2021 Parenteral Nutrition Multivitamin 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. These parenteral multivitamin product shortage considerations were approved by the ASPEN Clinical Practice Committee and the Board of Directors. 

Webinar: "Optimizing Patient Care During a Multivitamin Shortage"—Recorded March 4, 2021
A recording of this free informational webinar on managing current intravenous multivitamin shortages across the age continuum and the safe use of temporarily imported multivitamins is available in the  ASPEN eLearning Center.

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

American Society of Health-System Pharmacists (ASHP)

Drug Shortages U.S. FDA Drug Shortages

ASPEN Product Shortage Latest News

Adult Intravenous Multivitamin Shortage

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

1. The use of pediatric intravenous multivitamins for adults is not recommended. Using pediatric intravenous multivitamins for adults may contribute to a shortage of pediatric products. A shortage of pediatric intravenous multivitamins could create a potential risk of vitamin deficiencies in neonatal and pediatric patients that may have an even greater need for vitamins. Furthermore, pediatric intravenous multivitamins contain vitamins in doses or ratios that may be unsuitable for adults.
2. Assess each patient as to the indication for PN and provide nutrition via the oral or enteral route when possible. Consider switching to oral or enterally administered multivitamins when oral/enteral intake is initiated (excluding patients with malabsorption syndromes). Oral liquid, sublingual, chewable or gummy multivitamin products may not provide a complete vitamin profile. The vitamin profile should be reviewed, and missing components supplemented, if available. Note many oral liquid medications contain sorbitol that may cause diarrhea or gastrointestinal intolerance.
3. Reserve intravenous multivitamins for those patients receiving solely PN or those with a therapeutic medical need for intravenous multivitamins.
4. When all options to obtain intravenous multivitamins have been exhausted, ration intravenous multivitamins in PN, such as reducing the daily dose by 50% or giving one multivitamin infusion dose three times a week.
5. If intravenous multivitamins are not available, administer individual parenteral vitamin entities. Thiamine, ascorbic acid, pyridoxine, and folicacid should be given daily. Thiamine is critical as several deaths have resulted from cardiac failure due to thiamine deficiency when patients on long-term PN did not receive vitamins for three to four weeks. Patients receiving a carbohydrate load are particularly susceptible to thiamine deficiency. It should also be noted that megaloblastic anemia secondary to folate deficiency has been reported in patients receiving PN who did not receive folate for 4-5 weeks. Suggested daily intravenous doses are thiamine 6 mg, folate 0.6 mg, ascorbic acid 200 mg, and pyridoxine 6 mg unless deficiency not suspected or otherwise clinically indicated. Intravenous vitamin K dosing is 0.5-1 mg/day or 5-10 mg per week. Administer cyanocobalamin (B12) 100-1000 mcg intramuscular or deep subcutaneous at least once monthly, 500 mcg intranasal once weekly or 1000 mcg sublingual once daily.
6. Purchase only as much supply as needed. In the interest of patient safety and fair allocation to all patients nationally, please do not stockpile.
7. During prolonged shortages of intravenous multivitamin products, the FDA may approve the temporary importation of alternative products. These products may have different vitamin profiles, ratios (doses), packaging and labeling than United States products. The Dear Healthcare Professional Letter accompanying imported products should be read carefully.
8. 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.
9. 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.
10. Report severe drug product shortage information to the FDA Drug Shortage Program (DSP).
11. Report any patient adverse events or medication hazard related to shortages to ISMP Medication Errors Reporting Program (MERP). 

Pediatric Intravenous Multivitamin Shortage

During the shortage period, consider one or more of the following 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 multivitamins when oral/enteral intake is greater than 50% of needs (excluding patients with malabsorption syndromes). Oral liquid, sublingual, chewable or gummy multivitamins may not provide a complete vitamin profile. The vitamin profile should be reviewed, and missing components supplemented, if available. Note many oral liquid products contain sorbitol that may cause diarrhea or gastrointestinal intolerance.
3. Reserve pediatric intravenous multivitamins for children less than 2.5 kg or less than 36 weeks gestational age.
4. Consider use of adult intravenous multivitamins for children during the shortage; use 5 mL of adult multivitamins in all children weighing greater than or equal to 2.5 kg or gestational age of 36 weeks and older while saving the pediatric product for smaller neonates in order to conserve the supply. Supplement intravenous vitamin K daily (total daily dose = 200 mcg). The vitamin K content of the adult multivitamin product should be noted when supplementing with additional vitamin K. See Table below for ingredients in intravenous multivitamin products.
   
