Diabetic patients treated with insulin, whether for type 1 or type 2 diabetes, are prone to often unexplained swings in their blood glucose. These swings can vary from dangerously low to persistently high levels. Most diabetic patients, and most physicians, will adjust insulin regimens so as to avoid hypoglycemia at the expense of hyperglycemia. Among the “textbook” reasons for variable glucose responses to any given insulin regimen are…
1) site of administration, 2) exercise, 3) bottles not adequately mixed before drawing the insulin (for NPH, Lente, or Ultralente), and 4) duration of treatment with insulin (1).
The manufacturer, Aventis Pharmaceuticals, of the insulin Lantus (glargine) stresses that patients not use a started bottle of this insulin for >28 days (2). Two patients of mine highlighted this point.
L.K. is a 76-year-old woman with type 2 diabetes, diagnosed at 55 years of age, and treated with insulin since age 56. Her insulin regimen was changed to Lantus at night together with Novolog before meals. She monitors her blood glucose four times a day. She used a bottle of Lantus until it ran out; therefore, a bottle lasted for 2 months. Her recent HbA1c was 7.6%. I retrospectively analyzed her home glucose readings by averaging her fasting blood glucose levels for the first 15 days of a new bottle and the last 15 days of that same bottle. The results were 137 ± 20 and 187 ± 13 mg/dl, respectively.
E.T. is a 77-year-old man with type 1 diabetes since 29 years of age. His regimen was changed from Humulin N plus Lispro to Lantus at bedtime and Lispro before meals. He checks his blood glucose levels four times a day. He observed on his own that the last 25% of his Lantus bottle didn’t seem as potent as the first 75% and questioned me about this. I asked him how long a bottle of Lantus insulin lasts for him. He told me 40 days (consistent with his dose of 25 U/day). Simple math revealed that his last 25% was past the recommended 28 days.
I set out to review the available literature on insulin storage. Lilly recommends using an opened bottle of Humulin R for 4 weeks, Humalog for 4 weeks, and Humulin N for only 1 week, whether refrigerated or at room temperature. Humalog Mix 75/25, Humulin 70/30, and Humulin N cartridges can be used for 7-10 days (3). Novo Nordisk states that vials or cartridges of Novolog can be used for 28 days at room temperature but says nothing about how long it will last if refrigerated (4). In a private communication with a staff pharmacist at Novo Nordisk, I received the following message: “If human insulin vials that are stored under refrigeration are used beyond 30 days, the stability of human insulin vials is dependent upon a number of factors in addition to temperature [sic]. These factors include the number of injections per day, volume of insulin remaining in the vial, exposure to light, agitation, and technique used for dose preparation. The impact of these factors is difficult to measure and the health professional should advise patients on an individual basis concerning long-term storage of opened insulin vials when refrigerated.”
An exam review for pharmacists lists the expiration date for opened vials of Humalog as 4 weeks, but other vials of human insulin are listed as 30 days unrefrigerated and 3 months refrigerated. Cartridges of R and Lispro are listed as stable for 4 weeks and 70/30 or N for 1 week (5).
I dare say that most physicians are not aware of the potency of the various insulins once a cartridge or vial is opened. This is probably due to a combination of reasons: contradictory information in print (as illustrated above), lack of adequate dissemination of this information, and lack of real data on this subject.
Indeed, the comprehensive, well-written, and up-to-date American Association of Clinical Endocrinologists (AACE) Diabetes Guidelines do not refer to the issue of storage of an opened vial or cartridge at all, either as an issue for the physician to be aware of or as a point of discussion with patients as part of their self-management (6).
A search of the American Diabetes Association (ADA) website on the subject of storage revealed the following comment: “Although manufacturers recommend storing your insulin in the refrigerator, injecting cold insulin can sometimes make the injection more painful. To counter that, many providers recommend storing the bottle of insulin you are using at room temperature. Most believe that insulin kept at room temperature will last a month or so” (7).
The importance of not using bottles past their expiration date after opening is critical to good patient care. It is also an important cost issue. Many patients will be forced to throw out unfinished bottles of insulin. If the patient pays out-of-pocket, this increased cost could certainly spur the patient to continue using the bottle anyway, especially if he/she doesn’t monitor glucose levels on a regular basis and therefore doesn’t even see the difference between using a fresh or expired bottle. Do patients covered by prescription plans get enough insulin bottles to abide by the manufacturers’ recommendations or do they calculate the number of bottles required by how many units the patient takes on a daily basis?
Diabetes Care September 2003 vol. 26 no. 9 2665-2669
Weir G, O’Hare J: Insulin: therapy and its complications. In Principles and Practice of Endocrinology and Metabolism. 2nd ed. Becker K, Ed. Philadelphia, JB Lippincott, 1995
Aventis Pharmaceuticals: Lantus PI [package insert].
Novo Nordisk Pharmaceuticals: Novolog PI [package insert].
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