Ferumoxytol is an intravenous iron preparation for treatment of the anemia of chronic kidney disease (CKD). It is a carbohydrate-coated, superparamagnetic iron oxide nanoparticle. Because little free iron is present in the preparation, doses of 510 mg have been administered safely in as little as 17 seconds. Two prospective, randomized studies compared two doses of ferumoxytol 510 mg given in 5 +/- 3 days with 3 weeks of oral iron 200 mg/day (as ferrous fumarate) in anemic patients with CKD. One study enrolled 304 patients with stages 1-5 CKD (predialysis), and the other study enrolled 230 patients with stage 5D CKD (undergoing hemodialysis). In both studies, a greater increase in hemoglobin level from baseline to end of study (day 35) was noted in patients who received ferumoxytol compared with those who received oral iron (mean +/- SD 0.82 +/- 1.24 vs 0.16 +/- 1.02 g/dl in patients with stages 1-5 CKD and 1.02 +/- 1.13 vs 0.46 +/- 1.06 g/dl in patients with stage 5D CKD, p<0.001). A greater proportion of both predialysis and hemodialysis patients who received ferumoxytol had hemoglobin level increases from baseline of 1 g/dl or more compared with those who received oral iron (p<0.001). In a prospective, double-blind, crossover study of more than 700 patients with CKD stages 1-5D that compared the safety of ferumoxytol with normal saline injection, the rates of treatment-related adverse events were 5.2% and 4.5%, respectively. Serious treatment-related adverse events were seen in one patient in each treatment group. The most common adverse events with ferumoxytol occurred at the injection site (bruising, pain, swelling, erythema). Dizziness, nausea, pruritus, headache, and fatigue occurred in less than 2% of patients receiving ferumoxytol, with a similar frequency noted after administration of normal saline. In short-term studies, intravenous ferumoxytol was safely and rapidly administered, and was more effective than oral iron therapy in increasing hemoglobin levels in anemic patients with CKD. Long-term clinical trials with clinical outcomes and studies comparing ferumoxytol with other parenteral iron agents will help define the role of ferumoxytol in treating the anemia of CKD.

Although larger studies are required, this small study demonstrates that ferumoxytol can be safe and effective in increasing iron stores, is associated with an increased hemoglobin response, and is well tolerated at a rapid infusion rate.

Background/Aims: This report summarizes the data gathered in four prospective studies of intravenous iron sucrose therapy administered to iron-deficient hemodialysis patients with a history of intolerance to other parenteral iron preparations. Methods: A total of 130 iron dextran- and/or sodium ferric gluconate-sensitive patients received intravenous iron sucrose therapy to correct iron deficiency, and/or maintain body iron stores. A history of intolerance to iron dextran alone was reported in 109 patients, to ferric sodium gluconate alone in 6 patients, and to both iron dextran and ferric sodium gluconate in 15 patients. Therapy with iron sucrose consisted of 100- or 200-mg doses administered undiluted intravenously over 2–5 min, or diluted in normal saline and infused over 15–30 min. Test doses of iron sucrose were not administered. The median cumulative dose was 1,000 mg, with a range of 100–5,000 mg. Results: There were no serious adverse events related to iron sucrose therapy in the 130 patients intolerant to other iron preparations. There were 14 nonserious drug-related adverse events in 8 patients attributed to iron sucrose, none of which resulted in discontinuation of therapy. These events were classified as either of severe (diarrhea), moderate (hypotension, nausea, vomiting), or mild severity (constipation, dry mouth, skin irritation). Conclusion: Iron sucrose therapy is safe and well tolerated in hemodialysis patients intolerant to iron dextran and/or sodium ferric gluconate.

