PARALYZING AGENTS

Temporary caps lack crucial information

The COVID-19 pandemic increased the demand for neuromuscular blocking agents for critically ill patients requiring mechanical ventilation, leading to a shortage of the neuromuscular blocking agents vecuronium and rocuronium. To assure continued availability of these two critically important drugs, the FDA is permitting the temporary manufacture of these drugs without the vial cap (seal) incorporating the warning, "Paralyzing Agent," normally required by USP and the FDA (see photo below). Supply constraints prevented manufacturers from obtaining the products with the usual warning statements on the vial cap in time to address the shortage. This temporary situation has obvious safety implications because the absence of the warning may make the vials look more like other medications with similar size vials and cap colors.

Neuromuscular blocking agents are high-alert medications because of their well-documented history of causing catastrophic injuries or death when used in error. Staff awareness about the absence of the usual warning statement is critically important, as is safe handling.

The FDA has issued an alert to healthcare professionals about the temporary absence of the "paralyzing agent" warning statement embossed on the vial caps of vecuronium bromide for injection 10 mg per vial and 20 mg per vial, and rocuronium bromide injection 50 mg/5 mL, 100 mg/10 mL (see http://www.ismp.org/ext/497). These products are likely to be stocked in locations outside of the ICU, including perioperative areas, EDs, and ambulatory surgery centers, and in various storage sites, such as crash carts and automated dispensing cabinets. The Institute for Safe Medication Practices (ISMP) recommends that organizations stocking these products immediately affix an auxiliary label to the vial caps noting, "Warning: Paralyzing Agent," and urges organizations to review measures for safe handling of all neuromuscular blocking agents. ISMP also recommends that the pharmacy or a medication safety officer visit clinical locations to examine areas where these products might be stored, determine the likelihood of product confusion, and act as necessary to store these products safely. For example, to avoid visual confusion based on similar cap colors, vials should not be stored in a way that only the caps are visible to a clinician looking down at them.

COVID-19 PANDEMIC

Clinical trial changes dosing guidelines

An ICU hospitalist decided to order Actemra (tocilizumab) to treat a patient with confirmed COVID-19 and evidence of cytokine release syndrome. An interleukin-6 receptor antagonist, this drug is approved to treat adults and children age 2 and older with chimeric antigen receptor T cell-induced severe or life-threatening cytokine release syndrome. The drug, which has an anti-inflammatory effect, was undergoing a clinical trial for patients with COVID-19 and pneumonia, but it is not FDA-approved for this purpose. To assure that the hospital's infection prevention team would be consulted for these patients, Actemra was not included on the computer preference list for ICU hospitalists. If a hospitalist wanted to prescribe the drug, a workaround had to be established in which the hospitalist called the pharmacy to provide a verbal order. The pharmacist would then document the verbal order on a paper copy of the treatment guidelines and calculate a dose based on product labeling, which is 8 mg/kg for patients weighing 30 kg or more. For the patient in this case, who weighed 99.6 kg, the dose was 800 mg.

Unfortunately, the pharmacist did not realize that within the previous 24 hours, the hospital guidelines for the maximum allowable dose of Actemra had been changed electronically from 800 mg to 400 mg based on a new reference for treating patients with COVID-19. Consequently, the patient received a dose that was double the maximum dose under the new guidelines.

The patient was not harmed, but the event points out that, in any fast-changing situation, particularly during the COVID-19 crisis, paper guidelines may not be updated in a timely manner. Using an electronic resource is always preferable.