Shelf life of Synthroid
Elizabeth
I just started a new dose of Synthroid (62.5 mcg, up from 50, TSH was down
to 1.7, fT4 was low mid-range). The doc did me a favor by giving me a free
one-month supply from her stash of sample packs. But now I wonder if it
really was a favor. The expiration date is 10/2008 -- still supposedly OK
but getting close. I've been on it for a week, and I feel worse instead of
better. I know it's too soon to tell, but I wonder if the stuff has lost
some potency. Granted, I've always felt worse right after an increase, so
maybe I just need to be patient.
Anyone experience feeling worse right after an increase? Someone here
mentioned the "J-curve" -- is that something that generally seems to happen
when first starting, or when increasing too?
Thanks,
Elizabeth
Alan B. Mac Farlane
or snake venom or things you have to keep in the fridge.
In feeling worse, maybe you are over dosing.
Maybe your Defense Structure is making this up for you.
Depression is the DS trying to make the person cry.
Go squeeze the psychophysiology, wring out the bitter salty tears, and the
depression goes away. Since there are no more emotional issues of the
Defense Structure to heal, the DS stops creating casualities, saddness and
regrets ...
This is a simple process to get out in front of the DS, but it hurts like
hell ... so most people are not want to do it.
You are the best person to Dx you on this one ... IMO and all that rot.
sumbuddie wear blind sea
:)
in article NoCdnVNohvuxbtrV...@earthlink.com, Elizabeth at
esni...@earthlink.net wrote on 6/5/08 7:08 AM:
kgrh...@alum.mit.edu
Shelf life of synth-T4 preps is well over a year PROVIDED they are
stored
properly -- NO exposure tohigh humidity NO exposure to elevated
temperature. Expiry dates for drugs are usually one year out -- so
IF the stuff was stored properly (including not being left in the drug
co
rep's car baking in the sun) THEN it should be OK.
As for the J-curve -- I believe I mentioned that. We have noticed
that
ANY dose change -- up or down -- seems to bring a short period of
feeling worse.
Sincerely
Kevin
willbill
> Dearest El-za-beth ... it has a long shelf life ... this is not like insulin
the question that is open to me is: to what
extent does toxic action move in with age of
synthetic T4 preps?
my own hunch is that it is not an issue
but i'm not sure about that. whereas with
the old insulins, i know it is not an issue
to the best of my knowledge, with the old insulins
(beef/pork/human), toxic action (with long age
beyond the "official expire date") is so minor
that it is not an issue
there are now 5 new analog synthetic insulins
(patents and profits seem to be the driver coz
otherwise they haven't offered anything much
to real diabetics (type-1 or type-2), and most
of them are suspect on longevity, as well as
open to the question of toxicity when they are
beyond the expire date
fwiw, synthetic "human" insulin lasts close to
100 years with good refrigeration and only
5% potency loss (same is true for pork and beef)
the most robust insuin is "fast" R(egular) insulin
(a.k.a.: neutral/soluble; see Actrapid below)
Jens Brange's '87 "Galenics of Insulin" has Table
16/p.59 time of storage of insulin preparations at
various temperatures until biological potency is reduced
by 2% and 5% respectively
^^^^^^^^^^^^^^^^^^^^^^^^
i believe that these are all (?) "human" insulins as beef and pork
appear (to me) to be either named directly or ref'd as "monocomponent"
(if i'm wrong about this, chances are someone will say so. :))
another question is what brands were used for the SL and L and UL?
afaik, Actrapid and Rapitard are Novo. one other point worth
mentioning is that prior to '87 Novo's "human" insulin was
semi-synthetic and not rDNA
Insulin-prep 4° C 15° C 25° C 40° C
Actrapid 36 / 92 yrs 5 / 13 yrs 12 / 31 months 5 / 14 weeks
Semilente 45 / 115 yrs 4 / 11 yrs 7 / 18 months 2 / 5 weeks
Lente 36 / 91 yrs 3 / 9 yrs 5 / 14 months 1 / 4 weeks
Rapitard 22 / 55 yrs 3 / 8 yrs 7 / 17 months 3 / 7 weeks
Ultralente 19 / 48 yrs 2 / 5 yrs 4 / 10 months 1 / 3 weeks
bill
Jessica
Hi Elizabeth,
My Synthroid has been raised two times since I was diagnosed in
January. Each time it is raised I feel sick(er) for a couple of days,
but eventually it wears off. Hope you're feeling better by now!
Jessica
Herman Family
"Jessica" <Jessica...@gmail.com> wrote in message
news:704255a9-7b81-46ec...@a70g2000hsh.googlegroups.com...