5. If no pediatric intravenous multivitamins are available, infants less than 2.5 kg or less than 36 weeks gestation should receive an adult intravenous multivitamin at a daily dose of 1 mL/kg up to a maximum of 2.5 mL/day. Supplement intravenous vitamin K daily (total daily dose = 200 mcg). The vitamin K content of the adult multivitamin product should be noted when supplementing with additional vitamin K. See Table below for ingredients in intravenous multivitamin products.
6. When using adult intravenous multivitamin products in neonates be aware that these products contain propylene glycol, polysorbate, and aluminum, which may be toxic to neonates. Adult intravenous multivitamins may contain more aluminum than pediatric products. Clinical judgement must prevail by weighing potential vitamin deficiencies against potential propylene glycol, polysorbate and aluminum toxicity.
7. Use the full adult dose (10 mL) of adult intravenous multivitamins for children greater than 11 years of age. (Please refer to the adult multivitamin recommendations in the event of a concurrent shortage.)
8. If neither pediatric nor adult intravenous multivitamins are available, administer individual parenteral vitamin entities in doses that are appropriate for the patient’s age and weight. Thiamine, ascorbic acid, pyridoxine, and folic acid should be given daily. Thiamine is critical as several deaths have resulted from cardiac failure due to thiamine deficiency when patients on long-term PN did not receive vitamins for three to four weeks. Patients receiving a carbohydrate load are particularly susceptible to thiamine deficiency.
9. Purchase only as much supply as needed. In the interest of patient safety and fair allocation, do not stockpile.
10. During prolonged shortages of intravenous multivitamin products, the FDA may approve the temporary importation of alternative products. These products may have different vitamin profiles, ratios (doses), packaging and labeling than United States products. The Dear Healthcare Professional Letter accompanying imported products should be read carefully.
11. 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.
12. 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.
13. Report severe drug product shortage information to the FDA Drug Shortage Program (DSP).
14. Report any patient adverse events or medication hazard related to shortages to ISMP Medication Errors Reporting Program (MERP).

Table 1 U.S. Commercially Available Intravenous Multivitamin Products

* 1 mg Vitamin A = 3,300 USP units
5 mcg Vitamin D = 200 USP units
10 mg Vitamin E = 10 USP units
** 0.7 mg Vitamin A = 2,300 USP units
10 mcg Vitamin D = 400 USP units
7 mg Vitamin E = 7 USP units
*** Maximum, labeled concentration at product expiration date; Pfizer products vary depending if it is unit vial, single-dose or multi-dose packaging.
Consult manufacturer’s product literature for a complete list of inactive ingredients.

Suggested Readings-Adult Patients:

