Parenteral Nutrition Trace Element Product Shortage Considerations

The American Society for Parenteral and Enteral Nutrition (ASPEN) is a professional society of physicians, nurses, dietitians, pharmacists, other allied health professionals, and researchers. ASPEN envisions an environment in which every patient receives safe, efficacious, and high quality patient care. ASPEN’s mission is to improve patient care by advancing the science and practice of clinical nutrition and metabolism. ASPEN has developed parenteral nutrition (PN) shortage considerations in order to assist its members and other clinicians in coping with PN shortages for their patients.

For the most up-to-date product shortage information, see these websites:

American Society of Health-System Pharmacists (ASHP), Drug Shortages Resource Center

U.S. FDA Drug Shortages
ASPEN Product Shortage Latest News

During the shortage period, consider one or more of the following measures:

  1. Assess and routinely reassess each patient as to the indication for PN and provide nutrition via the oral or enteral route when possible.
  2. Consider switching to oral or enterally administered multivitamin/multi-mineral/multi-trace element supplement products when oral/enteral intake is initiated (excluding patients with malabsorption syndromes). Supplements may not have a full spectrum of trace elements nor contain a daily enteral maintenance dose. Oral dietary supplements, including over the counter vitamin and mineral products, are not regulated by the U.S. FDA and therefore are not evaluated for purity, efficacy or safety. The bioavailability of orally administered micronutrients is generally lower than that after intravenous administration. Bioavailability also varies depending on the salt form. Consult a pharmacist for product information and selection.
  3. Reserve intravenous trace elements for those patients receiving solely PN-dependent or those with a therapeutic medical need for intravenous trace elements.
  4. If intravenous multi-trace element products are no longer available, administer individual parenteral trace element entities. Dosing guidelines for individual trace elements can be found in the 2012 A.S.P.E.N. position paper Recommendations for Changes in Commercially Available Parenteral Multivitamin and Multi-Trace Element Products.1
  5. Purchase only as much supply as needed. In the interest of patient safety and fair  allocation to all patients nationally, please do not stockpile.
  6. During prolonged shortages of intravenous trace element products, the FDA may approve  the temporary importation of alternative products. These products may have different trace element entities, ratios (doses), packaging and labeling than United States products. The Dear Healthcare Professional Letter accompanying imported products should be read carefully.
  7. Compound 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.
  8. Facilities and practitioners need to continue to observe and be compliant with the product labeling (e.g., package insert), USP General Chapter <797> Pharmaceutical  Compounding-Sterile Preparations, and state Boards of Pharmacy and federal rules and  regulations.
  9. Include PN component shortages and outages in the health care organization’s strategies and procedures for managing medication shortages and outages.  These procedures should include:
    1. a process to identify and monitor patients who receive no intravenous multi-trace  elements or individual trace element entities,
    2. a process to notify providers when this situation occurs, and
    3.  a process to notify patients receiving long-term (e.g. more than 1 month) PN therapy  when their PN formulation has been adjusted for shortages and outages of PN  components.
     
  10. Observe for deficiencies when your institution is experiencing 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.1-4
  11. Report severe drug product shortage information to the FDA Drug Shortage Program  (DSP).
  12. Report any patient adverse events or medication hazard related to shortages to Institute for Safe Medication Practices (ISMP) Medication Errors Reporting Program (MERP).
Considerations for a shortage of intravenous ADULT multi-trace element products:
  1. The use of intravenous Pediatric and Neonatal intravenous (IV) multi-trace element  products for adults is strongly discouraged. Using pediatric or neonatal IV multi-trace  elements for adults may contribute to a shortage of pediatric and/or neonatal products. A  shortage of pediatric or neonatal IV trace-elements could create a potential risk of trace  element deficiencies in neonatal and pediatric patients who may have an even greater  need for trace elements. Furthermore, pediatric and neonatal IV multi-trace elements  contain trace elements in doses or ratios that may be unsuitable for adults. Use caution  and carefully review formulations if using IV neonatal multi-trace element products in  pediatric patients.
  2. When all options to obtain intravenous Adult multi-trace element products have been  exhausted, ration intravenous Adult multi-trace element products in PN, such as reducing  the daily dose by 50% or giving one multi-trace element product infusion three times a  week.
  3. Withhold intravenous Adult multi-trace element products from adult patients receiving  partial enteral/parenteral nutrition or who can tolerate oral/enteral supplements. Consider  withholding intravenous Adult multi-trace element products for the first month of therapy to  newly-initiated adolescent and adult PN patients who are not critically ill nor have preexisting  deficits.
Considerations for a shortage of PEDIATRIC and/or NEONATAL intravenous multi-trace element products:  
  1. Reserve Neonatal intravenous multi-trace element products for neonatal patients.
  2. Reserve Pediatric intravenous multi-trace element products for pediatric patients.
  3. The routine use of intravenous Adult multi-trace element products in pediatric and neonatal  patients is not recommended.
  4. Use the full dose of intravenous Adult multi-trace element product for children greater than  5 years of age. (Refer to the Adult IV multi-trace element shortage recommendations in  the event of a concurrent shortage.)
Consider one or more of the following measures for managing shortages of INDIVIDUAL intravenous trace element entities and their related signs and symptoms of deficiencies:  

