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k9diabetes
03-28-2008, 10:57 PM
I was reviewing a page on the U40/U100 conversion for posting to the main website and thought this was be a good time to go over the various terms used to describe insulin since the U40/U100 difference and the conversion to use U40 insulin in a U100 syringe has often been a subject of confusion. Eventually, this information will wind up on the main website.

Type of Insulin

Vetsulin = U40 = 40 international units of insulin in 1 mL of solution.

Novolin/Humulin NPH = U100 = 100 international units of insulin in 1 mL of solution

Filling a Syringe

Syringes are matched to the type of insulin used.

When you fill a U40 syringe with a U40 insulin, each mark on the syringe is 1 unit of insulin.

Fill the U40 syringe to the "10" mark with Vetsulin and you are injecting 10 units of insulin contained in 0.25 mLs of "insulin solution", which is insulin plus a diluent.

40u/mL divided by 4 = 10u/0.25mL

When you fill a U100 syringe with a U100 insulin, each mark on the syringe is 1 unit of insulin.

Fill the U100 syringe to the "10" mark with U100 NPH and you are injecting 10 units of insulin contained in 0.1 mLs of "insulin solution", which is insulin plus a diluent.

U100 insulin has less diluent added to it than U40 insulin so the solution is more concentrated.

Talking about Units versus Marks on a Syringe

When you match the insulin type and syringe type (U40 to U40 or U100 to U100), "marks on the syringe" and "units of insulin" or "dose of insulin" are the same thing.

10 marks on the syringe is 10 units of insulin.

It doesn't matter which insulin you are using, only that the syringe type and the insulin type are matched.

When you DO NOT match the insulin type to the syringe, "marks on the syringe" and "units of insulin" or "dose of insulin" ARE NOT THE SAME THING.

This typically comes up because there are times when it is useful to put U40 insulin in a U100 syringe.

When you do make the conversion, you...

Multiply the units of U40 insulin or dose of U40 insulin x 2.5 and

Fill the U100 syringe to mark on the syringe barrel that corresponds to the conversion.

So, for example, if your dog gets 10 units of Vetsulin per injection and you want to give that 10 units of Vetsulin in a U100 syringe, you...

Multiply 10 units x 2.5 = 25.

Then you fill the U100 syringe to the 25 mark to deliver 10 units of insulin.

Why It Matters

It is extremely important for anyone doing this conversion to understand how many "units of insulin" you are giving.

When you fill that U100 syringe to the 25 mark with Vetsulin, you are giving ONLY 10 UNITS of insulin.

Say your dog is rushed to the emergency room or you go to a new vet and they ask you how many units of insulin you are giving?

If you say 25 instead of 10, your dog is in serious jeopardy.

The emergency or new vet may not find out that there is a conversion factor involved.

So it's important to understand the difference between your dog's insulin dose (the number of units) and the strength of the solution of insulin and diluent your dog's insulin is.

While you can't really compare one insulin to another as dogs react to them all differently, a unit of one insulin is equivalent in terms of physical measurements in molecules to a unit of another type of insulin.

Natalie

k9diabetes
03-28-2008, 11:01 PM
Here is a link to a conversion table: http://felinediabetes.com/insulin-conversions.htm

We Hope
03-29-2008, 02:25 PM
Just going to add here that some other insulins are also U 100:

Humulin R/Novolin R= U 100 = 100 international units of insulin in 1 mL of solution

Humulin 70/30/Novolin 70/30= U 100 = 100 international units of insulin in 1 mL of solution

Levemir= U 100= 100 international units of insulin in 1 mL of solution.

Lantus= U 100 = 100 international units of insulin in 1 mL of solution

Humalog/Novolog/Apidra= U 100 = 100 international units of insulin in 1 mL of solution

There's also another U 40 commonly used, but mainly for cats:

PZIVet= U 40 = 40 international units of insulin in 1 mL of solution.

