Parenteral Nutrition Trace Element Product Shortage Considerations

The American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) is a community of professionals representing all disciplines and areas of interest in nutrition support therapy.  A.S.P.E.N. 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 supply information, please see these websites:

American Society of Health-System Pharmacists (ASHP), Drug Shortages Resource Center
US FDA, Drug Shortage Program, Current Drug Shortages  
A.S.P.E.N. Latest News on the homepage or the Product Shortages web page

 

During the Intravenous Trace Element shortage period, consider one or more of the following general measures:

  1. Assess 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 supplement products when oral/enteral intake is initiated (excluding patients with malabsorption syndromes).  Note that all products may not have a full spectrum of trace elements nor contain a daily enteral maintenance dose.  Consult a pharmacist for product information.
  3. Reserve intravenous multi-trace element products for those patients receiving PN 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.
  5. 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.1-3
  6. Purchase only as much trace element injections supply as needed.  In the interest of fair allocation to all patients nationally, please do not stockpile.
  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 must 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 rules and regulations.
  9. During prolonged shortages of intravenous multi-trace element products the FDA may approve the temporary importation of alternative products.  These products may have different   trace element profiles, ratios (doses), packaging and labeling than United States products.  The Dear Healthcare Professional Letter accompanying imported products should be read carefully.
  10. Report severe drug product shortage information to the FDA Drug Shortage Program (DSP)US FDA, Drug Shortage Program   
  11. Report any patient problems related to shortages to ISMP Medication Errors Reporting Program (MERP).  To access that reporting mechanism, click here.

Considerations for a shortage of intravenous ADULT multi-trace element product:

  1. The use of intravenous PEDIATRIC or NEONATAL intravenous (IV) multi-trace element products for adults is not recommended.  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 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 first month of therapy to newly-initiated adolescent and adult PN patients who are NOT critically ill nor have pre-existing deficits.

 

Considerations for a shortage of Intravenous 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 neonatal and pediatric 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 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 trace element entities and their related signs and symptoms of deficiencies:

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. Micronutrient Research Workshop5 and 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, alopecia, anorexia, growth failure, delayed sexual maturation, reduced taste sensitivity, poor night vision, immune compromise and impaired wound healing. 1,2

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. Micronutrient Research Workshop6 and 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 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 elastin formation, CNS dysfunction, and hypotonia.1,2

 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. Micronutrient Research Workshop7 and 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, hemolysis, and impaired cellular immunity.  Keshan disease is an endemic cardiomyopathy associated with selenium deficiency in China.1,2

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. Micronutrient Research Workshop8 and 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, and occasionally nausea and vomiting.  In animals, manganese deficiency has been shown to affect reproductive function, and carbohydrate metabolism.1,2

 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 Workshop9 and 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, hyperlipidemia, peripheral neuropathy, and encephalopathy.1,2

 References/Suggested Readings:

  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.full.pdf+html
  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. Wong T. Parenteral trace elements in children: clinical aspects and dosage recommendations. Curr Opin Clin Nutr Metab Care. 2012;15:649-656. 
  5. Jeejeebhoy K. Zinc: an essential trace element for parenteral nutrition. Gastroenterology. 2009;137:S7-S12.
  6. Shike M. Copper in Parenteral Nutrition. Gastroenterology. 2009; 137:S13-S17.
  7. Shenkin A. Selenium in intravenous nutrition. Gastroenterology. 2009;137:S61-S69.
  8. Hardy G. Manganese in parenteral nutrition: who, when, and why should we supplement? Gastroenterology. 2009;137;S29-S35.
  9. Moukarzel A. Chromium in parenteral nutrition: too little or too much? Gastroenterologyl 2009;137:S18-S28.
  10.  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.
  11.  Clark SF. Vitamins and trace elements. In: The A.S.P.E.N. Adult Nutrition Support Core Curriculum, 2nd Edition. Editor: Mueller CM. American Society for Parenteral and Enteral Nutrition. Silver Spring, MD. 2012.
  12.  Fessler TA. Trace elements in parenteral nutrition: a practical guide for dosage and monitoring for adult patients. Nutr Clin Pract. 2013;28:722-729.

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.

Revised by the A.S.P.E.N. Clinical Practice Committee Shortage Subcommittee: Steve Plogsted, PharmD, BCNSP, CNSC (Chair); Gary Brooks, PharmD, BCPS, BCNSP; John DiBaise, MD; Trisha Fuhrman, MS, RD, LD, FADA; Joseph Ybarra, Pharm D, BCNSP. (2013)

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. (2011)

Questions regarding these recommendations should be directed to Peggi Guenter, PhD, RN, A.S.P.E.N. Director of Clinical Practice, Quality, and Advocacy at: [email protected]