MHRA response re Liothyronine splitting v dissolving

[helvella]

Recently I wrote to the MHRA to ask the basis for the recommendation that liothyronine be dispersed/dissolved when a dose of less than one tablet is prescribed.

Today I have received their response. The entire text may be found below.

Thank you for your further request, made under the Freedom of Information (FOI) Act and dated 06 October 2018, where you asked to “know the basis of the decision that tablet splitting is not appropriate which would, of course, include data demonstrating unsatisfactory dosing in patients splitting tablets contrasted against satisfactory dosing in patients using the described dissolving technique.”

Ease of sub-division of tablets (“splitting”) is influenced by the size, shape and physical characteristics of the tablet. Tablets that are round in shape and have a relatively small diameter present significant challenges to uniform tablet sub-division. This is the case for liothyronine 20 microgram tablets marketed in the UK; all of which are round in shape and range between 5.5 - 6.0 mm in diameter. Further, attempts to sub-divide small tablets, such as liothyronine 20 microgram tablets, will present difficulties to patients or carers with limited manual dexterity.

Marketing authorisation holders that propose that a tablet should be sub-divided for purposes of dosing require to demonstrate compliance with the general test for uniformity of sub-division, included within the European Pharmacopeia monograph for Tablets (0478). This test method requires that a specified number of sub-divided tablet halves are weighed and that the uniformity of the individual weights (“uniformity of mass”) meets certain acceptance criteria. Data from clinical studies in humans for this purpose does not require to be presented; indeed such studies would be considered unethical as the content of drug substance in sub-divided tablets may be determined directly by analytical means.

However, for tablets containing a very low percentage of a potent active substance, assessment of uniformity of mass of sub-divided tablets is not considered to provide sufficient assurance of dose uniformity as while the weight of tablet halves may be uniform, the content of active substance within the tablet halves may vary significantly. This is the case for liothyronine 20 microgram tablets where the content of active substance is ~ 0.025% w/w of the tablet. For tablets containing a potent active substance, tablet crumbling / fragmenting as a result of tablet sub-division also presents an unacceptable risk of loss of active substance and surface contamination. The scientific literature contains a number of publications where difficulties with reproducible sub-division and poor dose uniformity have been highlighted when studying ease and uniformity of sub-division of tablets containing potent active substances.

To summarise, it is the view of the MHRA that tablet sub-division is inappropriate for tablet presentations of liothyronine 20 microgram tablets as accuracy of the dose is not adequately assured. This position has been strongly endorsed by experts of the Commission on Human Medicines (CHM) and its Expert Advisory Committee for Chemistry and Pharmacy Standards. The above forms the basis of the decision that tablet splitting is not appropriate for liothyronine tablets.

Liothyronine 20 microgram tablets may be dissolved in a glass of water. This ensures that the active substance is uniformly distributed in the volume of liquid in the glass. With the help of a measuring device, liothyronine may then be accurately dosed. This method of subdividing the dose by dissolving the tablets in water has been discussed with and endorsed by experts of the Commission on Human Medicines (CHM) and its Expert Advisory Committee for Chemistry and Pharmacy Standards.

If you are dissatisfied with the handling of your request, you have the right to ask for an internal review. Internal review requests should be submitted within two months of the date you receive this response and addressed to: [e-mail]. Alternatively, you may write to:

The Communications Division

10th Floor

10 South Colonnade

Canary Wharf

London E14 5AB

United Kingdom

The practice and clinical implications of tablet splitting in international health; Ivo Elliott et al; Volume 19 no 7 pp 754–760

onlinelibrary.wiley.com/doi...

The accuracy, precision and sustainability of different techniques for tablet subdivision: Breaking by hand and the use of tablet splitters or a kitchen knife; Diana Van Riet-Nales et al, Volume 466, Issues 1–2, 15 May 2014, Pages 44-51

sciencedirect.com/science/a...

Tablet splitting: a review of weight and content uniformity; MK Freeman et al; Consult Pharm. 2012 May;27(5):341-52. doi: 10.4140/TCP.n.2012.341.

[Abstract only available.]

researchgate.net/publicatio...

[I have just added links for the references indicated by the MHRA.]

[SlowDragon Ambassador]

So what do they actually recommend for the thousands of people taking 5mcg or 10mcg doses

Can you imagine if we all suddenly started using 3 tablets per day and chucking most away.....where.....down the sink ????

