Hypophosphatemia Associated with Intravenous Iron Therapies for Iron Deficiency Anemia: A Systematic Literature Review.

BACKGROUND: Iron deficiency anemia (IDA) is a prevalent yet underdiagnosed condition with a significant impact on quality of life. Oral iron supplementation is often poorly tolerated or yields inadequate response, requiring the use of intravenous iron (IVI) in some patients. Administration of certain IVI preparations has been associated with decreases in serum phosphate levels and clinically significant hypophosphatemia, which has been reported to lead to adverse events including serious fatigue and osteomalacia. OBJECTIVE: The purpose of this study was to systematically assess the prevalence, clinical consequences, and reporting of treatment-emergent hypophosphatemia within literature investigating IVI therapies marketed in the United States (US). METHODS: A systematic literature review (SLR) was conducted using the PubMed database to identify publications reporting serum phosphate levels or rates of hypophosphatemia within adult IDA patient populations receiving current US-marketed IVIs. RESULTS: The SLR yielded 511 unique publications, with 40 records meeting the final inclusion criteria. Most studies did not report phosphate monitoring methodology or an explicit definition of hypophosphatemia. Hypophosphatemia rates ranged from 0.0% to 92.1% for ferric carboxymaltose (FCM), 0.0% to 40.0% for iron sucrose, 0.4% for ferumoxytol, and 0.0% for low-molecular-weight (LMW) iron dextran. Randomized controlled studies described hypophosphatemia as "asymptomatic" or did not report on other associated sequelae. Eleven case reports detailed treatment-emergent hypophosphatemia in patients treated with FCM. Patients with acute hypophosphatemia primarily developed severe fatigue; those with repeated FCM dosing developed chronic hypophosphatemia associated with osteomalacia and bone deformities. CONCLUSION: Studies analyzed in this SLR reported a range of hypophosphatemia rates, with the highest consistently seen in patients treated with FCM. Across the clinical literature, there appeared to be minimal standardization of phosphate monitoring and definitions of hypophosphatemia. Although multiple cases have documented serious clinical consequences of hypophosphatemia associated with certain IVIs, current trials neither consistently nor adequately assess the frequency and severity of treatment-emergent hypophosphatemia and may underestimate its prevalence.

Ferumoxytol for iron deficiency anemia in patients undergoing hemodialysis. The FACT randomized controlled trial
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BACKGROUND: Patients with chronic kidney disease (CKD) undergoing dialysis often require intravenous iron for iron deficiency anemia (IDA). MATERIALS AND METHODS: The Ferumoxytol for Anemia of CKD Trial (FACT), a randomized, multicenter, open-label, phase 4 study, compared the long-term safety and efficacy of ferumoxytol with iron sucrose for the treatment of IDA in patients with CKD undergoing hemodialysis. Patients with IDA and CKD undergoing hemodialysis were randomized 2:1 to ferumoxytol 1.02 g (2 × 510 mg) or iron sucrose 1.0 g (10 × 100 mg) for a 5-week treatment period (TP). Over 11 months, patients underwent additional 5-week TPs whenever IDA (hemoglobin < 11.5 g/dL and transferrin saturation < 30%) was detected. The primary efficacy endpoint was mean change in hemoglobin from baseline to week 5 for each TP. Adverse events were recorded during the study. RESULTS: Overall, 293 patients received ferumoxytol (n = 196) or iron sucrose (n = 97). Ferumoxytol was noninferior to iron sucrose regarding hemoglobin change from baseline to week 5. The mean change in hemoglobin in the ferumoxytol and iron sucrose groups was 0.5 and 0.4 g/dL, respectively, in TP 1 (least-squares mean difference, 0.13; 95% confidence interval, -0.11 to 0.36) and 0.6 and 0.3 g/dL, respectively, in TP 2 (0.30; 0.06 - 0.55). Treatment-related and serious adverse events were similar in both groups; no new safety signals emerged. CONCLUSION: Long-term administration of ferumoxytol has noninferior efficacy and a similar safety profile to iron sucrose when used to treat IDA in patients with CKD undergoing hemodialysis.
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Correction to: The Ferumoxytol for Anemia of CKD Trial (FACT)-a randomized controlled trial of repeated doses of ferumoxytol or iron sucrose in patients on hemodialysis: background and rationale.

Following publication of the original article [1], the authors reported that one of the authors' name is spelled incorrectly. In this Erratum the incorrect and correct author name are shown. The original publication of this article has been corrected.

Efficacy and safety of IV ferumoxytol for iron deficiency anemia in patients with cancer.

