Parenteral Nutrition Trace Element Product Shortage Considerations

There is a growing and critical shortage of trace element injections needed for parenteral nutrition. We have heard from many consumer groups, healthcare systems, and clinicians regarding their short supplies or inability to obtain these products. For the most up-to-date supply information, please see these websites:

American Society of Health-System Pharmacists (ASHP), Drug Shortages Resource Center: http://www.ashp.org/shortages?WT.ac=hp%5FPopLinks%5FDrug%5FShortages US FDA, Drug Shortage Program, Current Drug Shortages: http://www.fda.gov/Drugs/DrugSafety/DrugShortages/ucm050792.htm A.S.P.E.N. News section (on homepage): http://www.nutritioncare.org/
While there are no replacements for trace element injections, dose conservation or alternate therapy measures can be taken. The American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) has developed conservation recommendations and alternate therapy measures in order to cope with the shortages. If the shortage persists, patients will go untreated, have trace element imbalances, or may be withdrawn from required parenteral nutrition therapy. We consider the lack of trace element injections to be a serious health issue for patients requiring parenteral nutrition in the U.S. The U.S. Food and Drug Administration, Drug Shortage Program is working very hard to try to resolve these issues. During the product shortage period, consider one or more of the following measures: 1. Assess each patient as to the indication for parenteral nutrition (PN). 2. Consider providing nutrition and/or supplements via the oral or enteral route when possible. 3. Purchase only as much trace element injections supply as needed. In the interest of fair allocation to all patients nationally, please do not stockpile. 4. Consider prioritizing patients, saving supply for those vulnerable populations such as neonatal, pediatric or short bowel or malabsorption syndromes PN groups. 5. The use of pediatric / neonatal intravenous (IV) multi-trace element products for adults is not recommended. Using pediatric / neonatal IV multi-trace elements for adults may contribute to a shortage of pediatric products. A shortage of pediatric / neonatal IV trace-elements could create a potential risk of trace element deficiencies in neonate and pediatric patients that may have an even greater need for trace elements. Furthermore, pediatric IV multi-trace elements contain

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trace elements in doses or ratios that may be unsuitable for adults. Use caution and carefully review formulations if using neonatal multi-trace element products in pediatric patients. The use of adult multi-trace element products in neonatal and pediatric patients is not recommended. Eliminate the use of trace element additives in IV fluids. Use oral or enteral multi-vitamin / multi-mineral products as much as possible for replacement therapy. Note that all products may not have a full spectrum of trace elements nor contain a daily enteral maintenance dose. Consult a pharmacist for alternative product information. Review the entire portfolio of parenteral nutrition products available nationally. There may be a shortage in one concentration or salt form but availability in another form. Consider compounding PN in a single, central location (either in a centralized pharmacy or as outsourced preparation) in order to decrease inventory waste. Consider a supply outreach to other facilities in your geographic location. Consider decreasing or eliminating the daily amount of trace elements added to the PN. Observe for an increase in deficiencies with the ongoing shortages. Increase your awareness and assessment for signs and symptoms of trace element deficiencies. Monitor serum trace element concentrations or other appropriate serum biochemical markers to evaluate trace element status. Facilities and practitioners need to continue to observe and be compliant with the product labeling (e.g., package insert), USP General Chapter <797> Pharmaceutical CompoundingSterile Preparations, and state Boards of Pharmacy rules and regulations. Report severe drug product shortage information to the FDA Drug Shortage Program (DSP). See: http://www.fda.gov/Drugs/DrugSafety/DrugShortages/ucm142398.htm Report any patient problems related to shortages to ISMP Medication Errors Reporting Program (MERP). To access that reporting mechanism, click here.