Great load of waffle and no action......yet again

Can not understand why 5mcg tablets of Liothyronine are not available

[Marz in reply to SlowDragon]

Bet they have a nice view from their office on the 10th Floor - and doing their best to hang onto it ...

[endomad in reply to SlowDragon]

LOL thats exactly what I said I am a water engineer and consider chucking hormones down the sink inappropriate as we already have too many hormones in our water supply.

I take 75mcg daily (25mcg at bedtime and 50mcg when i wake) so x by 90 days = 6750mcgs for 3 months, due to the water wastage i am prescribed 504x20mcg tablets for 90 days = 10080mcgs thats 3330 extra mcgs divide by 20mcg tablets = 166.5 extra tablets every 3 months.

I thought the nhs was short of money.

It actually works out well for me as my endo has been late a few times with my repeat prescription. Tbh i dont dissolve mine i just take 80mcgs a day and it still leaves me 144 spare tablets.

I am miffed to see them quote the EU directives when they do not use the EU directives on pricing and supply, if they did we wouldnt be in this mess with t3 prices.

I LMAO at this bit ' endorsed by experts of the Commission on Human Medicines (CHM) and its Expert Advisory Committee for Chemistry and Pharmacy Standards.' experts my arse, they just make this stuff up as they go along, we have been cutting tablets for years and 0.025% of tablet is the t3 jeeeeez bulk it out why dont you!!!

Absolute load of codswallop the whole reply.

[greygoose]

I notice that they did not address the subject of waste, nor of how to safely dispose of the solution remaining after the dose has been taken.

[SlowDragon Ambassador in reply to greygoose]

They haven't got a clue

[greygoose in reply to SlowDragon]

Probably not.

[crimple in reply to greygoose]

Yes GG but helvella did not ask about the waste!! So they are sticking strictly to the topic as you would expect from a bureaucracy! lol

[helvella Administrator in reply to crimple]

I did in my earlier contact which failed to produce the information I wanted - hence this request.

[endomad in reply to helvella]

You should send a copy and highlight that to the drinking water inspectorate dwi.gov.uk this is a list of water board directors,

instituteofwater.org.uk/boa...

None of the regional boards use reverse osmosis which is the only way of removing hormones and other pharmaceutical drugs from drinking water. One of the main reasons we have low fertility in UK is amount of female hormones in water, half the population are on contraceptive pill or HRT all which is flushed out in urine, into our water supply. Most common drugs are found in our drinking water supply especially antidepressants, not something the water boards like to talk about!

This is an old news report from 2 years ago but still relevant ref drugs in our water in the daily mail who have been water watch dogs for some time since the fluoride debacle

mailonsunday.co.uk/health/a...

It was taken from this university paper brunel.ac.uk/research/News-...

[Hennerton]

I despair. They have simply not thought through the implications of throwing most of the dose away, when taking a quarter at a time, as I and many others do. I was told it cannot be saved for a later dose by Mercury Pharma, so hundreds of pounds would be wasted every day and where does one dispose of it? Are you intending to follow up their reply? If so, could you please raise these points. I did to MP but have never received a reply and I lost the will to chase it up.

[helvella Administrator in reply to Hennerton]

I shall be taking this further but don't let that get in the way of anyone taking this information and using it to contact any appropriate organisations.

T'aint my information, t'is OURS.

[jimh111]

Thank-you for posting this. It's clear that the MHRA is aligned with the manufacturers. They do not mention why after decades they only now recommend dissolving tablets. It woud seem that liothyronine became soluble when the price rocketed! Whilst it is true the halves may not be equal they fail to take into account multiplle daily dosing of a drug with a 24 hour half life whhich mitigates any variations. They also do not consider that the patient may have a partially functioning thyroid, or be taking combined levothyroxine / liothyronine therapy. These will again substantially reduce the effect of any variations.

[Hypopotamus]

But isn't this the same people who tell us that we don't need Liothyronine anyway?

[helvella Administrator in reply to Hypopotamus]

No - so far as I am aware, the MHRA have never said that.

[Hypopotamus in reply to helvella]

I didn't mean the MHRA specifically Rob, but they are part of the of the DoH, as are NICE.

[helvella Administrator in reply to Hypopotamus]

Right - understand. I think we have to tackle each part separately.