Elizabeth,
At the expiration date, the medication still has about 90 to
95 percent of its indicated strength. When it is brand new,
it is a little over 100 percent of its indicated strength.
Michael
Elizabeth
news:NoCdnVNohvuxbtrV...@earthlink.com...
Hi everyone,
I wanted to follow up on this post because perhaps my hunch was correct.
Because my numbers are now supposedly optimal, I was told to stay at my
current dosage. My sample pack had run out, so I was given a fresh
prescription. Lo and behold, about 8-9 days after starting the new
prescription, I feel markedly better. The whole 6 weeks I was on the old
sample pack, which was supposedly the very same brand and dosage, I felt
worse than previously, even though it was a slightly higher dosage than
before. As with everything, one wonders if there is some kind of
psychosomatic-placebo effect going on, but it wasn't until I counted days on
my calendar that I realized that something is indeed different with the
fresh medication. As Michael indicated, 5-10% of the potency might be lost
by the expiration date. Perhaps that 5-10% was critical for me.
Hmm.
Elizabeth
Rod
The official figures (both US and UK now, I believe) are that the
tablets should be between 95 and 105% of stated dose. The imposition of
this requirement appears to have shortened declared shelf lives/expiry
dates.
There is also the issue of storage conditions. In the UK by far the
majority of thyroxine comes in blister packs; in the US some?/most?
comes in bottles. The article referred to below considers some aspects
of their storage, specifically refrigeration. (In Australia, but the
idea is the same. :-) ) I think the company's response is of particular
interest. This is just a snippet from that response - much more at that URL:
"For Oroxine and Eutroxsig, the new stability data showed a loss of up
to 10% of thyroxine sodium in the first 6 months when stored below 25°C,
with some plateauing thereafter. As an interim measure, Sigma, in
agreement with the Therapeutic Goods Administration (TGA), decided to
immediately reduce the shelf life from 24 to 12 months (“store below
25°C”) and set the lower release to 98.0% (up from 92.5%), while
investigating reasons behind the loss in potency."
<http://www.mja.com.au/public/issues/182_12_200605/letters_200605-1.html>
On at least some tablets, they state a maximum temperature of 25C.
(There is a US standard as to what that means and some allowance is made
for transient over-temperature storage.) But I am certain that many
pharmacies (in the UK, at least) do not ensure that their facilities are
maintained at or below 25C at all times, nor will many have any form
of recording apparatus to allow proof of the conditions.
For what its worth, I think your hunch could well be spot on. Stuff the
"psychosomatic-placebo effect"; it was real.
The most important part of your post "I feel markedly better". Good.
Long may it continue.
--
Rod
Hypothyroidism is a seriously debilitating condition with an insidious
onset.
Although common it frequently goes undiagnosed.
<www.thyromind.info> <www.thyroiduk.org> <www.altsupportthyroid.org>
Dee
thyroid medications are heat, light and moisture-sensitive, too. Right now
I'm keeping mine in a cool, unlit location, until the summer temps cool off
a bit. Then I'll keep them in a different room, probably.
Anyway, your doctor may have stored them incorrectly? Or, they were just
plain old. ; )
Dee
"Elizabeth" <esni...@earthlink.net> wrote in message
news:u8CdnRLOQPquQBTV...@earthlink.com...
kgrh...@alum.mit.edu
> Elizabeth wrote:
> > "Elizabeth" <esniv...@earthlink.net> wrote in message
> >news:NoCdnVNohvuxbtrV...@earthlink.com...
> >> Hi all,
>
> For what its worth, I think your hunch could well be spot on. Stuff the
> "psychosomatic-placebo effect"; it was real.
>
> The most important part of your post "I feel markedly better". Good.
> Long may it continue.
>
> --
> Rod
>
> Hypothyroidism is a seriously debilitating condition with an insidious
> onset.
> Although common it frequently goes undiagnosed.
> <www.thyromind.info> <www.thyroiduk.org> <www.altsupportthyroid.org>
Strongly seconded, the "psychosomatic" label seems to get applied to
anything that the MDs can't figure out when there are no visible
problems. Way overused. Let's NOT starting applying it to ourselves.
As for synth-T4 shelf life, the key point is the temperature history,
as was pointed out in the good-stuff-snipped from above. Like
a carton of milk, let it sit on the counter for a few hours on a hot
summer's day and .... T3 and T4 are fragile biomolecules, easily
trashed by overcooking or bacterial or mold activity.
If you think about thyroid meds like milk or eggs and treat them
similarly, they will last longer. Too bad that this seems beyond
so many "trained professionals", like MDs and many pharmacists.