BTW--PZI Vet will be discontinued. Notice was made April 8, 2008:

http://www.idexx.com/animalhealth/pharmaceuticals/pzivet/index.jsp

IDEXX notice

http://web.archive.org/web/20070211093636/http://www.idexx.com/animalhealth/pharmaceuticals/pzivet/index.jsp

Link from IDEXX PZIVet pages February 2007--via Internet Archives. This page has now been replaced with the April 8, 2008 "Dear Doctor" letter; the old one can be read by using the link above.

"Proven stability for 3 years from date of manufacture"

http://www.vetsulin.com/PDF/Vetsulin_Dear_Doctor_Letter.pdf

Vetsulin is now FDA-approved for cats.

There are also some insulin strengths which can be obtained through a compounding pharmacy. The most common is U 40, but there is a U 50 strength available in beef insulin through a Texas compounding pharmacy, BCP:

http://www.bcpvetpharm.com/products_bovine.htm

"BCP PZI® insulin is available in 100u/ml 5ml or 10ml, 50u/ml 10ml & 40u/ml 10ml."

The compounding pharmacies are able to produce vials of just about any strength insulin required. This compounding pharmacy works with compounding human insulin for pets, but most compounded insulin is beef:

http://members.tripod.com/diabetics_world/pets.htm

Congaree Veterinary Pharmacy
1309-B State Street
Cayce, SC 29033
Toll free: 1-877-939-1335
Fax: 803-939-0073 803-939-1335

http://www.congareevetrx.com/

"PZI r-DNA human insulin. Their general order is for U100 strength in 5ml vials. Pharmacist Terry Fiffick says he has made strengths ranging from U2, U40, U50 and U100."

If you're using one of the not so common strengths of insulin, you'll need to ask your vet the type of syringe to be used with this special prescription.

k9diabetes
12-21-2008, 10:05 AM
After a handful of reports of dogs having problems recently with variations in blood sugar, I thought I'd bring up the possibility with any insulin that improper handling during extreme weather - hot or cold - can damage the insulin.

If you're suddenly experiencing regulation problems and you have changed to a new bottle of insulin, it's always worth considering that the insulin may be damaged.

We Hope
12-28-2008, 04:47 PM
http://www.auburn.edu/~deruija/insulin_preparations.pdf

This pdf has been around a while, but it's very good for explaining the differences in the various insulins--regular, NPH and the NPH/R pre-mixes, Protamine Zinc Insulin and the Lente family of insulins.

Regular insulins are on page 1, Protamine insulins are on page 2, and Lente ones are on page 3.

Kathy

We Hope
12-31-2008, 12:45 PM
Hi Marianne,

We've all had our turn at getting sick around here. Mine came last. :o

I know you're gonna start banging your head against the monitor when I say this, but it depends.

It depends on whether there's something else going on, such as an infection which may be causing this. In that case, you need to get that discovered and treated. If there is one, it can be the case for high bg's--it can also bring bg's lower than normal too--just as when you're sick you might be running a fever or you might be running a below normal temp. Either of them can be a sign of an infection.

People and animals with diabetes are prone to developing infections more so than those who don't have it. They tend to be things like UTIs and resps, for the most part. A lot of times these infections are subclinical or hidden, meaning you don't find a lot of evidence that they are there when you do tests--very true especially when it comes to UTIs. Many times, the only way to find the UTI and learn what antibiotic to give to get rid of it is learned by doing a culture. Sometimes the only hint they give you that there's something wrong is bg's that are too high or too low.

If there's no infection, there are possibilities that you can do some food tweaking to get rid of the higher bg's and you remember how you used to bring them down for Pebbles by taking her for a walk, since Dr. B. didn't believe in using R except for keto cases. Some doctors are very much against this and some aren't. I think some of it stems from a fear they may have that the used of some R will cause the animal to go hypo.

