ISMP Alerts
Maria G. Tanzi, PharmD
Over the past few months the Institute for Safe Medication Practices (ISMP) has released information on a compounding error that occurred with the investigational use of remdesivir for the management of COVID-19 patients, the potential for overdoses with a 2% propofol product recently approved by FDA for emergency use, and updated vincristine labeling and packaging.
Remdesivir investigational labeling
In early May, FDA issued an emergency use authorization (EUA) for the investigational antiviral drug remdesivir for the treatment of suspected or laboratory-confirmed COVID-19 in adults and children hospitalized with severe disease. Since then, ISMP has received a report of a compounding error with remdesivir that was attributed, in part, to confusion around its labeling.
The hospital in which the error occurred stocked two different versions of remdesivir. One formulation was a lyophilized powder for injection, 100 mg, and the other was an injectable solution with an equivalent amount of drug.
The vials of lyophilized powder had a label listing the total amount (100 mg) of drug inside. But the vials of the injectable solution had a label that only listed 5 mg/mL and the total volume of 21.2 mL.
The adult protocol called for an initial loading dose of 200 mg, followed by subsequent 100-mg doses. However, a pharmacy technician used 2 vials of the injectable solution to not only prepare the loading doses (i.e., 200 mg), but also the subsequent doses (i.e., 200 mg/dose instead of 100 mg/dose).
The hospital noted that confusion with the labeling of the injectable solution vial, which does not include the total dose (100 mg) in the vial, played a role in the error. Confirmation bias also contributed when the pharmacist failed to catch the error during the verification process. The report noted that there was no barcode available to scan on the vials. Multiple patients received the 200-mg doses, but no adverse reactions have been reported to date.
To prevent this error, pharmacies should consider adding a printed barcode label to each remdesivir container to allow barcode scanning for product and dose verification. Another recommendation is to affix an auxiliary label to remdesivir injectable solution vials to note the total amount of drug (100 mg). Health care providers should also have information on this labeling issue.
“Investigational drug container labels do not follow the same standards as approved drugs,” Michael Cohen, RPh, MS, ScD (hon.), DPS (hon.), FASHP, and president of ISMP, told Pharmacy Today.
“Some containers do not even have labels at all, and others fail to provide recognizable strengths. They do not have bar codes. Many are from sponsors outside the United States. It’s an untenable situation, but one we have put up with for years. Who knows how many medication errors have happened as a result, or how this situation may have impacted drug research? It is time for a change.”
Cohen advocates for a change in the way investigational drug labeling is done.
“The FDA, drug sponsors, contract research organizations, and providers all need to work together to identify where the problems lie and then come up with recommendations for improvement,” he said. “ISMP, along with several pharmacists who oversee investigational drugs in their organizations, have approached the FDA to ask them to look into how investigational drugs are labeled. We are hopeful that all the stakeholders can come together to improve the current system.”
ISMP published a two-part series detailing product-related issues with investigational drugs (Part I, April 19, 2018) and strategies for sponsors, FDA, and clinical sites to prevent product-related errors (Part II, May 3, 2018). This series is available on ISMP’s website.
Propofol
FDA also issued an EUA to Fresenius Kabi in early May to allow the marketing of Propoven 2% (propofol 20 mg/mL) emulsion in 100-mL vials in the United States. This product contains double the propofol concentration of Diprivan 1% (10 mg/mL) emulsion, which clinicians are accustomed to using. ISMP warned that if practitioners are unaware, this may result in overdoses.
“Since the propofol being introduced has twice the concentration (2% vs. 1%) that we are used to in the United States, its use should be reviewed by an interdisciplinary committee including pharmacy, nursing, medicine, anesthesia, critical care, and ambulatory care representatives,” Cohen told Today. “Remember that this product is meant for ICU patients on a ventilator, so it is best to limit distribution to critical care units.”
He noted that smart infusion pump drug libraries should be adjusted so the new concentration is listed; flow rates will be half of what they were with the 1% concentration, and infusions should last longer with each 100-mL bottle.
“Be sure to immediately apply the stickers the company is providing on each bottle once received in the pharmacy. Make sure that staff in any unit where the product will be used is aware of the new concentration. And make sure that the bar code on the product works with your scanning system,” said Cohen.
The wall chart above describing key differences between Fresenius Propoven 2% emulsion for injection or infusion and Diprivan 1% is available on FDA’s website. Clinicians should consider hanging it in the pharmacy and critical care units where the products may be used.
Vincristine
On June 18, ISMP released a statement commending FDA for requesting Pfizer to eliminate syringe administration from vincristine’s prescribing information and product packaging.
The labeling for vincristine will now state “To reduce the potential for fatal medication errors due to incorrect route of administration, vincristine sulfate injection should be diluted in a flexible plastic container and prominently labeled as indicated ‘FOR INTRAVENOUS USE ONLY—FATAL IF GIVEN BY OTHER ROUTES.’ ” Preparation and administration of the drug in a syringe also has been totally removed from the package insert.
“Accidental spinal injection of vincristine is uniformly fatal, yet it keeps happening again and again,” Cohen said. He noted two recent incidents— one in Guyana in 2019 and one that occurred in Europe soon after.
Among the contributing factors is that vincristine is often prepared for I.V. administration via a syringe, and the syringe for I.V. use is sometimes sent to the same clinic room where a spinal drug (methotrexate) is given to the same patient. “If someone accidentally gives both drugs intraspinally or mixes up the two drugs, there is no reversal, and it is a slow and painful death that may take days or weeks until the patient stops breathing,” Cohen said.
ISMP has written about this problem since the 1980s, and there have been over 140 deaths since then. A way to prevent this error is to dilute vincristine in a minibag and never use a syringe for I.V. administration.
“Dilution makes the drug package look different than a syringe, and tubing is needed for infusing the drug unlike just injecting from a syringe. Also, the volume in a minibag is much larger than spinal fluid will accommodate,” said Cohen. This method is backed by the World Health Organization, the Joint Commission, the National Comprehensive Cancer Network, ISMP, the International Medication Safety Network, and many others.
Pharmacists should be aware of the changes to vincristine’s package insert and labeling. “Pharmacists should understand that this horrible error can be avoided, and work to entirely rid their systems of syringe administration, which has been the norm for many years,” said Cohen. “Of the over 140 deaths that have occurred, all have been with syringe administration and none with a minibag.”