IV Zinc Shortage:

  1. Use oral/enteral supplementation if possible. Oral dietary supplements, including over the  counter products containing trace elements, are not regulated by the U.S. FDA and  therefore are not evaluated for purity, efficacy or safety. The bioavailability of orally  administered micronutrients is generally lower than that after intravenous  administration. Bioavailability also varies depending on the salt form. Consult a pharmacist  for product information and selection. Note that oral/enteral zinc supplementation increases  the expression of metallothionein in the enterocytes which can decrease the oral absorption  of copper and may result in copper deficiency.
  2. For general information on zinc see the 2012 A.S.P.E.N. position paper on  Recommendations for Changes in Commercially Available Parenteral Multivitamins and  Multi-Trace Element Products.1
  3. Signs and symptoms of zinc deficiency: Dermatitis (skin rash of face, groin, buttocks, hands  and feet) alopecia, non-healing ulcers, anorexia, low birth weight, growth failure, delayed  sexual development, diarrhea, reduced taste and smell sensitivity, poor night vision,  impaired cognitive function, recurrent infections, immune compromise, and impaired wound  healing.1,2,4-6
  4. Recent papers on zinc deficiency associated with PN component shortages are listed below:
    • Palm E, Dotson B. Copper and zinc deficiency in a patient receiving long-term  parenteral nutrition during a shortage of parenteral trace element products. JPEN J  Parenter Enteral Nutr. 2015;39:986-989.
    • Centers for Disease Control and Prevention. Notes from the field: zinc deficiency  dermatitis in cholestatic extremely premature infants after a nationwide shortage of  injectable zinc—Washington, DC, December 2012 [published correction appears in  MMWR Morb Mortal Wkly Rep. 2013 Mar; 1562(10):196]. MMWR Morb Mortal Wkly  Rep. 2013 Feb 22;62(7):136-137.
    • Ruktanonchai D, Lowe, M, Norton SA, et al. Zinc deficiency-associated dermatitis in  infants during a nationwide shortage of injectable zinc - Washington, DC, and Houston,  Texas, 2012-2013. [published correction appears in MMWR Morb Mortal Wkly Rep 2014 Jan 31;63(4):82]. MMWR Morb Mortal Wkly Rep. 2014 Jan 17;63(2):35-37.
    • Franck AJ. Zinc deficiency in a parenteral nutrition–dependent patient during a  parenteral trace element product shortage. JPEN J Parenter Enteral Nutr. 2014;  38:637-639.
    • Sant VR, Arnell TD, Seres DS. Zinc deficiency with dermatitis in a parenteral nutrition dependent  patient due to national shortage of trace elements. JPEN J Parenter Enteral Nutr. 2016;40:592-595.
    • Maskarinec SA, Fowler VG. Persistent rash in a patient receiving total parenteral  nutrition. J Amer Med Assoc. 2016;315:2223-2224.
     
