Page 1 of 5 Last update 3/30/2010 Information supplied by Novo Nordisk Inc.
This document is intended for healthcare professionals practicing in the United States and may contain information that has not been approved by the FDA. It is supplied to you as a
professional courtesy in response to your specific unsolicited request. Novo Nordisk does not recommend use of its products in any manner other than as described in the prescribing information. Please refer to the full prescribing information for approved product labeling and important safety information.
Dilution of NovoLog®
Enclosed is information related to the dilution of NovoLog® (insulin aspart [rDNA origin] injection).
• Insulin Diluting Medium for NovoLog® is only intended for use with NovoLog® in sterile vials.
• Prior to use, Insulin Diluting Medium for NovoLog® should be stored at 2ºC - 8ºC (36º- 46ºF) and protected from light and heat until the expiration date; do not freeze. Once mixed with NovoLog® the sterile vial containing the mixture may be stored at temperatures below 30°C (86°F) for 28 days.
• NovoLog® maintained at least 96% potency at 7 days in an in vitro study that assessed diluted NovoLog® via continuous subcutaneous insulin infusion (CSII) with a NPH diluting medium.
• NovoLog® diluted with Insulin Diluting Medium for NovoLog® may not be the ideal choice for neonates with underdeveloped liver function. The decision to dilute with normal saline vs. insulin diluent should be made under the supervision of the treating physician.
Insulin Diluting Medium for NovoLog®
Insulin Diluting Medium for NovoLog® is designed for use by healthcare professionals for the dilution of NovoLog® for subcutaneous injection only; this diluent is not intended for use with any other insulin product. When diluting NovoLog® with Insulin Diluting Medium, the products should be combined in a sterile vial and the dilution should be performed under aseptic conditions. NovoLog® may be diluted with Insulin Diluting Medium for NovoLog® to a concentration equivalent to U-10 or U-50. Diluting one part NovoLog® to nine parts diluent will yield a
concentration one-tenth that of NovoLog® (equivalent to U-10). Diluting one part NovoLog® to one part diluent will yield a concentration one-half that of NovoLog® (equivalent to U-50).
Store unused vials of Insulin Diluting Medium for NovoLog® at 2ºC - 8ºC (36º- 46ºF) and protect from light and heat; do not freeze. Do not use the diluting medium if it does not appear clear and colorless, or if the cap is loose or missing. The diluted insulin preparation should not be mixed with other insulin preparations (i.e., NPH insulin) in the same syringe. The sterile vial containing the mixture of NovoLog® and Insulin Diluting Medium may remain at temperatures below 30°C (86°F) for 28 days.1 The components of the Insulin Diluting Medium and NovoLog® are provided in Tables 1 and 2 for your review.
Table 1. Diluent Ingredients
Product Diluting Medium for NovoLog®
Medium Water for injection
Buffering agent HCl and/or Sodium hydroxide (to adjust pH)
Preservative Metacresol, phenol
Other ingredients Glycerol, disodium phosphate dihydrate, water for injection to make 1 mL
Table 2. NovoLog® Components
Product NovoLog®
Insulin analog Insulin Aspart
Medium Water for injection
Buffering agent HCl and/or Sodium hydroxide (to adjust pH)
Preservative Metacresol, Phenol
Other ingredients Glycerin*, zinc, disodium hydrogen phosphate dihydrate, sodium chloride, water for injection to make 1 mL
*Glycerol=Glycerin
Dilution of NovoLog® in an Insulin Pump
As stated in the prescribing information,1 when used in an external subcutaneous insulin infusion pump, NovoLog® should not be mixed with any other insulin or diluent.
Novo Nordisk has not conducted clinical studies in humans evaluating the safety and efficacy of diluted NovoLog® in an insulin pump, and therefore, cannot recommend this practice.