[silverfox7]

Could this argument be used for any tablet we split though or are things like NDT mixed better? Or is this the only tablet that they have though of as it appears to be able to be dissolved. All sounds to be more cash orientated than health orientated. If health orientated then would/should any splitting be banned?

[helvella Administrator in reply to silverfox7]

They do specifically make this point:

for tablets containing a very low percentage of a potent active substance, ... This is the case for liothyronine 20 microgram tablets where the content of active substance is ~ 0.025% w/w of the tablet.

A desiccated thyroid tablet has a very much higher percentage of the named active ingredient. Therefore, even distribution might more readily be achieved.

Note this figure that is very easy to miss: 0.025%. Take a tablet. Divide it into 100 equal crumbs.

Take each crumb and divide it into 10 equal tiny sub-crumbs.

Then take each sub-crumb and divide in four.

That is how small an amount of active ingredient is present in thyroid hormone medicines. (Varies a bit, those which are larger tablets will be an even lower dose.)

[Hidden in reply to helvella]

If I have 5 minutes this afternoon I will try that.

[helvella Administrator]

Read what it says on the leaflet (there is an English translation available - somewhere).

If they say OK to split, then they must either be ignoring the arguments or have processes which ensure adequate distribution, etc.

[SlowDragon Ambassador]

Just looked up Liothyronine available in UK

bnf.nice.org.uk/medicinal-f...

Two things that are interesting

1) it's possible to get cytomel 5mcg from USA as a special. No price listed.

Anyone know what price is?

2) there are now 5 brands of T3 20mcg listed

New ones

AAH Parmaceuticals

Alliance Healthcare

Are these actually new brands? Anyone know?

[helvella Administrator in reply to SlowDragon]

AAH is part of the Celesio empire - which includes Lloyds (and former Sainsbury) pharmacies. In turn, part of the McKesson Corporation.

Alliance Healthcare is part of the Walgreen Boots Alliance empire.

AAH/Lloyds supply levothyroxine under their Northstar branding.

Alliance/Boots supply levothyroxine under their Almus branding.

The question seems to be, from which company are they sourcing their Liothyronine? One of the three we know? Or someone else?

Do bear in mind here that Celesio AG is the German parent of Celesio in the UK. Could that affect the decision as to which product should be supplied?

[SlowDragon Ambassador in reply to helvella]

Perhaps Celesio will be importing Thybon Henning and selling it on to NHS at nice profit?

[helvella Administrator in reply to helvella]

Reading the BNF page, I think that the BNF is simply identifying major distributors - some products vary in price depending on the distributor.

[jimh111 in reply to SlowDragon]

Looking at the NHS Prescription Cost Analysis nhsbsa.nhs.uk/prescription-... and doing some calculations Cytomel is about £4-97 per tablet and generic liothyronine 5 mcg about £4-29. So it is much cheaper to split 20 mcg tablets.

[helvella Administrator in reply to jimh111]

That might need re-assessment if you use the dissolving technique and throw away three-quarters of the product.

[SlowDragon Ambassador in reply to jimh111]

But 20mcg tablets are only cheaper if you are not throwing 3/4 of each tablet down the sink!!!

If they insisted on doing it that way.....my prescription would triple in cost to NHS and then 5mcg tablets would be much cheaper

Personally as I take a 20mcg tablet per day in 3 split doses, I am perfectly happy to carry on cutting it up with a scalpel.

It might be different, if you're taking 10mcg or 15mcg per day.

[jimh111 in reply to jimh111]

'So it is much cheaper to split 20 mcg tablets'

Split the tablets, don't dissolve them. The argument about the active ingredient not being uniformly distributed throughout the tablet is a red herring. It either has to be uniform or they have to inject 20 mcg into each tablet, I don't see that happening. It's true the dose will vary a little in split tablets but this is too small to be a practical problem. Our need for thyroid hormone varies during the day and T3 and T4 are pulsatile hormones, our levels naturally vary a little throughout the day.

Bear in mind that liothyronine is providing Total T3 and the body responds to the free component which is much smaller. Transport of T3 into cells, deiodinase of T4 to T3 and binding of T3 to receptors are all subject to various regulating factors. A small fluctuation in T3 during the day has no noticable effect. Carry on splitting your tablets and ignore these crooks.

[thyr01d in reply to jimh111]

But not when they have to be dissolved and the unused portion thrown away.

[jimh111 in reply to thyr01d]

Don't dissolve them, split them.