Consider one or more of the following measures for managing each trace element shortage and their related signs and symptoms of deficiencies: IV Multi-Trace Element Shortage: 1. When all options to obtain adequate supplies of IV multi-trace element products have been exhausted, ration IV multi-trace element products in PN by reducing the dose by 50% or administering one dose three times a week. 2. Withhold IV multi-trace element products from patients receiving partial enteral / parenteral nutrition or who can tolerate oral / enteral supplements. Consider withholding multi-trace element products for first month of therapy to newly-initiated adolescent and adult PN patients who are NOT critically ill nor have pre-existing deficits. 3. If IV multi-trace element products are no longer available, administer individual parenteral trace elements. IV Zinc Shortage: 1. Use oral / enteral supplementation if possible. 2. For further information, see the paper on zinc from the 2009 A.S.P.E.N. 1 Micronutrient Research Workshop. 3. Signs and symptoms of zinc deficiency: Dermatitis, alopecia, anorexia, growth failure, delayed sexual maturation, reduced taste sensitivity, poor night vision, 2 immune compromise and impaired wound healing. IV Copper Shortage: 1. Use oral / enteral supplementation if possible. 2. For further information, see the paper on copper from the 2009 A.S.P.E.N. 3 Micronutrient Research Workshop.

3. Signs and symptoms of copper deficiency: Hypochromic, microcytic anemia and neutropenia are common findings. Hypercholesterolemia may be observed. Children may exhibit skeletal demineralization. In premature infants signs may include depigmentation of hair and skin, aortic aneurysm associated with impaired 2 elastin formation, CNS dysfunction, and hypotonia. IV Selenium Shortage: 1. Use oral / enteral supplementation if possible. 2. For further information, see the paper on selenium from the 2009 A.S.P.E.N. 4 Micronutrient Research Workshop. 3. Signs and symptoms of selenium deficiency: Deficiency usually takes years to develop. Symptoms include cardiomyopathy, myalgias, myositis, hemolysis, and impaired cellular immunity. Keshan disease is an endemic cardiomyopathy 2 associated with selenium deficiency in China. IV Manganese Shortage: 1. No need to supplement (during shortage) unless signs and symptoms of clinical deficiency. 2. For further information, see the paper on manganese from the 2009 A.S.P.E.N. 5 Micronutrient Research Workshop. 3. Signs and symptoms of manganese deficiency: Weight loss, transient dermatitis, and occasionally nausea and vomiting. In animals, manganese deficiency has 2 been shown to affect reproductive function, and carbohydrate metabolism. IV Chromium Shortage: 1. No need to supplement (during shortage) unless signs and symptoms of clinical deficiency. 2. For further information, see the paper on chromium from the 2009 A.S.P.E.N. Micronutrient Research Workshop. 3. Signs and symptoms of chromium deficiency: Glucose intolerance, hyperlipidemia, 2 peripheral neuropathy, and encephalopathy. References: 1. Jeejeebhoy K. Zinc: an essential trace element for parenteral nutrition. Gastro 2009;137:S7S12. 2. Jensen GL and Binkley J. Clinical manifestations of nutrient deficiency. JPEN J Parenter Enteral Nutr 2002;26;S29-S33. 3. Shike M. Copper in Parenteral Nutrition. Gastro 2009; 137:S13-S17. 4. Shenkin A. Selenium in intravenous nutrition. Gastro 2009;137:S61-S69. 5. Hardy G. Manganese in parenteral nutrition: who, when, and why should we supplement? Gastro 2009;137;S29-S35. 6. Moukarzel A. Chromium in parenteral nutrition: too little or too much? Gastro 2009;137:S18S28. For the complete 2009 A.S.P.E.N. Research Workshop on Micronutrients in Parenteral Nutrition, see Gastroenterology, Supplements at: http://www.gastrojournal.org/supplements (enter 2009 and November) Important Note: These recommendations do not constitute medical or professional advice, and should not be taken as such. To the extent the information published herein may be used to assist in the care

of patients, this is the result of the sole professional judgment of the attending health professional whose judgment is the primary component of quality medical care. The information presented herein is not a substitute for the exercise of such judgment by the health professional. Developed by the A.S.P.E.N. CPC Shortage Subcommittee: Beverly Holcombe, PharmD, BCNSP, FASHP (Chair); Deborah A Andris MSN, APNP; Gary Brooks PharmD, BCPS, BCNSP; Deborah R Houston , PharmD, BCNSP; and Steven W. Plogsted PharmD, RPh, BCNSP. Approved by the Clinical Practice Committee, and the A.S.P.E.N. Board of Directors. Questions regarding these recommendations should be directed to Peggi Guenter, PhD, RN, CNSN, A.S.P.E.N. Director of Clinical Practice, Advocacy and Research Affairs at: peggig@aspen.nutr.org