Page 3 of 5 Information supplied by Novo Nordisk Inc
Jorgensen et al conducted an in vitro study that assessed diluted NovoLog® via CSII with a NPH diluting medium.2 The NPH diluting medium used in this study is no longer available; however, its ingredients and their concentrations are the same as the NovoLog® diluent currently
manufactured by Novo Nordisk.3 NovoLog® was diluted in concentrations of 10 U/mL and 50 U/mL and placed into 72 MiniMed 508 insulin pumps for 7 days at 98.6oF (37oC) with continuous oscillation. Two batches of each concentration and reference sample were tested for assay, degradation products (B28isoAsp, desamido insulin aspart and insulin aspart related impurities), high molecular weight proteins, macroscopy, pH, phenol and m-cresol. Statistical analysis showed no significant differences in degradation products between pump samples and reference samples. After 7 days, all pump samples and reference samples maintained at least 96% potency and none of the concentrations of preservatives, phenol and m-cresol, were below ~92% and ~88% of their original concentrations, respectively. In addition, macroscopy results and pH values were unaffected by in-pump-use testing. Storage of the diluted solutions for one month in sealed, sterile glass vials at 41 oF (5 oC) was shown to be acceptable.
Dilution of NovoLog® in Neonates
It is important to note that insulin diluent may not be the ideal choice for neonates since the preservatives in the diluent can cause toxicity in an underdeveloped liver.4 In such cases, use of normal saline solution without preservative has been studied in this population.5,6 If NovoLog® is diluted with normal saline for injection, the solution should be used promptly and should not be saved or stored, due to the lack of preservatives in the mixture. Stinging or burning at the site of injection may occur. No in vivo studies have been conducted with normal saline dilution of
NovoLog®; therefore, the appropriateness of the use of diluted insulin for an individual patient should be determined by the treating physician.
If you would like to order NovoLog® diluent, please contact Novo Nordisk at 1-800-727-6500. The above information is supplied to you as a professional service in response to your specific request. Novo Nordisk does not recommend the use of its products in any manner other than as described in the prescribing information.
About NovoLog®
NovoLog® was developed for use as a mealtime (bolus) insulin. As compared to regular human insulin (RHI), subcutaneous injection of NovoLog® provides a more rapid onset of action and a shorter duration of action. NovoLog® is indicated for the treatment of patients with diabetes mellitus, for the control of hyperglycemia. Having an onset of action within 10-20 minutes after subcutaneous injection, NovoLog® should be administered at the beginning of a meal. NovoLog® is normally used in regimens together with intermediate- or long-acting insulin. NovoLog® may be infused subcutaneously by external insulin pumps. NovoLog® may also be administered intravenously under proper medical supervision in a clinical setting for glycemic control. Hypoglycemia is the most common adverse effect of insulin therapy, including NovoLog®. Additional information can be obtained at the web address, novolog.com.
About Novo Nordisk
Novo Nordisk is a healthcare company and a world leader in diabetes care. In addition, Novo Nordisk has a leading position within areas such as hemostasis management, growth hormone therapy, and hormone replacement therapy. Novo Nordisk manufactures and markets
pharmaceutical products and services that make a significant difference to patients, the medical profession, and society.
Thank you for your interest in Novo Nordisk products. If you need any additional information, please do not hesitate to contact us at (800) 727-6500.
Page 5 of 5 Information supplied by Novo Nordisk Inc References
1. NovoLog® [package insert]. Princeton, NJ: Novo Nordisk Inc.; Mar 2010.
2. Jorgensen D, Solbeck H, Harboe E. Dilution of insulin aspart with NPH medium for small dose use in continuous subcutaneous insulin infusion does not affect in vitro stability. Diabetes. 2005; 54(suppl. 1):A102.
3. Data on file at Novo Nordisk Inc.
4. Thilo E, Rosenberg A. The Newborn Infant. In: Hay W, LM, Sondheimer J, Deterding R, eds. Current Diagnosis & Treatment In
Pediatrics. 18 The Mc Graw Hill Companies, Inc.; 2007:
5. Simeon PS. The premature infant with hyperglycemia: Use of continuous insulin infusions. The Journal of Perinatal and Neonatal
Nursing. 1992; 6(1):52-60.
6. Wintergerst KA, Hargadon S, Hsiang HY. Continuous subcutaneous insulin infusion in neonatal diabetes mellitus. Pediatr Diabetes. 2004; 5(4):202-206.