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Background: Erythropoietin (EPO) therapy is a common and effective treatment for the correction of anemia in patients with end-stage renal disease. Simultaneous treatment with angiotensin-converting enzyme (ACE) inhibitors for the control of hypertension and/or heart failure is often necessary. Recent reports in the literature have raised concern about a potential interaction between these drugs, with a resultant decreased EPO efficacy. Methods: To investigate whether this interaction occurs in chronic dialysis patients, we retrospectively reviewed the records of 175 patients receiving chronic dialysis. All study patients were treated with EPO for at least 3 months, and had normal iron indices. Patients were treated with ACE inhibitors for at least 3 months, at a constant daily dose for at least 1 month (group 1, n = 32), or did not receive ACE inhibitors (group 2, n = 143). Patients with infections or overt iron deficiency were excluded. Total weekly EPO doses and hematocrit (Hct)/hemoglobin (Hgb) values in the two groups were compared. Variables known to affect response to EPO were compared, including ferritin, transferrin saturation, dialysis dose and serum aluminum. Results: Total weekly EPO dose was 17,358 ± 6,871 units in group 1 and 17,612 ± 7,744 units in group 2 (p = 0.854). The achieved Hct was 32.1 ± 4.4% (group 1) and 30.5 ± 4.0% (group 2) (p = 0.079). Similarly, Hgb, ferritin, transferrin saturation, Kt/V, and serum aluminum were not different. The dose or duration of ACE inhibitor therapy did not affect Hgb or Hct. Thus, ACE inhibitor therapy does not appear to affect response to EPO in chronic dialysis patients.

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The two monoamine oxidase (MAO) inhibitors phenelzine and brofaromine given for 2 to 3 weeks were compared in six volunteers. Blood pressure sensitivity to intravenous tyramine increased 2.6-fold during phenelzine (60 mg/day) and 4.8-fold during brofaromine, whereas sensitivity to oral tyramine increased more during phenelzine (15.7-fold vs 8.5-fold). After withdrawal of phenelzine, pressor sensitivity to oral tyramine returned to control values within 2 and for more than 8 weeks. Relative bioavailability of conjugated tyramine was elevated sixfold by brofaromine and 11.6-fold by phenelzine. Urinary elimination of tryptamine increased during phenelzine and brofaromine to 12.7-fold and threefold, respectively. 3-Methoxy-4-hydroxyphenylglycol (MHPG) and 3-methoxy-4-hydroxymandelic acid (VMA) excretion decreased during brofaromine significantly by 72% and 49%, respectively. The nonsignificant decrease of MHPG excretion and the increase of intravenous tyramine pressor sensitivity caused by phenelzine are significantly related. The data suggest that the selective reversible MAO-A inhibitor brofaromine has a larger therapeutic safety than phenelzine.

The safety and efficacy of an accelerated iron sucrose dosing regimen in patients with chronic kidney disease.Background. Provision of adequate iron to support erythropoiesis in patients with chronic kidney disease (CKD) is time consuming and may present adherence problems for patients in the outpatient setting. We studied an accelerated regimen of high-dose intravenous iron sucrose therapy in a cohort of iron-deficient, anemic CKD patients.Methods. Intravenous iron sucrose 500 mg was infused over three hours on two consecutive days in 107 CKD patients (glomerular filtration rate, 32.3 Ϯ 19.6 mL/min/1.73m 2 , baseline hemoglobin 10.2 Ϯ 1.7 g/dL). Iron indices (transferrin saturation, ferritin) were measured at baseline and at two and seven days after completion of the iron regimen. Blood pressures were monitored immediately prior to, and hourly throughout the iron sucrose infusions.Results. Transferrin saturation and serum ferritin increased from 18.5 Ϯ 8.5% and 177 Ϯ 123.8 ng/mL at baseline to 40.2 Ϯ 22.3% and 811 Ϯ 294.1 ng/mL in 102 evaluated patients (P Ͻ 0.015). In 55 patients with additional measurements at 7 days post-dosing, the transferrin saturation and ferritin had fallen to 26.3 Ϯ 10.6% and 691 Ϯ 261.8 ng/mL (P Ͻ 0.015 compared to two days' post-dose). Blood pressure rose slightly, but not significantly, throughout the infusions, and altering the infusion rate was not necessary. Two patients had seven adverse events that were considered related to iron sucrose.Conclusion. An accelerated regimen of high-dose intravenous iron sucrose therapy in CKD patients is safe and effective in restoring iron stores, and may potentially save time and improve patient adherence.The provision of adequate iron to support erythropoiesis in iron-deficient patients with chronic kidney disease is often a time-consuming process that strains the resources of clinicians and challenges patient compliance to the dosing regimen. In the United States iron sucrose is approved for the replenishment of iron stores in patients undergoing hemodialysis and erythropoietic therapy.