ToxicologyToxicity of PolysaccharideIron Complex Exposures Reported toPoison Control CentersWendy Klein-SchwartzOBJECTIVE : To evaluate the toxicity of polysaccharideiron complex (PIC) exposures reported to poison centers in the US.DESIGN : A retrospective analysis of potentially toxic exposures to PIC without concomitant substances reported to the AmericanAssociation of Poison Control Centers (AAPCC) Toxic Exposure Surveillance System from 1990 to 1998 was performed.RESULTS : Of 810 potentially toxic exposures to PIC, 55.9% occurred in females, 43.8% in males; in 0.3%, gender was unknown. Themajority of exposures (74.4%) involved children under six years of age. The reasons for exposure were: 86.7% unintentional, 11.6%intentional, and 1.6% adverse reaction. The most frequently reported clinical effects attributed to PIC were vomiting (n = 23),diarrhea (10), nausea (11), abdominal pain (10), and lethargy/drowsiness (7). While the majority of exposures were managedoutside a healthcare facility, management site varied depending on age (management in non-healthcare facility in 71.8% ofexposures in children under six years of age vs. 44.9% in adolescents and adults). The majority of outcomes (95.6%) were no effect,minor effect, unrelated effect, not followed since nontoxic, or not followed since only minimal toxicity possible. Of two cases coded asmoderate effect, it could not be determined whether the symptoms were related to PIC in one, and in the second case inspection ofthe poison center record revealed that the actual outcome was minor effect. There were no major effects or deaths.CONCLUSIONS : There were no serious adverse events following PIC exposure reported to the AAPCC. Although more data areneeded, these findings suggest reduced toxicity for PIC relative to other forms of iron.KEY WORDS: polysaccharideiron complex, toxicity, poisoning.Ann Pharmacother 2000;34:165-9.Serious injury and death have been reported followingingestion of products containing iron. Iron is the mostnumber of prescription and nonprescription drug productsincluding Niferex, Nu-Iron, and Hytinic products, whichcontain iron concentrations ranging from 18 to 150 mg pertablet or capsule and 100 mg/5 mL elixirs. The oral lethaldose in 50% of ingestions for PIC in rats is estimated to be35000 mg/kg . There are no published data on the toxicityof PIC in humans following administration of the wrongdose (i.e., therapeutic error) or an overdose.frequent cause of pediatric fatalities resulting from unin-tentional ingestions. In 1998, 3948 potentially toxic expo-1sures to iron products and 25 574 exposures to vitaminswith iron were reported to poison centers in the US; chil-dren under six years of age were involved in 63% and 83%of these exposures, respectively. The Food and Drug Ad-2ministration (FDA) issued regulations requiring label3The purpose of this study was to evaluate the toxicity ofPIC using cases reported to poison centers.warnings and unitdose packaging for solid oral iron-con-taining products with 30 mg of iron per dosage unit. TheFDA temporarily exempted carbonyl iron products fromthe packaging requirements on the basis of preliminary an-imal data suggesting reduced toxicity for carbonyl ironcompared with iron salts, as well as based on poison centerdata from 1989 to 1994 that demonstrated no reports ofmajor effects or death in 2714 carbonyl iron exposures.Another nonionic form of iron, polysaccharideironcomplex (PIC), contains approximately 46% elementalMethodsData on potentially toxic exposures to PIC reported by poison centersthroughout the US to the Toxic Exposure Surveillance System (TESS)of the American Association of Poison Control Centers (AAPCC) wereanalyzed. Potentially toxic exposure is defined as a human exposure to asubstance for which there is potential for toxic clinical effects consider-ing the inherent toxicity and dose of the substance. Data on potentially tox-ic exposures were available on Niferex brand products for 19901998.In addition, data were available on Nu-Iron brand products for 19931994and 19971998, and Hytinic products for 19971998. Data were ana-lyzed for exposures to a PIC product as the sole product (PIC withoutconcomitants other than vitamins and minerals).iron by weight. Synthesized by neutralization of a ferric4chloride carbohydrate solution, it is structurally character-ized as cell-contracted Akaganeite. PIC is available in aChanges were made in the AAPCC TESS database in 1993. There-fore, some of the data elements were only available from 1993 to 1998or were defined differently in the earlier time period. In 19901992, clin-Author information provided at the end of the text.www.theannals.comThe Annals of Pharmacotherapy2000 February, Volume 34165Downloaded from at University of York on September