IV Copper Shortage:
  1. Use oral/enteral supplementation if possible. Oral dietary supplements, including over  the counter products containing trace elements, are not regulated by the U.S. FDA and  therefore are not evaluated for purity, efficacy or safety. The bioavailability of orally  administered micronutrients is generally lower than that after intravenous  administration. Bioavailability also varies depending on the salt form. Consult a  pharmacist for product information and selection. Note that oral/enteral zinc  supplementation increases the expression of metallothionein in the enterocytes which  can decrease the oral absorption of copper and may result in copper deficiency.
  2. For general information on copper see the 2012 A.S.P.E.N. position paper on  Recommendations for Changes in Commercially Available Parenteral Multivitamins and  Multi-Trace Element Products.1
  3. Signs and symptoms of copper deficiency: Hypochromic, microcytic anemia, leukopenia  and neutropenia are common findings. Hypercholesterolemia may be  observed. Children may exhibit skeletal demineralization (osteopenia). In premature  infants signs may include depigmentation of hair and skin, aortic aneurysm associated  with impaired elastin formation, neurologic dysfunction, and hypotonia.1,2,7 Myopathy,  neuropathy and myeloneuropathy have been reported in copper-deficient adults.
  4. Recent papers on copper deficiency associated with PN component shortages are listed  below:
    • Pramyothin P, Kim DW, Young LS, Wichabnsawakun S, Apovian CM. Anemia and  leukopenia in a long-term parenteral nutrition patient during a shortage of parenteral  trace element products in the united states. JPEN J Parenter Enteral Nutr. 2013;37;  425-429.
    • Palm E, Dotson B. Copper and zinc deficiency in a patient receiving long-term  parenteral nutrition during a shortage of parenteral trace element products. JPEN J  Parenter Enteral Nutr. 2015;39:986-989.  
IV Chromium Shortage:  
  1. No need to supplement (during shortage) unless signs and symptoms of clinical  deficiency. Deficiency is rare. Chromium is present as a contaminant in other PN  components. When a clinical deficiency is identified use oral/enteral supplementation if  possible. Oral dietary supplements, including over the counter products containing trace  elements, are not regulated by the U.S. FDA and therefore are not evaluated for purity,  efficacy or safety. The bioavailability of orally administered micronutrients is generally  lower than that after intravenous administration. Bioavailability also varies depending on  the salt form. Consult a pharmacist for product information and selection.
  2. For general information on chromium see the 2012 A.S.P.E.N. position paper on  Recommendations for Changes in Commercially Available Parenteral Multivitamins and  Multi-Trace Element Products.1
  3. Signs and symptoms of chromium deficiency: Glucose intolerance refractory to insulin,  hyperlipidemia, elevated plasma free fatty acids, weight loss, peripheral neuropathy, and  encephalopathy.1,2,8
IV Manganese Shortage:  
  1. No need to supplement (during shortage) unless signs and symptoms of clinical  deficiency. Deficiency is rare. Manganese is present as a contaminant in other PN  components. When a clinical deficiency is identified use oral/enteral supplementation if  possible. Oral dietary supplements, including over the counter products containing trace  elements, are not regulated by the U.S. FDA and therefore are not evaluated for purity,  bioavailability or safety. The bioavailability of orally administered micronutrients is  generally lower than that after intravenous administration. Bioavailability also varies  depending on the salt form. Consult a pharmacist for product information and selection.
  2. For general information on manganese see the 2012 A.S.P.E.N. position paper on  Recommendations for Changes in Commercially Available Parenteral Multivitamins and  Multi-trace Element Products.1
  3. Signs and symptoms of manganese deficiency: Weight loss, transient dermatitis, ataxia  and occasionally nausea and vomiting. In animals, manganese deficiency has been  shown to affect reproductive function, and carbohydrate metabolism.1,2,9
IV Selenium Shortage:  
  1. Use oral/enteral supplementation if possible. Oral dietary supplements, including over  the counter products containing trace elements, are not regulated by the U.S. FDA and  therefore are not evaluated for purity, eficacy or safety. The bioavailability of orally  administered micronutrients is generally lower than that after intravenous  administration. Bioavailability also varies depending on the salt form. Consult a  pharmacist for product information and selection.
  2. For general information on selenium see the 2012 A.S.P.E.N. position paper on  Recommendations for Changes in Commercially Available Parenteral Multivitamins and  Multi-Trace Element Products.1
  3. Signs and symptoms of selenium deficiency: Deficiency usually takes years to develop.  Symptoms include cardiomyopathy, myalgias, myositis, anemia, hemolysis, and  impaired cellular immunity. Keshan disease is an endemic cardiomyopathy associated  with selenium deficiency in China.1,2,10
  4. Recent papers on selenium deficiency associated with PN component shortages are  listed below:
    • Davis, C, Javid PJ, Horslen S. Selenium deficiency in pediatric patients with intestinal  failure as a consequence of drug shortage. JPEN J Parenter Enteral Nutr. 2014;38:15- 118.
     