[thyr01d in reply to jimh111]

Ah Jim, I think you haven't read my other posts. I am prescribed two different brands of T3, one brand is splittable and I was given a special little box-cutter for this purpose. The other brand does not split properly and in the literature it says to dissolve if a smaller dose is needed.

If you know better, if you are an expert on this, please could you explain why you've told me not to do as instructed by the manufacturer?

[jimh111 in reply to thyr01d]

I have always split even if the tablet doesn't have a score line, just take a little extra care. I don't use a pill cutter I snap the tablet between my fingers and thumbs. If it won't split I use a sharp knife resting the tip on the table and gradually bringing the handle side down across the tablet. Crumbs can be picked up with a licked finger.

If you are taking a small amount of L-T3 say up to 10 mcg a day then you will be getting most of your T3 from your thyroid or from T4 in tablets. If you take more L-T3 then the effects of uneven splits will be relatively small.

At a worst care consider you split a tablet 60/40, into 12 and 8 mcg. After 12 hours there will be 70% of the extra 2 mcg left, i.e. 1.4 mcg to supplement the 8 mcg. So your dose will be 9.4 mcg instead of 10 mcg. This is well within the 90% - 110% tolerance required for manufacture of liothyronine tablets. In reality the effect is even less since you will also have 50% of yesterday's L-T4, so there is 14.4 instead of 15 mcg in your blood. We could then add 25% of the previous day's dose and so on. As you can see the real life variation is very small. Don't forget that you will also have the T3 coming from conversion of T4 in your blood. Conversion is to some extent varied according to fT3 and TSH levels which further smooths out any fluctuations.

The MHRA response is technically correct. It really matters in the case of very short acting drugs such as anaesthetics, it doesn't matter with drugs that have longer half lives. For patients who have difficulty remembering to take tablets endocrinologists sometimes recommend once weekly doosing of levothyroxine!

Liothyronine has been around for many decades. The advice to dissolve (and throw away) tablets has only been introduced in the UK since the price was hiked to astronomical levels. This advice has nothing to do with accurate dosing, it is purely to enhance profits.

We could look at the pharmacodynamics of liothyronine which further reduce the effects of minor variations in fT3 levels but I think I've gone into more than enough detail.

The introduction of instructions to dissolve and waste liothyronine is perhaps destined to be the second most successful marketing ploy. The greatest marketing gimmick was the addition of the words 'and repeat' to shampoo instructions. These two words induced many purchasers to wash their hair twice with a dramatic effect on sales.

[thyr01d in reply to jimh111]

Hi Jim, thanks for your reply and I know you are trying to help but you are not right. I am not prescribed T4, only T3 and my my thyroid is producing virtually nothing (TSH was over 95 which the Professor expert in this told me was coma level though the fact that I was on my feet meant my thyroid had managed to produce a tiny amount.)

I do not seem to convert, I had been on T4 for decades, and therefore cannot rely on T4 as a back-up.

There is no chance of snapping my pills with a finger and the cutter is specially shaped so that it is much better than a knife and catches all the crumbs but, as I said in my earlier post, one brand splits easily, the other does not because their shape is approaching spherical and they are very hard. The instructions state to dissolve not split.

Sorry if I sound irritated but I feel as if you are instructing me and also rather talking down to me in generalisations.

I asked if you were an expert and therefore knew something more than the rest of us who have genned up on all this because I don't want to mislead others by contradicting you if you are and if you know more. You haven't replied.

I was not requesting advice but intending to support Helvella in trying to find out whether there is any genuine reason for these instructions, rather than assuming that it is Big Pharma out to make more money.

[jimh111 in reply to thyr01d]

Sorry, there appears to be some confusion. I'm not an 'expert' whatever that means. I know liothyronine tablets have only to be within 90% - 110% of the stated dose and that patients report different properties of each brand, some being more effective than others. Indeed the manufacturers advise running blood tests and re-titrating each time you switch brands (as if the NHS would do this).

My comments were general, i.e. if you are on a low dose of liothyronine then the effects of uneven splitting would have a small contribution to overall hormone levels. On the other hand if the patient is taking large doses of liothyronine then the effect of an uneven split of a tablet would again be small. Essentially, a typical liothyronine dose for full replacement is 40 - 60 mcg. Thus, losing one or two microgram as the result of an uneven split will have negligable effect, especially when you take into account the hormone still in the system from previous days' doses.

