Finding a safe and effective intravenous iron treatment for restless legs syndrome.

摘要

Until 1989, recommendations for use of parenteral iron have been supported by little more than folklore. In 1954, Baird and Padmore introduced the first high molecular weight (HMW) iron dextran (ID), Imferon (Fisons, Homes Chapel, England), for parental administration to treat iron deficiency [1]. Reports of anaphylaxis, although uncommon, led to recommendations that parenteral iron be given only in extreme clinical situations [2]. The limited use and knowledge about intravenous (IV) iron administration continued until 1987, when Eschbach et al. [3] showed that intravenous (IV) iron markedly improved erythropoietic responses to recombi-nant erythropoietin (EPO) in dialysis patients. Adding IV iron to the anemia treatment paradigm improved by 50% the response of dialysis patients [3,4]. This combination effectively eliminated the need for transfusion to avoid severe anemia in dialysis patients. By 1991, the standard of care for dialysis associated anemia included IV iron supplementation. At the same time LMW ID (INFeD, Schein [now Watson]) was released for clinical use. In 1991, Fisons ceased distribution of the HMW iron dextran, Imferon, and it was permanently removed from the market in 1992 [5]. In 1996 another HMW iron dextran, Dexferrum (American Regent Pharmaceuticals), a product similar to Imferon, and the subject of this editorial, was approved. HMW ID provided a less expensive alternative to LMW ID, which remained the major product used. In 1997, LMW ID became unavailable for a short while necessitating the use of HMW ID in dialysis patients. During this time there was an 11-fold increase in reported SAE's to the FDA [6]. In 1998 an article in the Nursing Journal of the American Nephrology Association recommended that the use of Dexferrum be abandoned [7]. Similar conclusions were reached by Mamula in children with inflammatory bowel disease [8]. At approximately the same time two intravenous iron salts, ferric gluconate (Ferrlecit, Schein [now Watson]) and iron sucrose (Venofer, American Regent), were introduced for use in dialysis associated anemia. Two retrospective studies [9,10] showed that virtually all SAEs with IV iron were due to iron dextran prior to the awareness of the differences in safety between the high and low molecular weight products. Since the salts were almost always well tolerated in iron dextran sensitive patients, ferric gluconate and iron sucrose rapidly replaced iron dextran for treatment of dialysis patients.