Nutrition & Life

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] 

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