18 Clinical
Pharmacy Practice News • May 2021
Nutrition
Affordable Alternatives to Ethanol Lock Therapy E
thanol lock therapy—the use of dehydrated alcohol in central line catheters to prevent catheter-related bloodstream infections (CRBSIs)—has been used widely for pediatric patients on home parenteral nutrition (PN). But with ethanol locks becoming exponentially more expensive, clinicians are employing creative alternatives, a speaker said at the ASPEN 2021 Nutrition Science and Practice Conference. Problems started as a result of the FDA’s Unapproved Drugs Initiative (UDI), implemented in December 2020, through which drugs marketed prior to current safety and efficacy requirements needed to be reviewed again, said Ruba Abdelhadi, MD, CNSC, the director of nutrition support at the University of Missouri-Kansas City School of Medicine. Products such as ethanol locks (dehydrated alcohol), neostigmine methylsulfate, vasopressin and selenium had been grandfathered into use but are no longer approved, Abdelhadi said. Then, through the UDI, Belcher Pharmaceuticals in 2018 received orphan drug designation for an injection of dehydrated alcohol, with exclusivity through 2025. The company has been charging $1,000 per milliliter, according to published data from Vizient,
increasing the wholesale acquisition cost by 668%. (Belcher did not respond to repeated requests for comment.)
‘Disastrous Impact’ “The impact of the ethanol shortage has been disastrous for our patients on home PN,” Abdelhadi said. The UDI “really backfired. It was supposed to be a safety initiative, but now it’s putting our patients in danger of developing CRBSIs.” There are other options that clinicians can consider depending on patient profiles, Abdelhadi said: Using ethanol locks with less frequency. Some studies demonstrated a significant reduction in CRBSIs using ethanol locks three days per week (J Pediatr Surg 2010;45[6]:1287-1293) or once weekly (Nutr Clin Pract 2013; 28[2]:226-231) instead of daily. Using different concentrations. Many centers use 70% ethanol, but in a recent survey by the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) Intestinal Rehab Special Interest Group, two centers reported using either 50% or 20% ethanol.
Using antimicrobial locks. This could be done as a preventive strategy for patients with long-term hemodialysis catheters, limited venous access and a history of recurrent central line–associated bloodstream infections (CLABSIs), or those at increased risk for severe sequelae from a CLABSI. Check with your antimicrobial stewardship program at your institution first, Abdelhadi advised. Using other agents shown to reduce CRBSIs that reduce bacterial burden. These agents include tetrasodium EDTA or taurolidine-citrate solution. Abdelhadi also encouraged clinicians to advocate for their patients by informing legislators about this issue, urging the FDA to regulate pharmaceutical products to avoid shortages, asking the FDA to expedite the approval of competing drugs
Table. UDI-Related Price Spikes for Five Drugs
Drug
Regulatory History
Price Increase
Effect on U.S. Drug Spending (annualized, millions) Before UDI After UDI
Dehydrated Alcohol 98% to Dehydrated Alcohol 99%
• Dehydrated alcohol 98% injection solution was first introduced in 1993 for relief of intractable chronic nerve pain • UDI Status: Received 7-year orphan indication.
• $1,295 ➞ $9,950 • WAC increase of 668% on package of 10
28
215a
Neostigmine Methylsulfate
• Developed in 1931; gained formal FDA approval in 2013 • UDI Status: de facto exclusivity
• $157.90 (prior to UDI) ➞ $987.50 (peak during exclusivity) ➞ $173.40 (current) • WAC increase of 525% on package of 10, then gradually decreased to 9.8% above prior WAC price
60.6
205.8b
Selenium 40 mcg/mL to Selenious Acid 60 mcg/mL
• Parenteral selenium first introduced in the 1980s; received formal FDA approval as injection on April 30, 2019 • UDI Status: five-year NCE exclusivity through April 2024
• $443.25 ➞ $8,575 • WAC increase of 1,190%c on package of 25
8.52
84.9d
Tralement (trace elements injection)
• Parenteral trace elements were introduced in the 1970s; Multitrace-5 was first marketed in 1993. • Tralement received formal FDA approval on July 2, 2020. • UDI Status: five-year NCE exclusivity through April 2024
• $312.50 ➞ $537.50 • WAC increase of 72% on package of 25
34.1
58.7e
Vasopressin to Vasostrict
• Developed in 1928; granted formal FDA approval in 2014 • UDI Status: Patent approved as innovation through 2035
• $283.25 ➞ $4,939 • WAC increase of 1,644% on package of 25
30.8
791c
looking to reenter the market, and asking professional society advocacy groups for support. The NASPGHAN Intestinal Rehab Special Interest Group, for example, partnered with the American Academy of Pediatrics to send a letter to the editor of the Journal of Pediatric Gastroenterology and Nutrition, stating the need to “rapidly regain access” to ethanol or other agents used internationally, Abdelhadi said (J Pediatr Gastroenterol Nutr 2020;70[6]:e140-e141). “There’s not necessarily a shortage of these products, but they’re so expensive that we’re having to pull out our drug shortage management toolkit to try to figure out how to use less,” said Erin R. Fox, PharmD, the senior director of drug information and support services at the University of Utah, in Salt Lake City. “It’s really unfortunate.” Abdelhadi’s suggestions to preserve costs are reasonable, commented Steven Lucio, PharmD, BCPS, the senior principal of pharmacy solutions at Vizient. “These products were pretty narrowly defined in terms of their use,” he said. “You might have some ways to manage it, but by and large you don’t have great ways to completely avoid the increased costs.” Additional product categories also were affected by the UDI, Lucio said. For example, in 2014, Par Pharmaceuticals received FDA approval for its vasopressin injection Vasostrict, with patent protection through 2035; the company raised the price by as much as 1,644% for a 25-count package (Table). In most cases, manufacturers going through the UDI process did not conduct new clinical studies but did test purity of the products and reviewed studies already published in the medical literature, summarizing what the drug has done, Lucio said. This makes the price spikes “appear even more egregious,” he stressed. “The increases, as well as the duration of time that competition is removed, seems disproportionate to the work being done.” Given the potential for regulators to revisit the decision on the UDI, Vizient has shared recommendations to support findings of safety and efficacy for unapproved drugs while avoiding the unintended consequences of this initiative, Lucio said: “We’re very much waiting to see what transpires.” —Karen Blum
a
Estimated annual U.S. health care spend since UDI based on 2020 spend.
e
Estimated 2021 annualized U.S. health care spend since UDI.
b
Average annual health care spend, 2014-2019.
c
Calculated to account for concentration change.
NCE, new chemical entity; UDI, Unapproved Drugs Initiative; WAC, wholesale acquisition cost
d
Estimated 2020 annualized U.S. health care spend since UDI.
Source: Vizient (bit.ly/3cYIx7J)
The sources reported no relevant financial disclosures.
