Why Not Continue to Refrigerate Open Insulin Pens?

I use both NovoLog FlexPens and Levemir FlexTouch pens, and something about the documentation I've read doesn't make sense to me. I know the pens should be refrigerated (but not frozen) before they are opened. That makes sense.

But the documentation for both seems to emphasize NOT storing either in the refrigerator when they are open and in use. I'm wondering why.

The documentation says they should be kept at temperatures BELOW 30°C (86°F) for up to a certain number of days (28 days for NovoLog and 40 for Levemir). But no indication is given for what temperature an opened pen should be kept above.

So why couldn't opened pens be continued to be stored at the same temperature they have been stored while they were open? Why does it make a difference after the pens are in use?

Insulin is a complex molecule. Not so much in the amount of amino acids but in its 3 dimensional structure. The binding between some acids might be at risk if the insulin is exposed to significant changes in temperature. These risks seem to be higher than the preservatory effects of storing the insulin at low temperatures. The manufacturer is cooling the insulin down after it has been produced. He knows exactly how many insulin molecules will degrade in this process. Thus he knows how many active units of insulin the vial will contain. You preserve this cooled state until you start a new vial. It will warm up to room temperature and in this process some molecules will degrade. This again is an effect the manufacturer has anticipated in its calculations. So the room temperature vial will be concentrated at 100U/ml at best. From this point the concentration of active molecules will slowly degrade. This again is a degradation the manufacturer is using in its calculation of the best before date. This process is slow enough to allow a significant span of days to reliably use the insulin (only true for glas vials not for most pump reservoirs). If you cool down the vial every day in the hope to prolong this time span you risk to degrade more insulin molecules in the cooling process. In other words: it is better to be exposed to a degradation that is well understood by the manufacturer. X days cooled, Y days opened, myriads of test runs to calculate the average degradation => confidence in a reliable product.

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In addition to whatever stress is introduced on the insulin by warming/cooling it multiple times daily, there is also the fact that some (many?) people find it uncomfortable to inject insulin which is still close to refrigerator temperature.

The use instructions which accompany insulin are probably alluding that at best there is no real benefit to continually cycling the temperature of the currently in use insulin vial/pen. And as was pointed out in the previous post, the worst case scenario is that you could actually be degrading the product.

-iJohn

As far as I can see, insulin is insulin regardless of the shape of the container. I keep all my insulin refrigerated all the time, and it's not unusual for a vial to last me 60 to 90 days. Until now (knock wood) I have not had a single one go bad. Not one. Not ever.

Just saying.

$0.02

My 2cents... If there was a good reason for this, I would be able to easily find it with a cursory search on the internet.

I have searched, and searched, and searched over the last two years since I started taking insulin, and have found nothing clear, unambiguous, and convincing. David's experience matches mine -- no problem refrigerating "opened" pens, vials. Insulin doesn't seem to degrade at all, when it would if I didn't refrigerate it.

From what I've been able to find on the subject I've concluded it is a (necessary) CYA policy by the FDA and manufacturers. Since insulin WILL degrade at higher temperatures and lose potency, and the general public (including diabetics) are not very reliable, counting on people to make sure they refrigerate insulin after they start using it and carrying it around with them through the day just isn't realistic.

So, they say once opened, keep at room temp and use it all before 30 days. That's a "catch-all" that keeps the lowest common denominator diabetic safe. As for the rest of us, I think we have enough andecdotal "evidence" from the actual D community to pretty much ignore that directive, and refrigerate it if we want to.

I keep mine in the fridge all the time too. Just the other day decided to keep one lantus and one novo out of the fridge because the fridge that was available is a junky old mini fridge that that makes a lot of weird noises and I was afraid might malfunction and freeze everything solid— but other than situations like that I keep them in the fridge all the time.

Because it stings even more if you inject cold insulin, especially in bigger amounts.
Have you ever injected fridge cold Insulin? yuck that is not nice… :(

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I don’t notice it

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The "big amounts" has a lot to do with it.

As a T2 with an early morning IC of 1:3 and an CF of 1:7, simply correcting a modest AM high and eating a small amount of carbs (15g) requires a sizable dose of insulin.

I can tell you from experience, when I was doing MDI, 10U of 35F insulin gets noticed!

To each his own. I don't notice it at all. And even were that not so, it's a trivial price to pay for getting 60 to 90 days from a vial. (Unless your insulin is free, which mine most emphatically is not.)

I do the same thing! And have never had insulin go bad....

I keep mine refrigerated (Humalog and Lantus) at all times and have never had a problem with it. I even inject while it's still cold (directly out of the fridge). No problems.

When I was younger I used to never refrigerate my insulin (Novolin N and Novolin R) at all. It was always at room temp. and even then I never had a vial go bad. But I was a rebel then and wasn't doing anything "by the book".

Thanks, Holger. Your explanation makes some sense to me.

