Letter to the Editor A Practical Guide to Concentrated Insulin for Pharmacists

We would like to respond to the insightful review by Andres and Clements that provides a detailed guide for the use of concentrated insulin, U-500 human regular insulin (U-500R), for pharmacists. Andres and Clements describe U-500R as being 5 times more potent than U-100 human regular insulin (U-100R). In the updated package insert (March 2013), U-500R is described as 5 times more concentrated than U-100R. This means that there are 500 units in 1 mL of U-500R and 100 units in 1 mL of U-100R. There is no difference in units between both types of insulin. Accordingly, ‘‘a unit is a unit’’ meaning an equipotent unit of U-500R is delivered in one-fifth the volume than those of U-100 insulins. This has been frequently misstated even in expert commentaries and is crucial for pharmacists and prescribers to understand. To be completely unambiguous, the prescribed dose of U-500R should always be expressed in the actual units of insulin and the syringe markings to be administered in accordance with the syringe type to be used. Specifically, when the patient uses a U-100 insulin syringe, he or she should be educated on how to draw up the appropriate number of ‘‘unit markings’’ on the syringe corresponding to the desired actual dose (ie, unit markings equal to onefifth the actual units). Similarly, when the patient uses a volumetric (tuberculin or allergy) syringe, he or she should be educated on drawing up the appropriate volume (mL) of U-500R to be administered (ie, volume markings in mL equal to 1/500th the actual units). The current package insert (2013) has a conversion table for both unit markings (U-100 syringe) and volume (tuberculin or allergy syringe) to assist in accurate dosing. Shortly after this information was added to the product label in 2011, the Institute for Safe Medication Practices published a summary of the label update, acknowledging that either syringe option could be used to administer U-500R. Critically, the patient should know his or her prescribed dose in actual units of U-500R, which syringe to use, and how to draw up the prescribed dose, which will allow the patient to communicate his or her U-500R dose accurately to a new health care provider in emergency department or hospital settings. For outpatient administration of U-500R, the use of U-100 insulin syringes has become the standard and most common practice. The U-500R vial (20 mL containing 10 000 units of insulin) has distinctive brown diagonal stripes, black lettering on white background with additional red lettering with warnings on the label, and a gray flip-top to distinguish it from U-100 vials (10 mL containing 1000 units of insulin or 3 mL containing 300 units). The authors of the review state that U-100R and U-500R have similar pharmacokinetic (PK) profiles and that the PK profile of U-500R is similar to that of an intermediateacting insulin such as neutral protamine Hagedorn (NPH) insulin. A euglycemic-clamp study by de la Pena et al describes a unique PK/pharmacodynamics (PD) profile for U-500R with prandial and basal activity while still showing similar overall insulin exposure (PK: area under the curve) and overall effect (PD: total glucose infused) to U-100R. Both formulations demonstrate expected dose-dependent PK/ PD characteristics. However, U-500R has a prolonged time to the maximal effect (6.4 hours vs 5.3 hours) and longer duration of activity (21.5 hours vs 18.3 hours) after a 100-unit injection versus U-100R. There are no data to suggest that U-500R is better absorbed than the U-100 formulation, and the extended duration of action of U-500R supports its use by multiple daily injections without concomitant use of U-100 insulins. There are special challenges with the use of U-500R in the hospital setting as noted in the Andres and Clements review. Samaan et al provide a template for U-500R hospital formulary policy with critical safety precautions and procedures to