Advances in Trace Element Supplementation for Parenteral Nutrition.

Parenteral nutrition (PN) provides support for patients lacking sufficient intestinal absorption of nutrients. Historically, the need for trace element (TE) supplementation was poorly appreciated, and multi-TE products were not initially subjected to rigorous oversight by the United States Food and Drug Administration (FDA). Subsequently, the American Society for Parenteral and Enteral Nutrition (ASPEN) issued dosage recommendations for PN, which are updated periodically. The FDA has implemented review and approval processes to ensure access to safer and more effective TE products. The development of a multi-TE product meeting ASPEN recommendations and FDA requirements is the result of a partnership between the FDA, industry, and clinicians with expertise in PN. This article examines the rationale for the development of TRALEMENT® (Trace Elements Injection 4*) and the FDA's rigorous requirements leading to its review and approval. This combination product contains copper, manganese, selenium, and zinc and is indicated for use in adults and pediatric patients weighing ≥10 kg. Comprehensive management of PN therapy requires consideration of many factors when prescribing, reviewing, preparing, and administering PN, as well as monitoring the nutritional status of patients receiving PN. Understanding patients' TE requirements and incorporating them into PN is an important part of contemporary PN therapy.

Frequency and Associated Costs of Anaphylaxis- and Hypersensitivity-Related Adverse Events for Intravenous Iron Products in the USA: An Analysis Using the US Food and Drug Administration Adverse Event Reporting System.

INTRODUCTION AND OBJECTIVE: Intravenous iron preparations rapidly correct iron deficiency anemia, with the notable drug class effect of rare, yet potentially life-threatening, administration-related hypersensitivity or anaphylactic reactions. The objective of this comparative study was to assess adverse events associated with four intravenous iron preparations and estimated medical costs, in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS: Cases of hypersensitivity reactions and anaphylaxis/anaphylactic shock associated with iron dextran, iron sucrose, ferumoxytol, and ferric carboxymaltose, spontaneously reported to FAERS (1 January, 2014 to 31 December, 2019), were extracted. The reporting odds ratio lower bound 90% confidence interval (ROR05) > 1 and cases ≥ 5 defined a likely signal for a drug-adverse event association. Adverse event-associated medical costs were estimated using Agency for Healthcare Research and Quality/Healthcare Cost and Utilization Project 2016 data. RESULTS: For hypersensitivity reactions, ferumoxytol and iron dextran had the highest ROR05 values (5.00 and 4.35, respectively) and greatest proportions of associated deaths (7.1% and 5.3%), followed by iron sucrose (ROR05 3.94, deaths 2.4%), and ferric carboxymaltose (ROR05 3.03, deaths 0.2%). For anaphylaxis/anaphylactic shock, ROR05 for cases/deaths were: 39.32/13.4%, ferumoxytol; 37.80/4.5%, iron dextran; 17.60/4.7%, iron sucrose; and 8.77/no deaths, ferric carboxymaltose. Downstream medical costs per adverse event were highest with iron dextran (US$8615) and ferumoxytol (US$8164), followed by iron sucrose (US$4212), and ferric carboxymaltose (US$1832). CONCLUSIONS: Reporting rates of hypersensitivity and anaphylaxis with intravenous iron preparations were highest with ferumoxytol and lowest with ferric carboxymaltose in the US FAERS database. Adverse event-related medical costs were highest for iron dextran and ferumoxytol, and lowest for ferric carboxymaltose.

Systematic review of guidelines for the diagnosis and treatment of iron deficiency anemia using intravenous iron across multiple indications.

OBJECTIVE: To explore current recommendations for intravenous (IV) iron use in clinical guidelines for iron deficiency anemia (IDA) across different therapeutic areas and identify recommendations, if any, for the treatment of IDA. METHODS: A literature search was conducted in Medline, EMBASE, BIOSIS, Cochrane Collaboration, and on websites of relevant professional associations. Searches were limited to English publications. 1292 citations were identified, 219 papers were assessed, and 35 guidelines were identified for inclusion. RESULTS: The guidelines covered a variety of geographies: United States (US; n = 10); Europe (n = 11); "Rest-of-World" (n = 9); and "Other" organizations (n = 5). These covered a variety of specialties. Guidelines defined iron deficiency and IDA generally by serum ferritin and transferrin saturation levels. One-fifth of the reviewed guidelines (7 of 35) included no mention or recommendation regarding parenteral iron's utility in the management of IDA. Fifteen guidelines recommended using parenteral iron in the management of IDA. Fewer US guidelines included recommendations around IV iron than in Europe or the rest of the world. Approximately 60% of the guidelines have not been updated in ≥5 years and consequently do not reflect current evidence on the safety and efficacy of IV iron. CONCLUSIONS: While national and international guidelines for management of IDA exist, many are outdated and do not reflect current evidence including, but not limited to, parenteral iron use. Urgent consideration should be given to updating and clarifying management guidelines for IDA using the latest treatment modalities and options, particularly in the US.