8 Clinical
Pharmacy Practice News • October 2020
Nutrition
Making Off-Label Feeding Safer in Pediatrics A
close look at the off-label use of Smoflipid in neonates and pediatric patients has led one hospital to change its treatment algorithm—most critically, administering the alternative lipid injectable emulsion (ILE) earlier to improve the chances of preventing or resolving cholestasis. “We’re now trying to treat children sooner rather than waiting for cholestasis to develop,” said Charles Vanderpool, MD, CNSC, the medical director of the Nutrition Support and Intestinal Rehabilitation Program at Indiana University School of Medicine, in Indianapolis, and a co-author of a new study detailing their findings (JPEN J Parenter Enteral Nutr 2020 May 26. [Epub ahead of print]. doi: 10.1002/jpen.1929). Resolving cholestasis is critical for optimal outcomes. The condition, in which the flow of bile from the liver stops or slows, can lead to intestinal failure–associated liver disease (IFALD), which occurs in 25% to 50% of neonates receiving prolonged parenteral nutrition (Neoreviews 2020;21[9]:e591-e599). Smoflipid (Fresenius Kabi), a lipid emulsion made up of soy, medium-chain triglycerides, and olive and fish oils, has been suggested as a possible treatment for IFALD. However, lipid therapies also have raised concerns given their lower levels of essential fatty acids (EFAs), which increases the risk for EFA deficiency (EFAD). To identify which patient characteristics might best predict responses, the team conducted a retrospective chart review over two years of all
neonates who received Smoflipid therapy at Riley Hospital for Children, in Indianapolis. Among those started on Smoflipid, 42 (89%) had cholestasis. The team compared these patients based on response to the therapy. Sixteen patients (38%) with cholestasis had resolution during Smoflipid therapy. Older age at treatment appeared to improve the chances of resolving cholestasis (58 vs. 33.5 days; P=0.01). Longer treatment with Smoflipid (85.5 vs. 41 days; P=0.001) and lower direct bilirubin at the start of
the therapy (3.7 vs. 5.2 mg/dL; P=0.035) also increased the chances of resolution. The findings led their center to consider Smoflipid therapy for children at risk for cholestasis or who have shown even a modest increase in direct bilirubin, Dr. Vanderpool explained. His team found that EFAD was present in 54% of patients on Smoflipid. However, none of the patients exhibited clinical symptoms of EFAD, such as a dry scaly rash, hair loss or reduced gr ggrowth owth rate. “II think it is a
‘Given that [Smoflipid] is a relatively new lipid emulsion within the United States pediatric medical community, it is important to monitor patients for appropriate dosing, adverse events and safety concerns when used off-label.’ —Charles Vanderpool, MD, CNSC
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safe lipid, but Smoflipid is currently FDA approved for use in adults only,” Dr. Vanderpool said. “Given that it is a relatively new lipid emulsion within the United States pediatric medical community, it is important to monitor patients for appropriate dosing, adverse events and safety concerns when used off-label.” Gordon S. Sacks, PharmD, BCNSP, the senior director of medical affairs for Fresenius Kabi USA, noted that the Mayo Clinic Laboratory fatty acid profile (T:T ratio) reference range of no more than 0.05, used in the study to diagnose EFAD, is much lower than the more traditional Holman Index of no more than 0.2. No patients met the latter definition, Dr. Sacks noted. “Adequate EFA provision is vital in this population to maintain growth and support brain and retinal development,” he added. “We agree with the study authors that use of new products, such as alternative ILEs, warrant close monitoring by a multidisciplinary team that is knowledgeable about interpreting the fatty acid profile (T:T ratio) to establish a diagnosis of EFAD.” Historically, the only ILEs available in the United States were 100% soybean oil. Although effective in preventing EFAD and providing a balance of nutrient sources, these ILEs also have been associated with liver disease in neonates and patients on long-term nutrition therapy (J Parenter Enteral Nutr 2017;41[1 suppl]:3S13S). Over the last few years, pharmacists and dietitians have welcomed additional options, including Smoflipid and Omegaven, also from Fresenius Kabi, as well as Baxter’s Clinolipid. Although Smoflipid is not yet FDA approved for use in children, it is frequently used off-label. Omegaven, on the other hand, is FDA approved for nutrition-associated cholestasis, “and currently has more data to support its use,” said Joseph Ybarra, PharmD, the director of corporate clinical pharmacy for Christus Health, in Irving, Texas. Although Dr. Vanderpool’s study is limited by being retrospective and lacking a protocol for dosing lipids, it provides useful information, Dr. Ybarra said. “Eventually, these therapies will be FDA approved [for children],” he said. “If not dosed properly, Smoflipid will lead to EFAD. With the old products, we never worried about that. Still, while EFAD should be looked at and monitored, it wouldn’t dissuade me from using this in practice. “As we always say, more studies are needed. And this is no exception.” —Lynne Peeples The sources reported no relevant financial relationships other than their stated employment.