People on the other hand are told to use the fast or rapid acting insulins more liberally. They sometimes need to use them for "sick days" to bring down higher than normal bg's and if the person didn't calculate the fast or rapid acting used to cover meals correctly (he/she ate more than planned on), then people use some R as "corrective" insulin to get their bg's back in line again.

When you see R and NPH mixes like 70/30 and 50/50, the insulin is a pre-mix of R and NPH. 70/30 is 70% NPH and 30% R--50/50 is half NPH and half R. Not many animals need that much R as a rule, so when R is called for, it is usually much less than that.

If someone with diabetes needs to use cortisone-type meds for any reason, those can drive the bg's up and then there are times when some R is used to keep the bg's down while you're using the medication.

Organ damage can take place when you go high and stay there for a length of time. While we'd all like not to see any high bg's, going high and then coming back down within a reasonable period of time shouldn't affect anything. When the renal threshhold of 180 has been exceeded and the bg's have stayed there for a while are you going to get a positive reaction with the strips, because until that point, the glucose doesn't spill into the urine.

If someone's needing to use R, I believe you need to be blood testing and you need to be doing it more frequently than you might if there's no R in the picture. R works fast because there's no suspension to it. It leaves the system quickly because there's no suspension to it, but making a mistake with R can easily lead to a hypo incident.

Back in the old days when insulin was first isolated for use in controlling diabetes, R insulin was all there was. There were no suspended insulins until Hagedorn came up with PZI in 1936. Until then, if you needed to use insulin, you had to make sure you set an alarm to wake you up for a middle of the night shot. So the real diabetes pioneers used R all the time, each and every day for their total bg control.

This help any? :D

Kathy

http://tinypic.com/avj510.gif

Take a look at the time action profiles--the one for Humulin R, the one for NPH without any R added, and then look at the Humulin 70/30 which is 70% NPH and 30% R, then the Humulin 50/50 which is half NPH and half R. You'll see the type of "punch" R can pack when you compare that action profile to NPH alone.

We Hope
03-04-2009, 09:54 PM
http://www.noahcompendium.co.uk/Compendium/Overview/-21789.html

This contains all UK approved veterinary medications.

The ones which may be of most interest to this board would be:

http://www.noahcompendium.co.uk/Intervet_Schering-Plough/Caninsulin/-28705.html

Caninsulin information

http://www.noahcompendium.co.uk/Pfizer_Limited/Insuvet/-34411.html

Insuvet information

Just learned that Pfizer Animal Health purchased the Insuvet brand of insulins. Before the Intervet/Schering-Plough merger, Schering-Plough owned the Insuvet name, while Intervet produced Caninsulin/Vetsulin. To complete the merger, Schering-Plough agreed to sell the rights to the Insuvet line.

The Insuvet insulins were always produced by Wockhardt/CP Pharma, who has its line of Hypurin bovine and porcine insulins for people.

http://www.wockhardt.com/part_europe.html

"Schering-Plough--Insuvet contract manufacturing"

Since Wockhardt/CP Pharma is about the only one producing beef and pork insulins for humans, I'd believe that Pfizer has continued with this manufacturing agreement.

http://www.noahcompendium.co.uk/Dechra_Veterinary_Products/Vetoryl_10_mg_Hard_Capsules/-36945.html

Vetoryl (trilostane)--Dechra

Kathy

We Hope
03-27-2009, 11:34 AM
http://www.diabetes.org/for-parents-and-kids/diabetes-care/storage.jsp

American Diabetes Association

"Good insulin care begins with how the insulin is stored. Insulin does not work well when it's kept for too long or is exposed to extreme temperatures. If you buy several bottles of insulin at once, keep the unopened ones in your refrigerator. (Don't put them in the freezer. Insulin clumps at temperatures below 36ºF.) Before you open a new bottle, check the date printed on it. If it's past that date, don't use it -- it's too old.

