Dose Confusion When Switching between Insulin Delivery Devices

Incident Description

A patient was switched from Humulin R 500 units/mL (regular insulin provided in a multidose vial and obtained through Health Canada’s Special Access Programme [SAP]) to Entuzity KwikPen 500 units/mL (regular insulin provided in a prefilled pen and obtained through the community pharmacy) when the latter became available on the Canadian market. When writing the prescription for the Entuzity KwikPen, the physician asked the patient what dose of Humulin R was being administered. The patient reported that the dose was measured as 30 units on the syringe.

The physician wrote the prescription for Entuzity KwikPen 30 units twice daily, and the patient then filled the prescription at the community pharmacy. The patient declined pharmacist counselling at the time the prescription was dispensed, indicating familiarity with the use of high-concentration regular insulin. However, after using the Entuzity KwikPen product for more than a week, the patient experienced hyperglycemia and had to be treated in hospital. After discharge, the patient returned to the community pharmacy to ask the pharmacist how the hyperglycemia could have occurred.

Background

Specially marked syringes are available for patients to measure the insulin dose when withdrawing solution from a vial; U-100 syringes are intended for use with 100 units/mL insulin solution and U-500 syringes for the 500 units/mL product. The calibration markings on each syringe will indicate the number of units of insulin being measured only if used with the corresponding concentration of insulin.

Several high-concentration insulin products are currently available in Canada (Table 1) and each product is marketed in its own prefilled injection delivery device (known as an insulin pen). At the time of this incident, the Humulin R 500 units/mL product was available in multi-dose vials through the SAP, but was discontinued by the manufacturer and replaced with the Entuzity KwikPen, a prefilled pen device containing regular insulin 500 units/mL.

Table 1. Prefilled injection delivery devices (insulin pens) for high-concentration insulin products currently available in Canada.

Discussion

In the incident described above, the patient returned to the pharmacy to ask whether the community pharmacist could determine and explain why hyperglycemia occurred. After questioning the patient further about insulin use, the pharmacist identified that the patient had been withdrawing insulin from the Humulin R 500 units/mL vial using a U-100 syringe and measuring the dose to the 30-unit calibration marking. Therefore, the patient’s actual dose of insulin was 150 units. When the patient responded to the physician’s question about the dose of Humulin R 500 units/mL, the patient’s answer referred to the 30-unit marking on the U-100 syringe, not the actual insulin dose of 150 units. The patient experienced hyperglycemia because the 30-unit Entuzity KwikPen dose that the physician had prescribed was too low, as it was only one-fifth of the patient’s previous insulin dose.

Several factors contributed to the under-dosing error described in this bulletin:

• There was miscommunication regarding the patient’s insulin dose. Patients who are receiving insulin may only know their insulin dose by the unit markings on a syringe (if withdrawing from a vial) or by the number of clicks to be dialed (if using a pen device). These measurement indicators may not correspond to the actual number of units of insulin being administered. In this incident, failure to clarify the delivery device (i.e., the U-100 syringe) that the patient was using for the high-concentration product led to the prescribing, dispensing, and administration of an insulin dose that was one-fifth of the intended dose.
• Ideally, a patient who is withdrawing a dose from a vial containing 500 units/mL insulin solution would use a U-500 syringe, such that the syringe markings would accurately reflect the number of units being administered. In this incident, however, the patient had been measuring and administering the Humulin R 500 units/mL product with a U-100 syringe, possibly because U-100 syringes are more commonly available than U-500 syringes or because the patient was unaware of the existence of U-500 syringes. Consequently, when asked about the insulin dose, the patient would have had to perform a dose conversion calculation to correctly report the number of units of insulin measured in the U-100 syringe.
  The calibration markings on an insulin syringe will indicate the number of units of insulin being measured only if used with the corresponding concentration of insulin.

• High-concentration insulin products are not as commonly prescribed and dispensed as the standard-concentration products, resulting in a lack of familiarity by health care practitioners³ with the indications and/or doses of the high-concentration products. This knowledge gap may have contributed to the failure to recognize that the prescribed insulin dose with the Entuzity KwikPen was low. The most common reason for switching from 100 units/mL insulin to a high-concentration product is to enable a high dose to be delivered in a lower volume; however, 30 units is not considered a high dose and should therefore have been questioned at the time of prescribing and dispensing
• The patient’s vials of Humulin R 500 units/mL were ordered and received through the SAP. Under the SAP, the prescriber may order, receive, and store the medication, leaving the patient’s community pharmacy out of the communication loop.⁴ As a result, staff in the community pharmacy were not aware that the patient had been using Humulin R 500 units/mL. This communication gap can occur with any SAP product, and therefore the recommendations below may apply to all SAP products.
• The patient declined counselling by the community pharmacist because the change in delivery device was not recognized to be particularly significant, and the patient was comfortable with the use of high-concentration insulin. However, patient counselling, including demonstrating and confirming the appropriate use of an insulin delivery device, is an opportunity for pharmacy practitioners to help prevent dosing and administration errors. In this case, the opportunity was missed because the pharmacist was unaware that the patient was switching to a different insulin delivery device.

Recommendations

Prescribers

• Determine a patient’s insulin usage by confirming the type(s) of insulin, the concentration(s), the dose(s) in terms of units, and the delivery method or device used to administer each dose (i.e., syringe, insulin pen, or pump). Encourage patients to bring all of their medications to each appointment to confirm these details.
• Express the dose of insulin in terms of units both when communicating with patients and when writing prescriptions; this can only be done if the concentration of insulin and the delivery device have been confirmed.
• Develop a mechanism to communicate with the patient’s pharmacy about any medications for which prescribing or dispensing bypasses the patient’s pharmacy (e.g., SAP products, investigational drugs, prescriber samples).

Pharmacists and Pharmacy Technicians

• Ensure that standardized processes for collecting a patient’s best possible medication history include questions about medications that might bypass traditional pharmacy dispensing (e.g., SAP products, investigational drugs, prescriber samples).
• Before dispensing a prescription for insulin, confirm with the patient the type and concentration of insulin, the expected dose in terms of units, and the delivery method or device.
• Discuss with the patient every new or changed insulin prescription; emphasize that close monitoring of blood glucose is especially important when switching insulin products and that the primary care practitioner must be contacted if there is an unexpected result.

Health Canada

• Consider advising prescribers to inform the patient and the patient’s community pharmacy about any use of an SAP medication (e.g., on the form used for making an SAP request).

Conclusion

Dosing errors with high-concentration insulin products and related insulin delivery devices are preventable. All health care practitioners involved in prescribing, dispensing, monitoring, or providing education about insulin use should be aware of the need to determine the type and concentration of insulin, the insulin dose in terms of units, and the delivery device when communicating with and educating patients and others in the circle of care.