I wasn't aware of spherical tablets, I've never seen them, they would be very difficult to split. If you are on liothyronine only then you will have less problems with splitting as you are not having to take small doses. How much liothyronine do you take? You can take it two or three times a day depending on which is most convenient. Remember T3 is a pulsatile hormone, the thyroid does not have steady secretion, T3 (and T4) are released in pulses.

There's no genuine reason for the suggestion to dissolve and throw away liothyronine. This requirement was invented after the price sky-rocketed.

[thyr01d in reply to jimh111]

In answer to your question Jim I am prescribed half of a 20 mcg tablet 3 to 4 times a day. I am fully aware that losing a small amount would not matter and that if one 'half' is smaller the next 'half' taken should make up for it, but, however much advice you offer the fact remains, that one brand of these tablets do not split successfully. Since I've told you that one brand splits normally and the other doesn't, I don't understand why you keep presenting information as if I don't know and it's not always correct, such as 'you can take it two or three times a day'. I don't think you are taking into account the effect of exercise. I didn't ask for instructions I made a comment relating to the originating post that I thought would be helpful. I have very strong feelings about people posting as if what they are stating is fact when it is just their understanding or their opinion. I think we need to be very careful not to think we know and not to mislead others based on our own experiences or understanding. It's so clearly a very complicated issue, it's very unlikely that any of us can state anything with certainty.

[jimh111 in reply to thyr01d]

I try to phrase my comments carefully as to whether they contain evidenced based fact, opinion or gueeswork. I often use phrases such as "I'm guessing", I tend to express less certainty than I have. Clearly the effects of splitting tablets doesn't matter in your case since you vary your daily dose by 33%. I'm aware of one UK brand that is difficult to split and commented that I find I am able to split (even these) tablets using a sharp knife in a tilting motion. This is just a tip for anyone else to try. The mathematics relating to uneven splitting and calculations based on pharmacokinetics are fact. These calculations show that the effects of uneven splitting is small. (We also know from studies that exercise has quite a small effect on thyroid hormone requirements).

There was no advice to dissolve liothyronine tablets ever since Pitt-Rivers discovered it in 1952. This advice to dissolve and throw away was introduced a couple (approx) of years ago by Concordia and later adopted by two other UK manufacturers. Liothyronine is barely soluble in water, 3.96 mg/L (or 3.96 mcg/mL) at 37 °C. School science shows us that solubility falls with temperature. The manufacturers recommend dissolving 20 mcg in 20 mL so there is little headroom. The manufacturers do not specify what temperature the water should be, it's only my guess but I doubt patients get sufficient solubility during the winter when water is around 5 °C. I doubt the manufacturers have conducted trials using cold water. This is my speculation, but I can't find any studies or reports from the manufacturers.

If liothyronine could be reliably dissolved in water the NHS would not pay £285 per vial of special soluble liothyronine for injection bnf.nice.org.uk/medicinal-f... . Liothyronine is barely soluble and requires special adjuncts to help it dissolve in water caymanchem.com/pdfs/16028.pdf . The recommendation to dissolve and throw away is a means of generating extra profits. Patients on these forums have been splitting liothyronine tablets for decades, our doctors have no problem with splitting tablets.

[crimple]

You are such a fount of knowledge Helvella. Thanks for the post.

[helvella Administrator in reply to crimple]

I'm OK with search engines.

[crimple in reply to helvella]

Yes they are brilliant but I could spend all day on them!

[Summer64]

I have to have 10 mcg per day so I cut mine in half. Does it really matter that much if I got a tiny bit more one day than the next? I make sure I use all the "crumbs". The instructions on mine from the doctor just say half a tablet daily. The only time I was told it may be better to dissolve was when I was on the Cynomel which is 25mcg per tablet instead of 20. If you did dissolve it I wonder if you can use the other half a day later.

[helvella Administrator in reply to Summer64]

Someone earlier on the thread said they had been told that they MUST NOT keep the liquid and use it later.

The description of how tiny the amount of active ingredient is (I posted earlier on this thread) means that it is theoretically possible for the active ingredient to be poorly distributed. (I suggest this depends on manufacturing technique. If liothyronine were fully dissolved in water (or, perhaps another liquid like alcohol), then that solution thoroughly mixed in, there would not be any individual particles or crystals that would distribute poorly. But I am no manufacturing pharmacist so this is just a thought experiment.

