls in the factory.)

Note: I suspect that the small change in the first liquid levothyroxine on the UK market, Kappin, was because they originally missed the requirement to use anhydrous levothyroxine as the basis for potency. When that was realised, they had to increase the potency by a small amount. The arithmetic seemed to work, but I have no other evidence.



If the people dispensing read the instructions then there is no way that levo should ever be dished out from a bulk pack. My carb came from a bulk pack and that was ok but my levo was the only drug I have had that was so specific about how it ought to be kept eats and was always dispensed in a blister pack.

What a relief to hear that wasn't the medicine! :-)


Though as the makers supply bulk packs, they must condone it being dispensed in that way.

I have only once had it like that and was utterly amazed that it happened.


How weird. Not surprised you were amazed. You do have to wonder why they bother to give instructions on how to store tablets if they do that.

Be quite interesting to find out what the manufacturers say about taking the pills out of the blister packs the night before wouldn't it.

Fascinating little gadget you found. I take CoQ10 and the pack they come in is so tough I worry about bursting the capsules when I am trying to get them out.


i have ra and hypo and my fingers are so bad i cant open the blister packs so the chemists pops them all and puts them in bottles for me ..does that mean my levo wont work properly?


I would not be too worried about short term storage - but not if it is to keep in the cupboard for months.

Maybe a device for removing pills from blister packaging would help? I did a search and found this rather expensive one (but it might be rather excellent - I don't know).


Has anyone got any specific recommendations based on experience?



thanks but i have 13 different tablets to take each morning so i need to put them in my weekly boxes...had to get others to do it for me until the chemist started putting them in bottles x



I always take my levo from the blister pack when I go to bed and put them on my bedside cabinet to take when I wake around 5.30am then go back to sleep. I do this so I do not disturb my husband by fumbling with the packet at that time. Should I stop doing this?


I don't think a few hours are going to make much of a difference. But it would be good to know for sure.


Hi Browny......I too have been organising my Levo when I go to bed as I have gone back to taking my pills in the morning and waking up and fiddling around with blister packs at 6.00am on these dark mornings with bleary eyes isn't appealing,so a pill tin was an easy answer.When I see my pharmacist I will check that out. As Helvella says.....best to know.


I also do this so I can take them in the small hours without waking up too much. Interested to know the answer, but going on how I feel since doing this, it cannot make much difference in that time.