References:
  1. Vanek VW, Borum P, Buchman A, et al. A.S.P.E.N. position paper recommendations for  changes in commercially available parenteral multivitamin and multi-trace element products.  Nutr Clin Pract. 2012;27:440-491.  http://ncp.sagepub.com/content/27/4/440.short?rss=1&ssource=mfr
  2. Jensen GL and Binkley J. Clinical manifestations of nutrient deficiency. JPEN J Parenter  Enteral Nutr. 2002;26:S29-S33.
  3. Btaiche IF, Carver PL, Welch KB. Dosing and monitoring of trace elements in long-term  home parenteral nutrition patients. JPEN J Parenter Enteral Nutr. 2011;35:736-747.
  4. Pogatschnik C. Trace element supplementation and monitoring in the adult patient on  parenteral nutrition. Pract Gastoenterol. 2014;38:27-38.
  5. Jeejeebhoy K. Zinc: an essential trace element for parenteral nutrition. Gastroenterology 2009;137:S7-S12.
  6. Livingstone C. Zinc: Physiology, deficiency, and parenteral nutrition. Nutr Clin Pract 2015;30:371-382.
  7. Shike M. Copper in Parenteral Nutrition. Gastroenterology. 2009; 137:S13-S17.
  8. Moukarzel A. Chromium in parenteral nutrition: too little or too much? Gastroenterology 2009;137:S18-S28.
  9. Hardy G. Manganese in parenteral nutrition: who, when, and why should we supplement?  Gastroenterology. 2009;137:S29-S35.
  10. Shenkin A. Selenium in intravenous nutrition. Gastroenterology. 2009;137:S61-S69.
Suggested readings:
  • Baker B, Ali A, Isenring L. Recommendations for manganese supplementation to adult  patients receiving long-term home parenteral nutrition: an analysis of the supporting  evidence. Nutr Clin Pract. 2016; 31:180-185.
  • Buchman AL, Howard LJ, Guenter P, Nishikawa RA, Compher CW, Tappenden KA.  Micronutrients in parenteral nutrition: too little or too much? The past, present, and  recommendations for the future. Gastroenterology. 2009;137:S1-S6.
  • Rech M, To L, Tovbin A, Smoot T, Mlynarek M. Heavy Metal in the Intensive Care Unit: A  Review of Current Literature on Trace Element Supplementation in Critically Ill Patients.  Nutr Clin Pract. 2014;29:78-89.
  • Clark SF. Vitamins and trace elements. In: Mueller CM, ed. The A.S.P.E.N. Adult Nutrition  Support Core Curriculum. 2nd ed. Silver Spring, MD: American Society for Parenteral and  Enteral Nutrition, 2012:121-151.
  • Fessler TA. Trace elements in parenteral nutrition: a practical guide for dosage and  monitoring for adult patients. Nutr Clin Pract. 2013;28:722-729.
  • Esper DH. Utilization of nutrition-focused physical assessment in identifying micronutrient  deficiencies. Nutr Clin Pract. 2015;30:194-202.
  • Wong T. Parenteral trace elements in children: clinical aspects and dosage  recommendations. Curr Opin Clin Nutr Metab Care. 2012;15:649-656.
  • Proceedings from the A.S.P.E.N. 2009 Research Workshop. Micronutrients in parenteral  nutrition: Too little or too much? Gastroenterology. 2009;137:S1-S134.
  • Hassig TB, McKinzie BP, Fortier CR, Taber D. Clinical management strategies and  implications for parenteral nutrition drug shortages in adult patients. Pharmacotherapy 2014;34:72-84.
  • Hanson C, Thoene M, Wagner J, Collier D, Lecci K, Anderson-Berry A. Parenteral nutrition  additive shortages: the short-term, long-term and potential epigenetic implications in  premature and hospitalized infants. Nutrients. 2012;4:1977-1988.