Then the stuff gets shipped by people with no idea what they're
carrying ...
HTH
Kevin
Rod
<>
> As for synth-T4 shelf life, the key point is the temperature history,
> as was pointed out in the good-stuff-snipped from above. Like
> a carton of milk, let it sit on the counter for a few hours on a hot
> summer's day and .... T3 and T4 are fragile biomolecules, easily
> trashed by overcooking or bacterial or mold activity.
>
> If you think about thyroid meds like milk or eggs and treat them
> similarly, they will last longer. Too bad that this seems beyond
> so many "trained professionals", like MDs and many pharmacists.
> Then the stuff gets shipped by people with no idea what they're
> carrying ...
>
There is something weird though. The original extraction of what was
later named thyroxine was done by boiling thyroids, first in an acid
(can't remember which one) and later in Sodium hydroxide or Barium
hydroxide - for up to 18 hours. Hardly the sort of treatment that marks
out pure thyroxine as being fragile!
Kendall's paper is here:
<http://www.jbc.org/cgi/reprint/72/1/213.pdf>
But when compounded into a tablet, it becomes a delicate little flower.
Seems crazy that a carefully crafted tablet is worse (in this regard)
than the bucket chemistry/biology of the original work!
The following paper makes some positive suggestions. (I think Levothroid
from Forrest does contain Calcium phosphate dibasic - not certain of
brand. And Berlthyrox contains Natriumhydroxid.)
=====
The effect of excipients on the stability of levothyroxine sodium
pentahydrate tablets
Himanshu PatelE-mail The Corresponding Author, a, Apryll StalcupE-mail
The Corresponding Author, b, Richard DansereauE-mail The Corresponding
Author, a and Adel SakrCorresponding Author Contact Information, E-mail
The Corresponding Author, a
a College of Pharmacy, University of Cincinnati, 3223 Eden Ave.,
Cincinnati, OH 45219, USA
b Department of Chemistry, University of Cincinnati, P.O. Box 210172,
Cincinnati, OH 45221, USA
Received 10 February 2003;
revised 8 July 2003;
accepted 8 July 2003. ;
Available online 23 August 2003.
Abstract
Levothyroxine tablets, 50 ?g, have been marketed for many decades but
have had numerous recalls due to degradation and failure to meet
potency. These experiments were devised to study the effects of various
excipients on the stability of levothyroxine sodium pentahydrate in
aqueous slurries and in formulated tablets. The active alone was found
to be stable in the solid state for 6 months at 40 °C/75% RH whether
stored in open or closed containers, and was found to be non-hygroscopic
under normal processing conditions (>30% RH). In aqueous slurries with
an excipient, the stability of the active improved as the pH of the
slurry was increased from pH 3 to 11. Tablets manufactured with lactose
anhydrous, starch, or microcrystalline cellulose failed to meet USP
assay requirements at 3 months at 40 °C/75% RH. Tablets manufactured
with dibasic calcium phosphate or mannitol met USP assay requirements at
3, but not 6 months when stored at 40 °C/75% RH. Tablets manufactured
with dibasic calcium phosphate and a basic pH modifier, such as sodium
carbonate, sodium bicarbonate, or magnesium oxide, met the USP assay
requirements at both 3 and 6 months. Thus, the use of basic pH modifiers
is a potential technique for improving the stability of levothyroxine
sodium pentahydrate tablets.
(Full URL with spaces added to allow breaks:
<http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T7W-49C5GG7-1&_
user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=
1&_urlVersion=0&_userid=10&md5=d205f932b79198d740c10ab5956acb33> )
Rod
acidification.
kgrh...@alum.mit.edu
> kgrho...@alum.mit.edu wrote:
>
> <>
>
> > As for synth-T4 shelf life, the key point is the temperature history,
> > as was pointed out in the good-stuff-snipped from above. Like
> > a carton of milk, let it sit on the counter for a few hours on a hot
> > summer's day and .... T3 and T4 are fragile biomolecules, easily
> > trashed by overcooking or bacterial or mold activity.
>
> > If you think about thyroid meds like milk or eggs and treat them
> > similarly, they will last longer. Too bad that this seems beyond
> > so many "trained professionals", like MDs and many pharmacists.
> > Then the stuff gets shipped by people with no idea what they're
> > carrying ...
>
> There is something weird though. The original extraction of what was
> later named thyroxine was done by boiling thyroids, first in an acid
> (can't remember which one) and later in Sodium hydroxide or Barium
> hydroxide - for up to 18 hours. Hardly the sort of treatment that marks
> out pure thyroxine as being fragile!