[thyr01d in reply to helvella]

Hello again Helvella, I did email the manufacturing company and ask them about not keeping the liquid and using it later but received no reply at all. I'm feeling mildy stressed and guilty being on here instead of working (self-employed) so won't chase the company up, but, if you have the energy and inclination it is TEVA UK Ltd (MA Holder whatever that means), Eastbourne BN22 9AG and the tables are Liothyronine sodium 20 microgram for oral use.

[helvella Administrator in reply to thyr01d]

MA Holder is manufacturing licence holder. (P/L is product licence holder.)

[Marz in reply to Summer64]

I read once that someone used to nibble on their T3 throughout the day - now that could be a way forward !

[helvella Administrator]

This is a link to an English version of the Thybon patient information:

dropbox.com/s/ccfr0tnmr7nom...

(Might be out of date, etc. - dated June 2017.)

It contains this sentence:

The tablets can be split into equal doses.

[silverfox7]

However we look at it though nothing is guaranteed. Yes, theory would would expect some mixing but you can't say with certainty that the amount you take has some T3 in it. The worse thing though is throwing away what you discard. It really is throwing money down the drain but we shouldn't be doing that either!

[Hidden]

Well,it has been an interesting coffee break helvella reading through this info and replies for sure!! - I have been splitting my MP Liothyronine in half for 4 years - 10 mcgs a day.

I achieved a state of relaxation, telling myself that over two days I will get the benefit of the whole 20mcg tablet,regardless of how accurate the split!!

Only last month told my GP that I wouldn't want to go back to how I was before being prescribed T3.

It is going to be an interesting visit to my Endo later this month, who prescribed it for me. Oh my word.......I can hardly wait !!! I will pass on any comments from him.

[endomad]

The french cynomel is scored into quarters to make halving/quartering easy, so one would assume it is reasonable to do so. Obvs the nhs t3 is a little tablet and by their own admission is only 0.025% t3 the rest are fillers.

[JGBH in reply to endomad]

The NHS T3 is pretty useless... would not want it to be honest.

[thyr01d in reply to JGBH]

Please JGBH, your post is so disheartening, could you explain? I could cry at the thought that what I'm taking (no T4 with it) could be useless.

[JGBH in reply to thyr01d]

Hello thyr01d,

Please please do not feel dishaeartened... don't forget we are all different and unique and react differently to different drugs... I expressed a personal opinion... all the feelers in T3... so it is not representative of how a "population of hypothyroid people" feel.

Very sorry to have caused you such distess even though inadvertently.

Please please just go by how YOU feel. It migh just be perfect or adequate for you. Keep a diary of how you feel and give it some time.

Keep positive and hopeful...

Very best wishes to you.

[thyr01d in reply to JGBH]

Thanks for your kind message, I will carry on with optimism!

[thyr01d]

I am given by the surgery two different brands of liothyronine, one brand does not say it cannot be split but the other does say NOT to split it. I have just noticed (very slow indeed) that when I take the brand that says to dissolve and not split, I seem to get steadily worse and worse. Could be imagined, but I think not and I think it's because I asked my Consultant if it would be okay to save half of the solution rather than throw it away and take it as my next dose. He thought it should be fine and that's what I've been doing.

Now I wonder if it becomes inactive if kept once dissolved - in which case I've been very silly because I've been dissolving two tablets, my full day's amount and drinking a quarter at a time, which means three-quarters may have been inactive.

I have started taking a whole tablet now, instead of half, and will see what happens. I am wishing I had not pointed out to the surgery that they are paying for 50% to go down the drain because I think I need the higher dose anyway and could have taken it without anyone becoming aware until afterwards, when I could say, if it were true, that I was much better on the higher dose.

Sorry for the ramble there, I got carried away!!! Thanks thyroid friends for 'listening'

[endomad in reply to thyr01d]

Also always checked the use by date before you accept your nhs t3, i have refused 2 batches as the date ran out before my 3 months prescription. They say its still active up to 6 months later but i would assume the effectiveness deteriorates. The nhs not only pay way too much but at my hospital seem to accept old stock close to use by date. I deff prefer the french cynomel and i can get away with 75mcg but 80-100 of nhs is still fine for me. x

[Zephyrbear]

I have been happily splitting my tablets for the last 7 years and feel perfectly fine on that, so I shall not be adopting that ridiculously wasteful practice any time soon!