Still, I don't understand why the manufacturer wouldn't list what exact temperature their opened insulin should be kept ABOVE, since they so clearly list what to keep it BELOW. We are told not to freeze the insulin, which of course we are already doing with the unopened stores insulin. But if freezing were the lower limit, then it wouldn't matter if the opened insulin was kept in the fridge where the unopened insulin can safely be kept.

It just bothers me, documentation-wise, to know the upper limit but not the lower limit of what temperatures it is safe to cycle opened insulin between. If the manufacturer has that info, why not state it in the specs?

I'm not suggesting that the time given by the manufacturer in which to use opened insulin is incorrect. The specs have the precise maximum number of days.

The argument that injecting colder insulin could be uncomfortable seems anecdotal at best and would probably be worded differently on the product specs.

In my opinion, the packaging, purity & composition of modern insulins result in it not making a significant difference whether or not you refrigerate the insulin or keep it at whatever room temperature may be for a period of a month or probably even (much?) longer.

There is going to be degradation over time either way. But neither approach will damage the insulin sufficiently to affect its suitability for its intended purpose.

Yes, I am persuaded by Holger's reasoning that temperature cycling the insulin is potentially more stressful than not refrigerating it. However, until someone can reference the results of some type of formal comparison study, it is only an argument, not proof.

It is even more the case that multiple anecdotal observations from people asserting "I keep it refrigerated except when I use it and it's been just fine!" are also not any kind of quantifiable proof.

All that means is that the insulin was ostensibly still "good enough". It does not provide any kind of a quantifiable measure of just how "good" the insulin may be compared to another method of short term storage.

It always amazes me to what extent people can work themselves up over how to store insulin.

-iJohn

Possibly the more it's refrigerated after starting use, the more consistent it's strength will be. Insulin can weaken after out of the fridge. It might not weaken drastically, but a bit. That's a good idea to keep it in the fridge whenever you're not on the go.

I've used all sorts of insulin, including in pens (both long short acting), and bottles. I've left them at room temps for MONTHS, and NEVER, in 35+ years of using insulin have I found a bottle or pen go bad, save ONE POSSIBLE BAD BOTTLE, which WASN'T due from being out of the fridge for too long--and even that POSSIBLE bad bottle may have been not bad after all and just my guess that it was bad as I was having a hard time with my bgs for a while so I threw out the bottle before it was empty. I understand mfgrs and doctors are super cautious about insulin and pill longevity (for potency) but in reality, I've had insulin work just fine many months after first use and at room temp. I've taking pills YEARS after expiration without issue. I know some of you will cringe and or argue with me. That's OK. I'm a pragmatist--if it works, I fine with my methods. cheers!

Yepper. Pretty much also my personal experience.

For some reason people seem to read a lot more into a date than it can actually mean. I've never understood why folks seem to think the modern insulins are so fragile. Yes, they are fragile. You definitely need to take appropriate storage cautions when using insulin. But it is not that fragile, at least not in terms of its fitness for its intended purpose. ;-)

OTOH, (Medtronic Enlite) glucose sensors I'm not so sure about. Those things are labeled as expiring 6 months after manufacture and I think they may actually go wonky that quickly. While I don't refrigerate them, if it's going to be more than a month before I expect to use them, I store them at a lower ambient temp "just in case". It's a combination of not having had that much experience using them and that the unit cost on those puppies is too high for me to be cavalier about their storage. Yet. Oh, well.

-iJohn

John, I agree with everything you wrote. I'm not going to order my next 90 day supply until I'm almost out of sensors which is a departure from how I order my sets. I always have plenty of sets and insulin on hand. I'm glad I now have central air to keep things cooler. :)

I understand that all of our experience, and the experience of others, may seem to point to different things. All of your supporting anecdotal experience around refrigerating—or not refrigerating—opened insulin is actually relieving to me. And it all seems perfectly valid from each of our separate points of view.

But my original question had to do with the documentation created by the manufacturer's of the products. My interest may stem from my profession of being a technical writer for almost two decades. I know that the manufacturers, as well as their legal and scientific teams, would NOT casually state or withhold information in the specs or the white papers for their products.

I just find it odd that there seems to be a rather glaring omission in the documentation (no ABOVE temperature stated for opened insulin) that makes this an open question that we can have differing opinions about.

I wish we could get in touch with an Eli Lilly or Novo Nordisk representative to hear their take.

If you ever get info straight from "the horse's mouth", I think it's safe to say many of us would like you to share here. Having said that, I'd still take what they say with a grain of salt. Just like MM reps and I argue about covering Enlite sensors with two overlapping IV3000 tapes. I do it and it works. they claim all sorts of bogus "reasons" (which make ZERO sense) why one shouldnt cover the Enlite sensor & transmitter with two overlapped IV3000. I don't think anyone here would believe me if I repeated what two of the MM reps told me. Both of their "reasons" are so ludicrous, a 12 year old would know better than to believe them. On sedond thought, here goes: "Don't cover the sensor and transmitter with Iv3000 because it interferes with the radio signal to the pump." Honest to god, I'm not making this stuff up.