Correspondence
Shortage of Intravenous Multivitamin Solution in the United States
N Engl J Med 1997; 337:54-55July 3, 1997
- Article
To the Editor:
Intravenous multivitamin solution has not been manufactured in the United States for some time, and supplies are nearly depleted. Thus, since the end of 1996 this preparation has not been available for many patients requiring parenteral nutrition.
A 41-year-old woman with spindle-cell cancer underwent a massive small-bowel resection in February 1996 that resulted in short-bowel syndrome. She was receiving total parenteral nutrition while being cared for at home. She received her last dose of intravenous multivitamin solution in the total parenteral nutrition in November 1996. In January 1997 she was hospitalized with nausea, vomiting, vertigo, and diplopia. Evaluation revealed tachypnea, bilateral sixth-nerve palsies, horizontal nystagmus, conjugate horizontal-gaze palsy, ataxia, and slow mentation. The serum thiamine level was determined and 100 mg of intravenous thiamine was administered. The sixth-nerve palsies and other eye findings were reversed within hours, and the patient's mental status improved. There was partial improvement of the ataxia. A computed tomographic scan and magnetic resonance image were normal. The thiamine level was reported to be less than 0.1 μg per deciliter (normal range, 0.2 to 2). Four months after discharge, with regular thiamine supplementation, the patient's mental status and cranial-nerve function were normal, but mild residual ataxia persisted. She currently uses a walker.
The daily requirement of thiamine is 1.2 to 1.5 mg, with body stores of approximately 30 mg. Intravenous multivitamin solution contains 3 mg of thiamine in the usual daily total-parenteral-nutrition dose, but excess amounts are not stored in the body. Thus, it is not surprising that symptomatic thiamine deficiency developed in our patient in less than two months.
Physicians and other health care providers treating patients receiving parenteral nutrition at home or patients hospitalized for long periods who require total parenteral nutrition should be aware that intravenous multivitamin solution is not currently available and that other ways of delivering vitamins must be used. Oral supplementation may work for some patients, or intravenous infusions of multiple individual vitamins may be necessary.
Murali Alloju, M.D.
Murray N. Ehrinpreis, M.D.
Wayne State University, Detroit, MI 48201Author/Editor Response
The foregoing letter was referred to Astra USA, the American Society for Parenteral and Enteral Nutrition, and the Food and Drug Administration (FDA), whose spokespersons offer the following replies:
To the Editor: Astra USA understands the importance of MVI-12 [Astra's brand of intravenous multivitamin solution] in patient care and the difficulties arising from the current shortage. We welcome the opportunity to inform the medical community of the events that led to this shortage.
In 1996, Centeon L.L.C., our multivitamin manufacturer, purchased new machinery in order to double its production capacity and ensure a reliable supply of products. We felt that this step was necessary because multivitamin infusion products may be life-sustaining and because, apart from Astra USA, there were only two suppliers in the country. What would otherwise have been a temporary interruption in production was complicated by design and engineering problems involving the new equipment. As a result, our finished-goods inventories, which were increased in anticipation of the installation, were quickly exhausted. Coincidentally, Schein Pharmaceuticals stopped making parenteral multivitamins, which resulted in an additional increase in demand for the inventories of the remaining United States suppliers (Astra USA and Fujisawa USA). When Astra recognized that a market shortage was inevitable, we notified the FDA. Although production of our MVI-12 products has resumed, the demand continues to outstrip the supply. We are working diligently to rebuild our inventory and distribution channels and expect the shortage to be resolved within the next few months.
Since the shortage began, Astra USA had worked closely with the FDA, our vitamin manufacturer, and the American Society for Parenteral and Enteral Nutrition (ASPEN) to keep health care professionals informed about the status of our products. We acknowledge the FDA's cooperation and ASPEN's efforts to provide guidelines on alternatives to multivitamin infusion products and their admonitions that clinicians remain vigilant to clinical signs of vitamin deficiency. Until the shortage is over, clinicians may wish to contact ASPEN for regular updates on the status of all multivitamin solutions.
Nigel J. Rulewski, M.D.
