Choice of therapy in a patient with a history of intolerance to peroral and intravenous iron therap

Fråga: Choice of therapy in a patient with a history of intolerance to peroral and intravenous iron therapy? Is there any alternative therapy?

A 29-year-old woman with unexplained iron-deficiency anemia for many years has previously experienced rash and abdominal pain after use of oral ferrous sulfate (Duroferon) and ferroglycine sulfate (Niferex), and also with Blutsaft. Intravenous iron saccharate (Venofer) resulted in exanthema and oedema. The details are however unclear. The patient had a gastrointestinal by-pass in 2005, and is further diagnosed with asthma, fibromyalgia, lactose intolerance and back pain. Current medication includes paroxetine, lansoprazole, budesonide, terbutaline and clozapine.

Sammanfattning: Gastrointestinal side effects of oral iron preparations are dose dependant and generally less common with ferroglycine sulfate than with ferrous fumarate and ferrous sulfate. Therefore a peroral low-dose-regimen with ferroglycine sulfate (Niferex) could be attempted. Intravenous administration of iron saccharate (Venofer) is recommended when peroral therapy is not tolerated. For this patient, who has not tolerated iron saccharate intravenously, intramuscular administration of iron dextran (Cosmofer) under observation could be considered. However, caution is advised as parenteral administration infers an increased risk of anaphylactic reactions compared with oral administration and anaphylactic reactions have mostly been reported for iron dextran.

Svar: Oral iron preparations include ferrous fumarate (Erco-Fer), ferrous sulfate (Duroferon) and ferroglycine sulfate (Niferex). Gastrointestinal side-effects are dose dependant, and seems to be less common with ferroglycine sulfate than with ferrous fumarate and ferrous sulfate (1). However, we found no comparative studies on different peroral preparations concerning gastrointestinal side-effects. There was one crossover study where slightly less gastrointestinal adverse events were reported for ferroglycine sulphate compared with ferrous fumarate (2). Skin reactions (exanthema) have been reported for ferrous sulfate and, to lesser extent, for ferroglycine sulfate, but not for ferrous fumarate (1).

When peroral therapy is not tolerated, parenteral therapy is an option. There are three major types of parenteral preparations; iron dextran, iron sucrose/saccharate and ferric gluconate, which is not available in Sweden. Gastrointestinal side-effects and skin reactions are equally common for iron saccharate and for iron dextran (Cosmofer). Angioedema is noted as a rare adverse effect for iron dextran, and only a few cases with angioedema have been reported for iron saccharate.

In studies designed to compare the efficiency of different iron preparations on blood parameters, statistical analyses have not been performed comparing gastrointestinal side-effects but they have been reported to a larger extent for peroral than intravenous iron preparations (3,4,5).

In many countries, iron dextran has been the most commonly used iron compound for intravenous use (6). Systemic reactions to iron dextran given intramuscularly are less common than those to intravenous iron. In about 1% of cases anaphylactoid reactions occur. Desensitization under an umbrella of glucocorticoids, antihistamines, and epinephrine has been carried out successfully.

In one study, 2 allergic reactions occurred among 143 iron dextran-sensitive patients when they were given ferric gluconate (7). Otherwise, we found no information supporting cross-reactivity between different iron formulations, instead we noted several cases where patients with a previous allergic reaction towards one intravenous formulation (mostly iron dextran) could be given another without occurrence of an allergic reaction (7,8,9,10). However, this does not rule out that cross-reactivity between different iron formulations may occur.

We found no reports concerning interactions between iron and paroxetine, lansoprazole, budesonide, terbutaline or clozapine (11). It cannot be excluded that the gastrointestinal bypass in 2005 could contribute to the anemia (12,13). Fass 2007. (The Swedish catalogue of approved medical products) http://www.fass.se (cited 2007-09-27) Aronstam A, Aston DL. A comparative trial of a controlled-release iron tablet preparation (Ferrocontin Continus) and ferrous fumarate tablets. Pharmatherapeutica 1982;3(4):263-7. van Wyck DB, Roppolo M, Martinez CO, Mazey RM, McMurray S; for the United States Iron Sucrose (Venofer) Clinical Trials Group. A randomized, controlled trial comparing IV iron sucrose to oral iron in anemic patients with nondialysis-dependent CKD. Kidney Int 2005;68:2846-56 Agarwal R, Rizkala AR, Bastani B, Kaskas MO, Leehey DJ, Besarab A. A randomized controlled trial of oral versus intravenous iron in chronic kidney disease. Am J Nephrol 2006;26:445-54 Henry DH, Dahl NV, Auerbach M, Tchekmedyian S, Laufman LR. Intravenous ferric gluconate significantly improves response to epoetin alfa versus oral iron or no iron in anemic patients with cancer receiving chemotherapy. Oncologist 2007;12:231-42. Aronson JK, editor. Meyler´s Side effects of drugs. Volume 3 E-I. 15th ed. Amsterdam; Elsevier: (2006) Coyne DW, Adkinson NF Jr, Nissenson AR, Fishbane S, Agarwal R, Eschbach JW, Michael B, Folkert V, Batlle D, Trout JR, Dahl N, Myirski P, Strobos J, Warnock DG; for the Ferlecit investigators. Sodium ferric gluconate compex in hemodialysis patients. II. Adverse reactions in iron dextra-sensitive and dextran-tolerant patients. Kidney Int 2003;63:217-24. van Wyck DB, Cavallo G, Spinowitz BS, Adhikarla R, Gagnon S, Charytan C, Levin N. Safety and efficacy of iron sucrose in patients sensitive to iron dextran: North Americal Clinical Trial. Am J Kidney Dis 2000;36:88-97 Bastani B, Rahman S, Gellens M. Lack of reaction to ferric gluconate in hemodialysis patients with a history of severe reaction to iron dextran. ASAIO J 2002;48:404-6 Sane R, Baribeault D, Rosenberg CL. Safe administration of iron sucrose in a patient with a previous hypersensitivity reaction to ferric gluconate. Pharmacotherapy 2007;27:613-5. SFINX. (cited 2007-09-24) Alvarez-Leite JI. Nutrient deficiencies secondary to bariatric surgery. Curr Opin Nutr Metab Care 2004;7:569-75 Mizon C, Ruz M, Csendes A, Carrasco F, Rebolledo A, Codoceo J, Inostroza J, Papapietro K, Pizarro F, Olivares M. Persistent anemia after Roux-en-Y gastric bypass. Nutrition 2007;23:277-80