Life-threatening Reaction to Iron Dextran: Protocol for Induction of Tolerance.

Adverse reactions to iron dextran are usually delayed and consist of joint pain, vomiting, nausea, headache, and fever. Lifethreatening reactions to iron dextran have been reported [1,2]. We report the case of a 48-year-old woman who experienced a severe reaction to iron dextran and who was able to receive the drug after undergoing a series of tolerance induction protocols. The patient had celiac disease and could not absorb oral iron; therefore, she required parenteral iron. At the time of her first reaction, she had been pretreated with 10 mg of prednisolone and 10 mg of loratadine 1 hour before administration of parenteral iron. After receiving 300 mg of iron dextran she experienced a severe reaction consisting of maculopapular rash and hypotension. Administration was stopped. As part of the allergy workup, we performed a skin prick test and intradermal test with ferrous sulfate, ferrous lactate, and iron sucrose based on a previously reported protocol [3]. The results were negative. Because the patient needed iron and there was no alternative route of administration, she was treated with iron dextran utilizing the protocol of Altman et al [4], with some modifications. The patient received the following drugs and doses: intravenous methylprednisolone 50 mg at 13 hours, 7 hours, and 1 hour before administration of iron dextran; intramuscular diphenhydramine (50 mg) and ephedrine (25 mg) 1 hour before iron dextran; and 20 mL of intravenous dextran (150 mg/mL) immediately before iron dextran. The modification consisted of 180 mg of fexofenadine without ephedrine. The target dose was approximately 2 g in 3 days. At the beginning of the protocol, iron dextran (50 mg in 100 mL of normal saline [NS]) was administered intravenously at 20 mL/h. Subsequent doses were administered at 22 hours (100 mg in 250 mL of NS at 40 mL/h), 28 hours (200 mg in 250 mL of NS at 50 mL/h), 47 hours (400 mg in 250 mL of NS at 60 mL/h), 52 hours (500 mg in 250 mL of NS 60 mL/h), 71 hours (500 mg in 250 mL of NS at 80 mL/h), and 75 hours (250 mg in 250 mL of NS at 80 mL/h). The patient tolerated the first and second day with the increasing doses of iron dextran. On the third day, after the third hour of the infusion (60 mg/h), she experienced a maculopapular vasculitic reaction and edema in her legs. We stopped the protocol and treated the reaction with antihistamines and systemic corticosteroids. The skin lesion had resolved completely 24 hours later (Figure). We then adjusted the protocol several times until we were able to administer iron dextran in NS every 3-4 months without a reaction. Our protocol required 10 doses, administered as follows: first dose, 0.1 mg in 0.5 mL; second dose, 0.2 mg in 1 mL; third dose, 0.5 mg in 2.5 mL; fourth dose, 1 mg in 5 mL; fifth dose, 2 mg in 10 mL; sixth dose, 5 mg in 25 mL; seventh dose, 10 mg in 50 mL; eighth dose, 20 mg in 100 mL; ninth dose, 50 mg in 250 mL; tenth dose, 100 mg in 500 mg. The total dose was 188 mg in 944 mL of NS. The first 7 doses were administered continuously for 15 minutes each. The eighth dose was administered over 30 minutes, the ninth over 60 minutes, and the tenth over 90 minutes (total time 4 hours and 45 minutes). Administration of iron is sometimes necessary, even when the patient experiences severe reactions. Altman et al [4], reported the case of a 26-year-old man with chronic malabsorption and gastrointestinal blood loss resulting in iron deficiency anemia and anaphylaxis to iron dextran. Hickman et al [5] reported the case of a 58-year-old woman who developed irritable bowel syndrome after subtotal gastrectomy and severe iron deficiency anemia because of intolerance to impaired absorption of oral iron. The patient experienced a life-threatening reaction after intravenous infusion of iron. The same protocol was used in both cases, and the patients were able to receive 2 g of iron dextran without experiencing a reaction. In the case we report, serum ferritin levels were 6 ng/mL (15-186 interval range) and hemoglobin 7 mg/dL before the protocol of Altman et al [4] was applied. During administration, the patient received a total dose of 800 mg of iron dextran. After