We all know that unopened insulin must be kept in the refrigerator. But once in use, it can’t go back? The story of origin and quiet disappearance of a confusing guideline.
All manufacturers explicitly recommend to ‘Not refrigerate’ insulin pens in use. Why? It was kept in the fridge before, how can it hurt the insulin now that it’s open? Let’s imagine it was a hot summer day. Is it worse to put my insulin pen in the fridge or expose it to heat?
What is even more confusing, the guidelines start changing now! Let’s take a step back and look at the basics:
Storing insulin right
If you want to know what to do in order to keep your medication effective, just take a look at the package or the leaflet. Should it be in the fridge, is it sensitive to light, can it be at room temperature? For insulin in particular, there are two different situations: storing and in-use.
Before Opening: keep it in the fridge and it lasts until expiration date.
During Use: Once a vial, a cartridge or a new pen are used for the first time, the insulin can be kept at room temperature. But it needs to be used within a few weeks.
It makes sense: higher temperatures and an open product mean a shorter shelf life. Duh, we know this from our milk carton. But there is one more sentence on insulin pens packages, which has caused quite some confusion:
Pens in use — ‘Do not refrigerate.’
Guidelines, Labels and Leaflets
When a pharmaceutical manufacturer wants to bring a new product to market, they need to provide a huge amount of data. From clinical findings, proof of efficacy and safety, side effect warnings and dosing guidance down to storage recommendations.
For these, they do extended stability testing at different temperatures with their insulin pens, vials and so on, over months and years, to finally say: “If you follow this, your medication stays safe, effective and at optimal quality.” Great!
This info is publicly available at your national health authority’s website, eg FDA for the US and EMA for the EU. These authorities are not joking around, and if there’s changes to a label, there must be a reason for it! The first time ‘Do not refrigerate’ popped up was in 2003. Take Lilly’s Humalog for example, here’s the label from 14-years ago, with the new changes highlighted in green.
What happens if I refrigerate my insulin pen in-use?
Many would say from experience: nothing! Now, official medication labels are not famous for being very easy to read. The new guideline came without any explanations.
Many insulin users know from experience, that high temperature can lower the effectiveness of insulin. But why would returning insulin to the fridge hurt its potency, if it had been stored there for months prior? What is more, many users had been doing that for years without problems!
The confusion was considerably high. ‘Room temperature’ as in ‘up to 25°C/77°F’ may be easy to stick to in moderate climates. But what if you are in a place where ambient temperatures regularly exceed 86°F/30℃ ? One of our Australian users argued: I’d rather keep my pens in use in the fridge than having them in the summer heat.
Could open insulin be more sensitive to temperature fluctuations? But it says that open insulin vials are still fine refrigerated. So it seems unlikely that the guideline has anything to do with insulin quality. A community pharmacist wondered: Maybe it’s a ploy to help users not to forget an opened pen in the fridge.
Here’s what the companies say
Time to ask the authors themselves. Here’s the information we got, when calling the medical information hotlines of insulin manufacturers.
- Sanofi: This is a precaution, because patients were injecting cold insulin and reported side effects of the injection site.
- Lilly: When you return pen cartridges to the fridge from room temperature, air bubbles can form, which leads to injecting problems.
- Novo Nordisk: We are changing this guideline back for disposable pens.
When asked ‘what is worse: exposing insulin to heat (> 30°C/ 86°F) or putting in back in a fridge?’, all three sources agreed the fridge was the better option.
So the insulin itself is not affected by putting it back to the fridge! And this guideline exists only to prevent user mistakes?
Both injecting cold insulin and having air bubbles in the cartridge are of course inconvenient, but avoidable. Just remember to take insulin out of the fridge awhile before injecting and don’t store pens with needle attached. You could argue, that these are things most people with diabetes would know. Was this worth changing the guidelines?
Novo Nordisk’s answer was definitely a surprise. They actually had already been changing the labels. Checking FDA label for Fiasp, their newest additions to the market, it says disposable FlexTouch pens in use can be refrigerated.
The same goes for Novo Nordisk’s Tresiba. Down below is the original US FDA label from 2015 and ‘do not refrigerate’ disappeared in winter 2016. Within the last months, insulin labels have been updated with these new storage guidelines in both Europe and the US.
Happy now? No, wait a minute! So we established that keeping in-use insulin in the fridge is not affecting it’s quality.
Why does this guideline still exist for pen cartridges?
Novo’s medical information clarifies: ‘We wanted to allow refrigerator storage for insulin pens in-use again. However, pen cartridges were not cleared by the authorities, because many of the new pens have built-in digital functions, which can be affected by condensation in refrigerators.’
When asked what to do, if no other cooling option than a fridge is available, they also had a solution at hand: a zip lock bag to protect from moisture.
To learn more about MedAngel and find our online store, visit our home page.