Medicine Expiry - an illustration

[helvella]

There are frequent questions about potency of medicines beyond expiry.

In order to illustrate the effect of exceeding expiry dates, I have calculated a series of figures showing remaining percentage potency. UK potency requirements for levothyroxine are that it remains in the range 90 to 105% from manufacture to expiry date.

This is just a simple arithmetic exercise. It does not take into account the complexity of real world medicines. (Percentages have been rounded down for display purposes.)

Assume that a medicine, when first made, is exactly at full potency.

Assume that there is a 0.25% degradation each month. This has been used as it is a low rate but still enough to show that a two year expiry date makes sense. The logic would be the same whatever the rate – just extended over a longer time if it were slower.

We have further assumed that there are steady storage conditions, and that the rate of degradation is the same every month. It is quite possible that neither of these is true. Most obviously if a package such as a sealed pot is opened or the product is removed from the controlled conditions of a warehouse to be kept on a bathroom shelf where it could be affected by humidity, heat and light. But there are many other possible reasons for this simplistic approach to fail – such as the breakdown products that accumulate affecting the rate of degradation. Or that earlier poor storage, even for a short period, could throw everything out.

After 24 months, a typical expiry period for products such as levothyroxine, it would still be within UK potency requirement at 94.17%. An extra month (from 24 to 25), one month beyond expiry date, would only drop to 93.93%.

However, you can see that three or four years make serious inroads into potency.

Month % of original potency

0 100.00%

1 99.75%

2 99.50%

3 99.25%

4 99.00%

5 98.76%

6 98.51%

7 98.26%

8 98.02%

9 97.77%

10 97.53%

11 97.28%

12 97.04%

13 96.80%

14 96.56%

15 96.31%

16 96.07%

17 95.83%

18 95.59%

19 95.36%

20 95.12%

21 94.88%

22 94.64%

23 94.41%

24 94.17%

25 93.93%

36 91.38%

48 88.68%

My summary is that we really do need to try to adhere to expiry dates. But a single extra month beyond expiry (as described) is unlikely to make a significant different in itself.

This is just an illustration. No real levothyroxine tablets will follow this exactly.

[tattybogle]

Thank you . x

I apply a similar philosophy to 'best before' dates in my fridge , and i'm still in possession of a tin of jolly green giant sweetcorn that we used to use as a kitchen doorstop in 1973... you never know , it might still be OK .... but i'm not brave enough to open it.

[jimh111]

There may be a special consideration for hormone medicines like thyroid hormones. We never really know what they degrade into (and I wouldn't understand the chemistry in any case). It's quite possible that T3 and T4 degrade into analogues, molecules similar to the original hormone but not quite the same. This opens up the possibility that they could act as endocrine disrupting chemicals (EDCs). EDCs can have varying disrupting effects such as e.g. binding to receptors and so blocking T3 binding.

As far as I know the manufacturers check their medicines by seeing how much T3 or T4 is left after a year or two. They don't seem to check what the missing T3 or T4 has turned into. I'm just speculating but I wonder if the reason we find some brands better than others is because it has better purity and is more stable. Certainly, when I have some old tablets that don't work quite so well I am unable to compensate by taking just a tiny bit more - it doesn't help, which suggests the problem isn't purely the loss of some of the hormone.

I guess the moral is to keep your tablets stored in a cool dry place. I put them in the refridgerator, I know the manufacturers suggest 15 centigrade or whatever but I suspect this is simply because they only tested at this temperature.

[Hidden in reply to jimh111]

Jim .. I don’t know whether you’re a spendthrift or a cynic - but I like you 🥣

[helvella Administrator in reply to jimh111]

There is some information about the many thyroid hormone related substances that can be found in levothyroxine tablets. (Possible liothyronine as well, not sure.)

The substances appear to depend, at least in part, on the excipients present. But being totally outside the pharmaceutical establishment, it is very hard to understand what substances are present in newly manufactured tablets, as against those which only appear in some tablets, and some time after manufacture. For example, the nearly pure levothyroxine sodium ingredient will have undergone some degradation between being manufactured and being used producing one lot of degradation products. With another lot post manufacture.

[janeroar in reply to jimh111]

Fridges are quite damp?

[helvella Administrator in reply to janeroar]

They are both damp and dry!

When you open the door, condensation almost invariably forms. But if you leave things inside for extended periods, they get dried out.

Both humidity and dryness affect levothyroxine - significantly.

The crystalline structure of levothyroxine changes as it goes from anhydrous, through monohydrate to pentahydrate - and back. (These are the well-known forms - they might be other in-between forms.) Possibly many times.

[jimh111 in reply to janeroar]

I've always kept the tablets on an upper shelf or in the egg box on the door as it's not so cold. The packet has never felt damp although you might get some dampness near the bottom of the 'fridge. Also, levothyroxine tablets and many liothyronine brands come in bubble packs which I assume keep the tablets perfectly dry. I find the 'fridge works and has a constant temperature, our kitchen can get cold and wet / dry so the 'fridge is better, other rooms can get a bit too warm.

[Hidden]

It’s a pity that Best Before and Use By dates aren’t applied to medicines. I don’t mind the Coroner knowing I’ve got hubby’s dodgy Amlodipine in my cupboard but I certainly mind the GP knowing that I still use Syrup of Figs.

[Mollyfan]

This is so interesting….. I found a couple of papers which give a little light ( I think!)

First, an analysis of levothyroxine looking at the narrow therapeutic index and how often drugs are recalled because they lose potency… and the effect of excipients

juniperpublishers.com/jetr/...

Second, a PhD paper looking at the degradation of T4 and production of derivatives, some of which are harmful.

cris.brighton.ac.uk/ws/port...

The second reference gives evidence of the effects of temperatures of 20,40 and 70 degrees C over up to 6 months.

Degradation at room temperature over time.

[helvella Administrator in reply to Mollyfan]

Thank you - those are good and interesting papers.

Thank you.

[Marymary7]

I once ran out of my HRT meds and took a loose random estradiol valerate pill from the bottom of my drawer. Boy did I regret it. I was so ill in a very short time that night I actually thought ' is this how dying feels?' My stomach was so painful I felt so very ill I burped up a vile metal taste too. I'd never do anything like that again. Just saying! It's also a hormone although I suppose a fake one. Happy new year all.....

[Timetraveler67]

I was out when my tablets were delivered so the driver dropped them in my window and they landed on my hot radiator they sat there till I returned home about 3 hours later , did they lose there potency ?

[helvella Administrator in reply to Timetraveler67]

Impossible to say. However, the real issue is when they are at high temperature for weeks and months.