FDA Advise-ERR: Reported Medication Errors with Veklury (Remdesivir) Emergency Use Authorization
On May 1, 2020, the US Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for use of the investigational drug, remdesivir, for treatment of patients hospitalized with severe 2019 coronavirus (COVID-19) disease. The EUA includes a Fact Sheet for Health Care Providers, which has been updated several times to provide new safety information, clarify dosing and administration recommendations, expand the indication for use, and include the proprietary name, VEKLURY.
Remdesivir is a direct-acting antiviral drug that inhibits viral RNA synthesis. It is an investigational drug and is not currently FDA-approved for any indication. Remdesivir is supplied in two formulations for intravenous (IV) administration:
remdesivir injection, 100 mg/20 mL (concentrated solution)
remdesivir for injection, 100 mg per vial (lyophilized powder)
Remdesivir injection (concentrated solution) contains twice as much of the solubilizing agent, sulfobutylether-β-cyclodextrin sodium salt, as remdesivir for injection (lyophilized powder) and should only be used in patients weighing 40 kg or more. Remdesivir for injection (lyophilized powder) is used in both adults and pediatric patients. The two formulations have different recommendations for storage, dose preparation, and administration.
Mandatory reporting of adverse drug events (including medication errors)
As part of the remdesivir EUA, the prescribing healthcare provider (or their designee) is required to report medication errors, serious adverse events, and deaths to FDA Medwatch within 7 calendar days from the onset of the event, as outlined in the Fact Sheet for Health Care Providers. FDA uses this information to determine if additional regulatory action is needed to address the reported events.
FDA has received numerous medication error reports related to incorrect preparation, administration, and storage of both remdesivir formulations (Table 1). The reported errors resulted in administration of the wrong dose or formulation, missed doses, or the need for pharmacy to discard vials or solutions that had been improperly prepared or stored. None of the reports described serious adverse patient outcomes related to the medication errors.
|Error type||Description of error|
|Wrong formulation||A child weighing less than 40 kg received one dose of remdesivir injection (concentrated solution) instead of the recommended lyophilized powder (remdesivir for injection)|
|Wrong preparation||Several doses of remdesivir for injection (lyophilized powder) were incorrectly reconstituted with 0.9% sodium chloride instead of the recommended sterile water for injection; the doses were also incorrectly diluted in 5% dextrose and water instead of the recommended 0.9% sodium chloride; the doses were not administered to patients|
|Incorrect storage||Vials of remdesivir injection (concentrated solution) were left out of the refrigerator overnight for more than 12 hours (sealed vials can only be stored up to 12 hours at room temperature prior to dilution) and had to be discarded|
Safe Practice Recommendations
Please consider the following recommendations to help prevent the types of remdesivir errors that have been reported to FDA:
Refer to the remdesivir EUA letter and Fact Sheet for Health Care Providers for details about remdesivir use. The Fact Sheet includes the full EUA prescribing information with complete dosage, administration, preparation, and storage instructions for safe and effective use.
Use standardized order sets to guide the selection of the appropriate formulation and to ensure it is specified within each order. For pediatric patients weighing 3.5 kg to less than 40 kg, ONLY use the remdesivir for injection (lyophilized powder). Remdesivir injection (concentrated solution) is ONLY for use in adults and pediatric patients who weigh 40 kg or more.
Provide those preparing remdesivir with clear, step-by-step instructions for reconstitution and dilution. Remdesivir for injection (lyophilized powder) is reconstituted with sterile water for injection. Both formulations need to be further diluted in 0.9% sodium chloride prior to infusion. The Fact Sheet for Health Care Providers contains different dilution instructions based on the remdesivir formulation and patient weight.
Ensure proper storage of each formulation prior to and after dilution. Unopened remdesivir for injection (lyophilized powder) vials can be stored at room temperature, whereas remdesivir injection (concentrated solution) vials should be stored at refrigerated temperature but must be brought to room temperature (up to 12 hours) prior to dilution. Once prepared, diluted remdesivir solutions can be stored up to 4 hours at room temperature or up to 24 hours refrigerated.
Consider utilizing alerts in computerized order entry systems and posting labels in storage areas to indicate that remdesivir injection (concentrated solution) is “ONLY for patients weighing 40 kg or more.” A hard stop that requires entry of the patient’s actual weight might be useful prior to prescribing the drug.
Ensure the one-time loading dose on day 1 is correctly documented so subsequent maintenance doses starting on day 2 are correctly timed.
Update order forms and electronic health systems to include both the proprietary name (Veklury) and generic name (remdesivir).
ISMP thanks Celeste Karpow, PharmD, MPH, FISMP, and LCDR Valerie Vaughan, PharmD, of the US Food and Drug Administration Division of Medication Error Prevention and Analysis (DMEPA), for providing this FDA Advise-ERR.