"If your child uses up a whole bottle of insulin in a month or less, keep the bottle you're currently using at room temperature. It will stay fresh for up to a month without refrigeration, as long as its temperature stays under 86ºF. If you would rather keep all insulin in the refrigerator, warm up the insulin before injecting it. Cold insulin can make the shot uncomfortable. To warm it, draw up the right amount into the syringe, and then roll the syringe gently between your hands until it feels warm. Opened bottles of insulin will keep unrefrigerated for up to one month.

"When in doubt, always follow the insulin's manufacturer's storage instructions.

"Always check the insulin before you use it. Rapid- and short-acting insulin and glargine should look clear. There should be no cloudiness, little bits floating in the liquid, or change in color. Intermediate-acting insulin and ultralente should look cloudy, but you should not see any large clumps floating around. If you see any of these signs, throw the bottle away."

So you see you aren't harming the insulin if you normally keep it in the fridge and forget to put it back. It may not keep potency as long as a vial that's only unrefrigerated when in use, depending on how long it's been left out at room temperature. Intermediate-acting insulins are Lentes, NPHs and NPH/R mixes.

We Hope
05-18-2009, 12:29 PM
Outside of the analog insulins (Lantus, Levemir, Novolog, Apidra, Humalog), which are often very fragile, if insulin hasn't been exposed to any extremes either way (hot, cold or light), the opened insulin should be fine for 30 days at room temp.

Many people who know they'll use the entire vial within a month's time don't refrigerate their insulin after opening it at all, but keep it at room temp.

I don't think your forgetting the to put the insulin back in the fridge did it any harm at all--think that it was the wrong food with Buster. Now that you're back on the right food for him, you should see his bg's going down gradually within a few days.

http://care.diabetesjournals.org/cgi/reprint/26/9/2665.pdf

Diabetes Care-September 2003-Dr. Martin M. Grajower
How Long Should Insulin Be Used Once a Vial Is Started?

When he wrote this, you got plenty of responses from the human pharmas who make insulin--most of them pooh-poohing the idea that a vial could last more than 30 days.

http://care.diabetesjournals.org/cgi/content/full/26/9/2665?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=humalog+and+timing&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&sortspec=relevance&resourcetype=HWCIT

Diabetes Care 2003

http://care.diabetesjournals.org/cgi/content/full/27/5/1225

Diabetes Care 2004


Kathy

We Hope
06-16-2009, 03:39 PM
Dr. Grajower's article provoked a lot of responses! :)

http://care.diabetesjournals.org/content/27/5/1240.2.full

Response by Mark E. Moltich, MD

"However, I found the responses from Aventis, Eli Lilly, and Novo Nordisk to be totally unsatisfactory and self-serving.

"Although Aventis provides data showing stability for 4 weeks, it does not provide data showing that Lantus becomes unstable after that time. Lilly provides data to suggest that the amount of potency lost with an unknown type of insulin (probably regular) is negligible at 30 days even when stored at room temperature. However, they use the Committee for Proprietary Medicinal Products standard to say that a bottle can be open for only 28 days from a sterility perspective. So why does Lilly recommend discarding Humulin NPH, Humalog Mix 75/25, and Humulin 70/30 after shorter times? Where are the data to support these recommendations? Novo Nordisk provides no information regarding their vialed regular, NPH, 70/30, lente, or buffered regular preparations and only quotes the U.S. Pharmacopoeia, which itself provides no data. They then provide no data on NovoLog either, except to say that it should be discarded after 28 days. They also state that NovoLog used in pumps should be discarded after 48 h. Then follows a bewildering set of varying recommendations for different times for Novolog, Novolog 75/25 FlexPens, and Novolin N, R, and 70/30 InnoLet pens that ranges from 10 to 28 days. Where are the data?