Astra USA, Westborough, MA 01581-4500Author/Editor Response
Information available in December 1996 regarding the current shortage of intravenous multivitamins suggested a short-lived problem. This has not proved to be the case and we are not aware of an adequate explanation for the duration or severity of the shortage. The shortage has now spread to Canada and Australia and to pediatric patients within the United States. We now know of 22 cases of thiamine deficiency in patients receiving long-term total parenteral nutrition. All are similar to the case reported by Alloju and Ehrinpreis. As they point out, thiamine is critical. In 1988, at the time of another shortage of intravenous multivitamins, several deaths resulted from cardiac failure due to thiamine-deficient total parenteral nutrition among patients within a few weeks of not receiving vitamins.1
There is currently only one source of pediatric intravenous multivitamins in the United States (MVI-Pediatric, Astra USA), but production does not meet demand. The use of pediatric intravenous multivitamins in adults is causing harm by preventing this product from reaching neonates, for whom there is no alternative treatment. Products available for adults in the United States, MVI-12 (Astra USA), MVC (Fujisawa USA, Deerfield, Ill.), and Multi-12 (Sabex, Quebec, Canada), each contain preservatives, such as propylene glycol, that could be toxic in infants born at less than 36 weeks' gestation.2,3 In addition, patients receiving home care are at increased risk, and we are concerned that treatment recommendations are not reaching them. We have redoubled our efforts to reach those providing home care and urge increased vigilance in the treatment and monitoring of such patients.
ASPEN, along with the FDA, the Centers for Disease Control and Prevention, and others, has developed treatment recommendations that are available on our Web site (http://www.clinnutr.org) and through our free fax-on-demand service, which is available 24 hours a day (800-905-7781; documents 5010, 5012, 5013, and 5014). These recommendations include reducing the frequency of administering intravenous multivitamins to three times per week, using oral supplements in patients able to absorb at least 50 percent of their nutrients enterally (although compliance problems have been reported), or using individual injectable vitamins. ASPEN is also working with the FDA and other manufacturers that may be able to provide parenteral multivitamins for distribution in the United States.
3 ReferencesKenneth A. Kudsk, M.D.
Beverly J. Holcombe, Pharm.D., B.C.N.S.P.
Edward Bernstein, M.P.H.
American Society for Parenteral and Enteral Nutrition, Silver Spring, MD 20910-38051
Deaths associated with thiamine-deficient total parenteral nutritionMMWR Morb Mortal Wkly Rep 1989;38:43-46
Medline2
Glasgow AM ,Boeckx RL ,Miller MK ,MacDonald MG ,August GP ,Goodman SI . Hyperosmolality in small infants due to propylene glycol. Pediatrics 1983;72:353-355
Web of Science | Medline3
MacDonald MG ,Getson PR ,Glasgow AM ,Miller MK ,Boeckx RL ,Johnson EL . Propylene glycol: increased incidence of seizures in low birth weight infants. Pediatrics 1987;79:622-625
Web of Science | Medline
Author/Editor Response
The FDA is working with Astra USA, the manufacturer of MVI-12, to resolve the shortage as soon as possible. ASPEN is also monitoring the situation closely and has provided guidance to physicians and other health care providers.
Jean Temeck, M.D.
Solomon Sobel, M.D.
Food and Drug Administration, Rockville, MD 20857- Citing Articles (3)
Citing Articles
1
K Robien, M M Schubert, Y Yasui, P Martin, R Storb, J D Potter, C M Ulrich. (2006) Folic acid supplementation during methotrexate immunosuppression is not associated with early toxicity, risk of acute graft-versus-host disease or relapse following hematopoietic transplantation. Bone Marrow Transplantation 37:7, 687-692
CrossRef2
Alan L. Buchman. (2006) Etiology and Initial Management of Short Bowel Syndrome. Gastroenterology 130:2, S5-S15
CrossRef3
C REMOND, L VIARD, O PAUT, P GIRAUD, J CAMBOULIVES. (1999) Acidose lactique sévàre et déficit en thiamine au cours d'une nutrition parentérale chez un enfant. Annales Françaises d’Anesthésie et de Réanimation 18:4, 445-450
CrossRef