>
>
> Hypothyroidism is a seriously debilitating condition with an insidious
> onset.
> Although common it frequently goes undiagnosed.
> <www.thyromind.info> <www.thyroiduk.org> <www.altsupportthyroid.org>
Well, Armour has shown a shelf-life LONGER than 17 years in life
testing done
by (IIRC) US Army (whoever did it ended the test at 17 years) --
meanwhile
Thyrolar (tm), a synthetic T3/T4 prep in the same ratio as armour
needs
to be refrigerated to last for one year.
Certainly, the acidity/alkalinity and the presence or absence of
various
other substances has a humongous effect on the rate constants.
Temperature
and time are only the two most common variables in the equations.
However, for any rate constant or set thereof, the time/temperature
exposure will then control the decay of the active substance.
We have seen that synthetic thyroid preps appear, in general, to
have higher rates of decay than does armour.
So continuing the food analogy, armour is like peanut butter or
jelly, it can last fairly well on a cool shelf even without
refrigeration,
but synth-T4 pills are more like eggs or milk and go bad much
faster.
Perhaps we could entice deT, a real chemist, to weigh in on
this matter?
kgrh...@alum.mit.edu
Well call it "sodium hydroxide" in English (or "Natriumhydroxid"
auf Deutsch) I care not, it is still LYE.
<sarcasm> Sounds yummy! </sarcasm>
Elizabeth
Thank you for the research -- that is very interesting! I never would have
found that on my own. The only thing I wonder now is whether the expiration
date on the package of Synthroid indicates 3 months, 6 months, or a year
from manufacture. If it truly is one year, then I am now not so surprised of
its potentially lower efficacy.
Thanks again,
Elizabeth
"Rod" <poly...@ntlworld.com> wrote in message
news:6eueusF...@mid.individual.net...
Rod
<>
>
> Perhaps we could entice deT, a real chemist, to weigh in on
> this matter?
>
recently. Dare I suggest that I miss his joke postings? :-)
--
Herman Family
nearing the end of their life. The pharmacy has the fresh
stuff. Also, if you are in hot weather, you may notice that
the thyroxin loses potency within a month due to the heat.
Michael
deT notsuH
> kgrh...@alum.mit.edu wrote:
>> Perhaps we could entice deT, a real chemist, to weigh in on
>> this matter?
>
> It would be nice to hear from deT - he hasn't been around here much
> recently. Dare I suggest that I miss his joke postings? :-)
Dare to suggest it and it just might come true. NOOOOOOOOO!
Meanwhile, here's my two cents (scents? certainly not sense) on stability.
It isn't just temperature. I mean, you can actually measure a melting
point for T4 (around 150C ~ 300 F; can you say HOT HOT HOT?). But iodine
containing compounds are rather sensitive to redox conditions, and to light.
By that I mean that light can cause degradation (while this is totally off
the subject, but think about the silver in film, same idea once exposed to
light it changes chemical form). This is why the pills should come in those
ever-so-attractive orange or opaque bottles. Blister packs that samples
come in may not be as well shielded from light. Secondly, it is moisture.
Not that water and T4 don't mix, sure they do, but the integrity of the
tablets is subject to water. Good thing, too, or we'd never be able to
dissolve them in our tummies. But if the pill falls apart before its
time, the ingredients become more exposed to the air, and esp oxygen
(um, where the word oxidation comes from) that could chemically alter
the iodine in the T4 or T3 for that matter. The third ingredient is:
time.
My humble opinion is that T4 in Armour is no more nor no less stable than
the T4-only drugs out there. Sure, ingredients could make some of the T4
more susceptible to degradation within the given tablet. Synthroid was
famous for this by overstocking the T4 content in the beginning of its
shelf life, so that by the end of its shelf life it would still be within
"tolerance." I would note that that tolerance range has changed in part
due to that kind of manipulation. Prior to 2004, (I think, so don't quote
me), the tolerance range was + and - 10% of the stated dose. If you bought
100mcg Synthroid, it would have 110mcg at the beginning and 90mcg at the
end of its shelf life. In other words you might just as well have been on
112mcg dose and switched to the 88mcg dose (or vice versa if you caught
the last of a bottle and refilled from a new one). Hmm, does that spell
disaster? Oh, yeah. Current rules are + and - 5% of stated dose. The
FDA here in the US has challenged T4 makers to not only keep within those
bounds, but to be sure of their shelf life. This was part of the relicensing
process for T4 drugs. But some manufacturers are still struggling and
occasionally have their products pulled.
--
deT notsuH bass-ackwards ude.hcimu@pcird
"When putting it into memory, remember where you put it."