"Without data showing that these insulins become unstable after specified periods of time or showing high contamination rates, the recommendations to discard the bottles and cartridges seem to be more based on a desire to sell more insulin rather than on facts related to safety and efficacy. Many of our patients use insulin doses <15 units/day and therefore would have to throw away bottles containing >50% of the original amount of insulin. At the current prices being charged by these manufacturers, this is a considerable loss of money on the patient’s part and a considerable excess profit for the manufacturers. The insulin-manufacturing community would do well to supply insulin vials in 5-ml amounts as well as 10-ml amounts."

http://care.diabetesjournals.org/content/27/5/1225.full

Insulin Storage in Europe, Drs. Gallo, et. al.

http://www.childrenwithdiabetes.com/dteam/2006-06/d_0d_e0a.htm

ChildrenWithDiabetes

Q:" have a question about Lantus. The literature with the bottle says an opened vial must be used within 28 days, whether refrigerated or not. Since the unopened bottle has an expiration date that's over a year away, why the 28 day limit once I open the vial?

"I use only nine units a day, so in a 28 day period that's 252 units. With 1000 units in a vial, I end up throwing away three-quarters of the medication. At $75 a vial, that's an expensive proposition."

A:"The drug companies make recommendations that allow for handling of the insulin under the worst case scenario. Insulin is a peptide hormone. It is broken down by light, extreme heat and cold, and by time. When the insulin is stored outside of the refrigerator, the shelf life is less than when it is stored in the refrigerator. Clinically, we ask patients to replace their insulin when they note blood sugars rising for an unexplained reason. You might try using your insulin longer with a careful eye towards making sure your sugars stay in control."

http://web.archive.org/web/20071224091405rn_1/www.uq.edu.au/ccah/index.html?page=43499&pid=0

And here we have Drs. Rand and Marshall from U-Queensland saying a 10ml vial of Lantus might be good for up to 6 months:

"Insulin glargine should be kept refrigerated to prolong its life.

"Insulin glargine has a shelf-life of 4 weeks once opened and kept at room temperature. Opened vials stored in the refrigerator can be used for up to 6 months."

We Hope
06-19-2009, 10:39 PM
http://www.globalrph.com/insulin_tables.htm

Global RPH-Pharmacokinetic profiles and Mixing Data

Jooniper
06-22-2009, 09:47 AM
Thank you guys so much for your replies! :) I'm learning so much!

Another question...

I dropped a brand new (only took 9 units out of it) 10mL bottle of vetsulin on the floor this morning. :( The bottle didn't break, and there were bubbles in it when I picked it up. Can I still use it? or do I toss it? I really hate to waste $40! One website I read this morning said it was ok if you let it settle again (letting the air escape the solution) but because of the slow release mechanism I'm not sure if it would still be ok to use. Link to website. (http://answers.1800petmeds.com/answers/1800/product/prod10764/questions.htm?scrollToTop=true)

BTW, I was rolling it when it dropped (so I hadn't pulled out this morning's dosage) and was really glad that I still had some left in an older bottle in the fridge. Thanks to the board I knew to keep extra on hand! :) THANK YOU!

I will have hubby pick up a new bottle on his way home from work just encase its not a good idea to keep using it. :) I'm also going to put a call into the vet and ask.

Thanks guys!

We Hope
06-22-2009, 10:08 AM
Jennifer,

As the site said, I think things will be fine but here's Intervet's toll free number. There's someone there who you can ask:

800-224-5318 Companion Animal (Dogs, Cats, Horses)
Normal business hours are 8:30 am to 5:00 pm EST.

http://www.vetsulin.com/dog-owner/faq.aspx

This page covers freezing insulin and leaving it out of the fridge; you might suggest they include information about a dropped, unbroken vial in these FAQ's.

Kathy

Jooniper
06-22-2009, 10:23 AM
Thanks Kathy :) I just called and left a message for the Vetsulin people. Thanks for the phone number. :) I will post what they say.

Jennifer

Jooniper
06-22-2009, 12:58 PM
I just got the phone call from Intervet and Kristine said that dropping it once shouldn't hurt it, to make sure there are no bubbles before injection, and as long as the bottle wasn't damage the product should work like its supposed to. She was super nice and very helpful.

Thanks Kathy! :D