• Ayers P, Adams S, Boullata JI, et al. A.S.P.E.N. Parenteral nutrition safety consensus recommendations. JPEN J Parenter Enteral Nutr. 2014;38;296-333.
• Task Force for the Revision of Safe Practices for Parenteral Nutrition: Mirtallo J, Canada T, Johnson D, Kumpf V, Petersen C, Sacks G, Seres D, Guenter P. Safe practices for parenteral nutrition. JPEN J Parenter Enteral Nutr. 2004;28:S39- S70. Errata: J Parenter Enteral Nutr. 2006;30: 177.
• Boullata JI, Gilbert K, Sacks G, et al. A.S.P.E.N. Clinical guidelines: Parenteral nutrition ordering, order review, compounding, labelling, and dispensing. JPEN J Parenter Enteral Nutr. 2014;38:334-371.
• Centers for Disease Control and Prevention. Deaths associated with thiamine-deficient total parenteral nutrition. MMWR Morb Mortal Wkly Rep. 1989;38:43.
• Centers for Disease Control and Prevention. Lactic acidosis traced to thiamine deficiency related to nationwide shortage of multivitamins for total parenteral nutrition -- United States, 1997. MMWR Morb Mortal Wkly Rep. 1997 Jun 13;46:523-528.
• Romanski SA, McMahon MM. Metabolic acidosis and thiamine deficiency. Mayo Clin Proc. 1999;74:259-263.
• Sriram K, Manzanares W, Joseph K. Thiamine in nutrition therapy. Nutr Clin Pract. 2012;27:41-50.
• Giacalone M, Martinelli R, Abramo A, et al. Rapid reversal of severe lactic acidosis after thiamin administration in critically ill adults: a report of 3 cases. Nutr Clin Pract. 2015; 30:104-110.
• Ferrie S. Case report of acute thiamine deficiency occurring as a complication of vitamin-free parenteral nutrition. Nutr Clin Pract. 2012;27:65-68.
• Alloju M, Ehrinpreis NM. Shortage of intravenous multivitamin solution in the United States. N Engl J Med. 1997;337:54.
• Kudsk KA, Holcombe BJ, Bernstein E. Response to shortage of intravenous multivitamin solution in the United States. N Engl J Med. 1997;337:54.
• Rulewski N. Response to shortage of intravenous multivitamin solution in the United States. N Engl J Med. 1997;337:54.
• Temeck J, Sobel S. Response to shortage of intravenous multivitamin solution in the United States. N Engl J Med. 1997;337:55.
• Francini-Pesenti F, Brocadello F, Famengo S, et al. Wernicke’s encephalopathy during parenteral nutrition. J Parenter Enteral Nutr. 2007;31:69-71.
• Velez RJ, Myers B, Guber MS. Severe acute metabolic acidosis (acute beriberi): an avoidable complication of total parenteral nutrition, JPEN J Parenter Enteral Nutr. 1985:9:216-9.
• Hahn JS, Berquist W, Alcorn DM, Chamberlain L, Bass D. Wernicke encephalopathy and beriberi during total parenteral nutrition attributable to multivitamin infusion shortage. Pediatrics. 1998;10: E1.
• Vortmeyer AO, Hagel C, Laas R. Haemorrhagic thiamine deficient encephalopathy following prolonged parenteral nutrition.  Neurol Neurosurg Psychiatry. 1992;55:826-829.

Suggested Readings-Pediatric and Neonatal Patients:

• Corkins MR, Griggs KC, Groh-Wargo S, Han-Markey TL, Helms RA, Muir LV, Szeszyski EE, Task Force on Standards for Specialized Nutrition Support for Hospitalized Pediatric Patients and the American Society for Parenteral and Enteral Nutrition Board of Directors. Standards for Specialized Nutrition Support: Hospitalized Pediatric Patients. Nutr Clin Pract. 2013;28:263-276.
• Koo W, Christie J, Saba M, Lulic-Botica M, Warren L. Water-soluble essential micronutrients. In: Corkins MR, ed. A.S.P.E.N. Pediatric Nutrition Support Core Curriculum, 2^nded. Silver Spring: A.S.P.E.N., 2015:69-90.
• Koo W, Saba M, Lulic-Botica M, Christie J. Fat-soluble vitamins. In: Corkins MR, ed. A.S.P.E.N. Pediatric Nutrition Support Core Curriculum, 2^nd ed. Silver Spring: A.S.P.E.N., 2015:91-106.
• The American Society for Parenteral and Enteral Nutrition Aluminum Task Force: Pamela J. Charney, MS, RD, LD, CNSD, Chair.   A.S.P.E.N. Statement on Aluminum in Parenteral Nutrition Solutions Nutr Clin Pract, Aug 2004; 19: 416-417.
• Poole RL, Schiff L, Hintz SR., et al. Aluminum Content of Parenteral Nutrition in Neonates: Measured Versus Calculated Levels. J Pediatr Gastroenterol Nutr, 2010: 50(2):208-211.
• American Academy of Pediatrics Committee on Drugs. “Inactive” ingredients in pharmaceutical products: Update (subject review). Pediatrics 1997; 99:268-278.
• Greene HL, Hambidge KM, Schanler R, et al. Guidelines for the use of vitamins, trace elements, calcium, magnesium, and phosphorus in infants and children receiving total parenteral nutrition: Report of the Subcommittee on Pediatric Parenteral Nutrient Requirements from the Committee on Clinical Practice Issues of the American Society for Clinical Nutrition. Am J Clin Nutr 1988;48:1324-1342.
• 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.
• Oriot D, Wood C, Gottesman R, Huault G. Severe lactic acidosis related to acute thiamine deficiency. JPEN J Parenter Enteral Nutr. 1991;15:105-109.
• Klein CJ. Nutrient Requirements for Preterm Infant Formulas. J Nutr 2002; 132:1395S-1577S.

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.

Questions regarding these recommendations should be directed to Allison Blackmer, PharmD, BCPS, BCPPS, FCCP, FASPEN, Director, Clinical Practice, Quality and Advocacy, ASPEN at [email protected].