  • Mirtallo JM. The drug shortage crisis. JPEN J Parenter Enteral Nutr. 2011;35:433.
  • Institute for Safe Medication Practices. Survey links PN shortages to adverse patient  outcomes. Medication Safety Alert! 2014;34(2) February 13, 2014.
  • Holcombe B. Parenteral nutrition product shortages: impact on safety. JPEN J Parenter  Enteral Nutr. 2012;36(suppl 2):44S-47S.
  • Chan LN. Iatrogenic malnutrition: a serious public health issue caused by drug shortages.  JPEN J Parenter Enteral Nutr. 2013;37:702-704.
  • Guenter P, Holcombe B, Mirtallo JM, Plogsted SW, DiBaise JK; Clinical Practice and Public  Policy Committees, American Society for Parenteral and Enteral Nutrition. Parenteral  nutrition utilization: response to drug shortages. JPEN J Parenter Enteral Nutr. 2014;38:11- 12.
  • Kaur K, O'Connor AH, Illig SM, Kopcza KB. Drug shortages as an impetus to improve  parenteral nutrition practices. Am J Health Syst Pharm. 2013;70:1533-7. Mirtallo JM,  Holcombe B, Kochevar M, Guenter P. Parenteral nutrition product shortages: the A.S.P.E.N.  strategy. Nutr Clin Pract. 2012;27:385-391.
  • Hanson C, Thoene M, Wagner J, Collier D, Lecci K, Anderson-Berry A. Parenteral nutrition  additive shortages: the short-term, long-term and potential epigenetic implications in  premature and hospitalized infants. Nutrients. 2012;4:1977-1988.
  • Ayers P, Adams S, Boullata J, Gervasio J, Holcombe B, Kraft M, Marshall N, Neal T, Sacks  G, Seres D, Worthington P, Guenter P. A.S.P.E.N. Parenteral nutrition safety consensus  recommendations: translation into practice. Nutr Clin Pract. 2014;29:277-282.
  • Boullata J, Gilbert K, Sacks G, Labossiere RJ, Crill C, Goday P, Kumpf V, Mattox TW,  Plogsted S, Holcombe B, A.S.P.E.N. A.S.P.E.N. Clinical Guidelines: Parenteral Nutrition  Ordering, Order Review, Compounding, Labeling, and Dispensing. JPEN J Parenter Enteral  Nutr. 2014;38:334-377.
  • Ayers P, Adams S, Boullata J, Gervasio J, Holcombe B, Kraft M, Marshall N, Neal T, Sacks  G, Seres D, Worthington P and A.S.P.E.N. Board of Directors A.S.P.E.N. Parenteral nutrition  safety recommendations. JPEN J Parenter Enteral Nutr. 2014;38:296-333.
  • Mirtallo J, Canada T, Johnson D, et al: Task Force for the Revision of Safe Practices for  Parenteral Nutrition. Safe practices for parenteral nutrition (Erratum in: JPEN J Parenter  Enteral Nutr. 2006;30(2):177.). JPEN J Parenter Enteral Nutr. 2004;28(6):S39–S70.


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.

Revised by the ASPEN Clinical Practice Committee’s Nutrition Product Shortage Subcommittee: Steve Plogsted, PharmD, BCNSP, CNSC (Chair); Stephen C. Adams, MS, RPh, BCNSP; Karen Allen, MD; M. Petrea Cober, PharmD, BCNSP, PCPPS; June Greaves, RD, CNSC, CD-N, LD, LDN; Kris M. Mogensen, MS, RD, LDN, CNSC; Amy Ralph, MS, RD, CNSC, CSO, CDN; Daniel
Robinson, MD; Ceressa Ward, PharmD, BCPS, BCNSP, BCCCP; and Joe Ybarra, PharmD, BCNSP.

Approved by the ASPEN Clinical Practice Committee and the Board of Directors on July 20, 2016.

Questions regarding these recommendations should be directed to Beverly Holcombe, PharmD, BCNSP, FASHP, FASPEN, Clinical Practice Specialist, ASPEN at [email protected]