Cases Of Interest
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THE SAFETY AND EFFICACY OF SODIUM FERRIC GLUCONATE:
History And Physical
An 84-year-old woman who refuses blood transfusions was referred to the ATP center for treatment of anemia prior to colectomy for a cecal mass, presumably cancer. She had been in good health all her life, and rarely saw a doctor. She had a change in bowel habits and was found to have a right lower quadrant mass. She took no medication. She had an advanced directive and had signed the hospital's form declaring her refusal to accept blood transfusions. The review of systems was positive for symptoms of anemia, including exertional shortness of breath and fatigue. Physical examination showed a pale woman, who appeared younger than her stated age. Her blood pressure is 120/78 mm Hg, pulse of 98 and was afebrile. Her lungs are clear. The cardiac examination is normal.
Laboratory tests show the hemoglobin is 8.9 gm/dl. The red cell indices show a MCV of 59 fl, MCHC is 32. The white count and differential are normal. The blood smear shows microcytic, hypochromic red cells. The reticulocyte count is 1.2%. The Ferritin level is <10ng/ml.
Evaluation
Prior to being seen in the ATP Center, a consulting hematologist saw that this woman had iron
deficiency anemia, due to chronic gastrointestinal hemorrhage. The surgeon seeing the patient for
colectomy wished the hemoglobin to be approximately 14 gms/dl prior to surgery. The hematologist
started the patient on ferrous sulphate; 325 mg three times a day and surgery was scheduled. A week
later the patient told her physician that she could not tolerate the iron, despite taking it at
meals. She was experiencing abdominal pains and cramps. She was referred to the ATP Center for
intravenous iron and erythropoietin. Upon being seen in the ATP center, she was started on
intravenous ferrous gluconate. This resulted in no reaction, and she was begun on 8 separate
ferrous gluconate infusions of 125 mg., given over a two-week period of time. She experienced
no symptoms from the drug. At the end of two ferrous gluconate infusions, her reticulocyte count
was noted to be 20%. It was felt that since the patient had findings of brisk erythropoiesis, that
erythropoietin therapy could be discontinued. At the end of the two-week period of time, her
reticulocyte count had increased to 35%. By day 21, her hemoglobin level had increased
to 13.8 gm/dl. It should be noted that after two doses of iron, the patient commented upon her
improved sense of well being and feeling much less tired, even though her hemoglobin had not yet
increased.
Comments
In the United States there has been surge in the prescription of IV iron as nephrologists have become comfortable with its use. Such comfort has demanded a healthy respect for the risk-benefit ratio that has applied to the use of what until recently has been the only form of IV iron available in the United States, iron dextran. Sold under the brand names of INFed (Schein Pharmaceutical, Florham Park, NJ) or DexFerrum (American Regent Laboratory, Shirley, NY), iron dextran causes anaphylactic-type reactions in approximately 0.7% of hemodialysis patients treated. Death has rarely occurred as the result of these reactions. The etiology is not well established.
Most IV iron compounds are similar in their steric design. The functional component, the iron core, is densely packed and is protected and solubilized by a carbohydrate species. Given the suspicion that the risk of anaphylaxis relates to the presence of dextran chains, there has been intense interest in the United States in moving towards the use of IV iron compounds that utilize other carbohydrate moieties to stabilize the iron core. One such drug, sodium ferric gluconate complex in sucrose (brand name Ferrlecit; Schein Pharmaceutical, Florham Park, NJ) was approved by the US Food and Drug Administration in 1999.
Nissenson et al randomized patients to be treatment with IV sodium ferric gluconate at either 62.5 mg or 125 mg per hemodialysis for 8 consecutive doses (total dose, 500 or 1,000 mg). The investigators found that the higher dose level, but not the lower, was consistently associated with a significant increase in hemoglobin concentration. Only the high-dose hemoglobin/hematocrit results were significantly better than that of a historical oral iron control group included in the analysis. No serious adverse events were noted during treatment in this study. In addition, Faich and Strobos reported an epidemiological study in 1999. The safety of iron dextran and sodium ferric gluconate was compared via review of spontaneous adverse reaction reporting. They gathered data from the World Health Organization, pharmaceutical manufacturers, and the German Health Bureau. The number of exposures to sodium ferric gluconate was estimated to be 2.5 million per year from 1976 to 1996. During this time period, not a single death was reported involving treatment with sodium ferric gluconate. From 1992 to 1996, iron dextran usage was approximately 3 million doses per year. In contrast to the excellent safety record of sodium ferric gluconate, 31 deaths were reported with the use of iron dextran Taken together, the studies reported in the previous paragraphs provide a wealth of knowledge relating to the safety and efficacy of sodium ferric gluconate. The drug appears to be considerably more effective than oral iron therapy.
References:
1. Nissenson AR, Lindsay RM, Swan S, Seligman P, Strobos J: Sodium ferric gluconate complex in sucrose is safe and effective in hemodialysis patients: North American Clinical Trial. Am J Kidney Dis 33:471-82, 1999
2. Faich G, Strobos J: Sodium ferric gluconate complex in sucrose: safer intravenous iron therapy than iron dextrans. Am J Kidney Dis 33:464-70, 1999
3. Fishbane S, Wagner J, Sodium ferric gluconate complex in the treatment of iron deficiency for patients on dialysis. Am J Kidney Dis. 37:879-83, 2001
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