Background: We previously compared the safety profile of three formulations of intravenous iron used during 1998-2000 and found higher rates of adverse drug events (ADEs) associated with the use of higher molecular weight iron dextran and sodium ferric gluconate complex compared with lower molecular weight iron dextran. Since that time, iron sucrose has become widely available and clinicians have gained additional experience with sodium ferric gluconate complex.
Methods: We obtained data from the United States Food and Drug Administration (FDA) on ADEs attributed to the provision of four formulations of intravenous iron during 2001-2003, including higher and lower molecular weight iron dextran, sodium ferric gluconate complex and iron sucrose. We estimated the odds of intravenous iron-related ADEs using 2 x 2 tables and the chi(2) test.
Results: The total number of reported parenteral iron-related ADEs was 1141 among approximately 30,063,800 doses administered, yielding a rate of 3.8 x 10(-5), or roughly 38 per million. Eleven individuals died in association with the ADE. Relative to lower molecular weight iron dextran, total and life-threatening ADEs were significantly more frequent among recipients of higher molecular weight iron dextran and significantly less frequent among recipients of sodium ferric gluconate complex and iron sucrose. The absolute rates of life-threatening ADEs were 0.6, 0.9, 3.3 and 11.3 per million for iron sucrose, sodium ferric gluconate complex, lower molecular weight iron dextran and higher molecular weight iron dextran, respectively. Based on differences in the average wholesale price of iron sucrose and lower molecular weight iron dextran in the US, the cost to prevent one life-threatening ADE related to the use of lower molecular weight iron dextran was estimated to be 5.0-7.8 million dollars. The cost to prevent one lower molecular weight iron dextran-related death was estimated to be 33 million dollars.
Conclusions: The frequency of intravenous iron-related ADEs reported to the FDA has decreased, and overall, the rates are extremely low. This is the fourth report suggesting increased risks associated with the provision of higher molecular weight iron dextran. Life-threatening and other ADEs appear to be lower with the use of non-dextran iron formulations, although the cost per ADE prevented is extremely high.