David F. Driscoll, PhD

Chronic exposure to aluminum (Al) from injectables can cause significant clinical problems, including neurological, bone, and liver diseases. These adverse effects are most likely to occur in individuals receiving long-term intravenous therapy, such as home total parenteral nutrition (TPN) patients, but can also occur in premature infants and neonates over relatively short-term but continuous periods of exposure. Of the types of intravenous infusions containing substantial amounts of aluminum, parenteral nutrition admixtures are notable sources for this contaminant.

The Food and Drug Administration (FDA) has mandated that all manufacturers of injectables reduce the concentration of Al in their respective large-volume parenteral (LVP) products (ie, >100 mL) to a level that does not exceed 25 µg/L. For small-volume parenterals (SVPs) (ie, £100 mL), the amount of Al must be stated on the containers used in the preparation of TPN admixtures. Hence, with this information, the pharmacist can estimate the total Al exposure for a given TPN admixture. Consequently, the daily human exposure to Al should not exceed 5 µg/kg/d in premature neonates and patients with impaired renal function. Compliance with this mandate was originally scheduled to become effective on January 26, 2001, but has been extended several times, most recently to July 26, 2004.¹

Historically, the major parenteral additives containing aluminum in TPN admixtures include (in decreasing Al concentration): 1) sodium/potassium phosphates injection; 2) calcium gluconate; 3) ascorbic acid; 4) folic acid; 5) phytonadione; 6) multivitamins; 7) albumin; and 8) heparin. Clearly, not all forms (ie, brands) of TPN additives contain the same concentration of aluminum, nor has the concentration been consistent within batches from the same manufacturer. In addition to identifying the Al content of TPN additives, the FDA mandate will also provide for consistency of Al concentration between batches. In a previous Newslines edition, an example of a typical TPN admixture for an adult patient and the subsequent calculations of the resultant cumulative amount of Al from various additives was presented.² However, the Al content data used to make these estimates were derived from a 1986 clinical publication.³ The present report will make the Al content calculations using the most recent information (Tables 1 and 2) provided by a major commercial manufacturer using validated methods of analysis that comply with the new FDA mandate. Finally, a stepwise algorithm is provided in making these calculations (Table 3), but it is recognized that these estimations will likely become a standard output on the TPN label from automated compounding devices.

References:

1. Amendment of Regulations on Aluminum in Large and Small Volume Parenterals Used in Total Parenteral Nutrition; Delay of Effective Date.Federal Register 21CFR Part 201, Vol.68,No.106,June 3,2003.
2. Driscoll DF. Calculating the aluminum load in a typical TPN admixture. Newslines. 2003;9(1).
3. Koo WW, Kaplan LA, Horn J,Tsang RC, Steichen JJ. Aluminum in parenteral nutrition solutions —sources and possible alternatives. JPEN. 1986;10:591-595.