Special Alert! - Prepare for vials of neuromuscular blocking agents without cap warnings
Due to the increase in demand for neuromuscular blocking agents for critically ill COVID-19 (coronavirus) patients on ventilators, a drug shortage has occurred with certain products, including vecuronium and rocuronium (ASHP Drug Shortages List; FDA Drug Shortages). To assure continued availability of these two critically important drugs, the US Food and Drug Administration (FDA) has no objection to the request for the abbreviated new drug application (ANDA) holder, Gland Pharma Limited, to temporarily manufacture (June until July/August 2020) these drugs without the vial cap (seal) incorporating the usual statement, “Warning: Paralyzing Agent,” required by USP and FDA (Figure 1). Supply constraints prevent Gland 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 since the absence of the warning may make the vials look more like other medications in 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 will be safe handling, as noted below.
Gland produces vecuronium bromide injection (lyophilized powder) 10 mg per vial and 20 mg per vial for its marketing partner, Fresenius Kabi. The cap with the required warning statement and the temporary cap without the warning statement are pictured in Figure 1. These products will have the same US container and carton labels as before, with a paralyzing agent warning statement on them; only the vial caps will change. Vecuronium 10 mg vials are expected to arrive for distribution in mid-June; the date for distribution of the 20 mg vials has not been determined.
Gland Pharma also holds an ANDA for rocuronium bromide injection (50 mg per 5 mL, 100 mg per 10 mL) and provides this product to its marketing partners, Athenex Pharmaceutical Division and Almaject. Mylan Institutional LLC also has rocuronium injection that will be affected. The caps for these products will be temporarily manufactured without the usual statement, “Paralyzing Agent” (Figure 2). As with vecuronium, there is no change to the current US vial or carton labels. The date for distribution of the rocuronium products has not been determined.
These products are likely to be stocked in locations outside of intensive care units, including perioperative areas, emergency departments (EDs), and ambulatory surgery centers. So, it is important for hospitals and health systems to communicate the changes and prepare clinical staff wherever these products are stocked and/or used. Depending on the organization, these products may be found in crash carts; automated dispensing cabinets (ADCs); anesthesia carts, kits, and trays; and in other storage locations.
We highly recommend that organizations review measures for safe handling of neuromuscular blocking agents outlined in our June 16, 2016 article, Paralyzed by mistakes – Reassess the safety of neuromuscular blockers in your facility, as well as our Targeted Medication Safety Best Practices for Hospitals (#7). If these products reach your facility, we suggest immediately affixing an auxiliary label noting, “Warning: Paralyzing Agent,” to the vial caps. If not already in use, these labels can be purchased from your usual medical products supplier.
Please be prepared to have staff from the pharmacy or a medication safety officer visit various clinical locations in your facility or health system to work with practitioners in these locations to examine areas where these products might be stored, determine the likelihood of product confusion/mix-up, and act as necessary to store these products safely. Do not store vials in a way that only the caps are visible when looking down at them (Figure 3). Instead, be sure that vials are lying down so labels are visible in ADC drawers, anesthesia trays or drawers, or in other storage containers or shelving, particularly on low shelves in a refrigerator. Remind staff of the importance of barcode scanning prior to drug preparation and administration. Limit availability of neuromuscular blocking agents like vecuronium in ADCs to perioperative, labor and delivery, critical care, and ED settings; in these areas, store the drugs in a rapid sequence intubation (RSI) kit or lock-lidded ADC pockets/drawers. Take additional precautions, such as employing independent double checks, particularly when the ability to remove these drugs via override exists.