PURPOSE: Iron deficiency anemia (IDA) is common in cancer patients due to blood loss and inflammation. Many do not tolerate oral iron or adequately respond. Intravenous (IV) iron is commonly used as an adjunct to erythropoiesis-stimulating agents; data on the use of IV iron monotherapy in these patients are limited. This study aimed to evaluate IV ferumoxytol for the treatment of cancer patients with IDA with a history of unsatisfactory oral iron therapy or in whom oral iron could not be used. PATIENTS AND METHODS: This post hoc analysis of pooled data from two multicenter, randomized, controlled, Phase III trials evaluating IV ferumoxytol (510 mg ×2) vs placebo or iron sucrose (200 mg ×5) included a subgroup of 98 patients with cancer that the investigator identified as the primary cause of their IDA, or with cancer whose IDA was attributed to another comorbid condition (ferumoxytol, n=75; iron sucrose, n=13; placebo, n=10). Gastrointestinal cancers were most common (42), followed by breast (14), cervix (ten), and lung (nine). The primary endpoint was the mean change in hemoglobin (Hgb) from baseline to week 5. RESULTS: At week 5, both ferumoxytol and iron sucrose produced significant increases in Hgb from baseline (1.8 g/dL [P<0.0001] and 1.9 g/dL [P=0.002], respectively). During the studies, 45 patients received chemotherapy, 19 with platinum-based regimens. Erythropoiesis-stimulating agent doses were neither increased >20% nor initiated in any treatment group. Overall rates of adverse events and serious adverse events in the cancer subgroup mirrored those in the overall study population. CONCLUSION: Monotherapy with IV iron appears to be an effective option for cancer patients with IDA who do not respond to or cannot tolerate oral iron therapy.

Cost-effectiveness analysis of intravenous ferumoxytol for the treatment of iron deficiency anemia in adult patients with non-dialysis-dependent chronic kidney disease in the USA.

OBJECTIVE: Ferumoxytol has demonstrated superior efficacy compared with oral iron in treating iron deficiency anemia in chronic kidney disease (CKD) patients. However, an economic evaluation of ferumoxytol has not been conducted. The aim of this study was to analyze the cost-effectiveness of treating iron deficiency anemia in adult non-dialysis-dependent CKD patients with ferumoxytol as compared with oral iron, alone or in combination with erythropoietin-stimulating agents (ESAs). METHODS: A decision analytic model compared health outcomes and costs associated with 5-week outpatient treatment of adult non-dialysis-dependent CKD patients with ferumoxytol or oral iron, each as monotherapy or in combination with ESAs in the USA. Direct costs include the following: drug acquisition and administration, adverse events, and medical management. Efficacy was determined as mean increase in hemoglobin (g/dL) from baseline over the 5-week period. Clinical inputs were derived from patient-level data from two Phase III randomized controlled trials of ferumoxytol vs. oral iron in non-dialysis-dependent CKD patients, and cost inputs from RED BOOK™ and Centers for Medicare and Medicaid Services data. Sensitivity analyses were performed to identify cost drivers and assess the stability of results. RESULTS: The 5-week treatment cost was $2,489, $5,216, $1,298, and $4,263 per patient for ferumoxytol, ferumoxytol with ESAs, oral iron, and oral iron with ESAs, respectively. The corresponding incremental costs per g/dL increase in hemoglobin, relative to ferumoxytol alone, were $398, $3,558, and $4,768 per patient. Efficacy was the main driver of cost-effectiveness for all treatments. Adverse event and medical management costs were the principal drivers of oral iron monotherapy costs, while drug acquisition substantially contributed to the overall cost for the remaining treatments. CONCLUSION: These results suggest that ferumoxytol is a cost-effective treatment for iron deficiency anemia in non-dialysis-dependent CKD patients over a 5-week period compared with oral iron with or without ESAs. Ferumoxytol is more cost-effective as monotherapy.

The Ferumoxytol for Anemia of CKD Trial (FACT)-a randomized controlled trial of repeated doses of ferumoxytol or iron sucrose in patients on hemodialysis: background and rationale.

BACKGROUND: Iron deficiency anemia (IDA) is a common manifestation of chronic kidney disease (CKD), affecting most patients on hemodialysis and imposing a substantial clinical burden. Treatment with iron supplementation increases hemoglobin levels and can reduce the severity of anemia in patients with CKD. While correcting anemia in these patients is an important therapeutic goal, there is a lack of long-term trials directly comparing intravenous iron therapies in patients with CKD receiving hemodialysis. METHODS/DESIGN: The Ferumoxytol for Anemia of CKD Trial (FACT) is a 13-month, open-label, randomized, multicenter, international, prospective study with 2 substudies. Entry criteria for the main study include adults with IDA (defined as hemoglobin <11.5 g/dL [<115.0 g/L] and a transferrin saturation <30%), serum ferritin <800 ng/mL (<1798 pmol/L), and receiving hemodialysis for ≥3 months. Patients are randomized to receive ferumoxytol (1.02 g over 2 doses) or iron sucrose (1.0 g over 10 doses) during the initial 5-week treatment period. Those with persistent/recurrent IDA over the 11-month observation period will receive additional 5-week treatment periods, as appropriate. The primary efficacy endpoint of the main study is the mean change in hemoglobin from Baseline to Week 5 for each treatment period. The secondary efficacy endpoints include the mean change in transferrin saturation from Baseline to Week 5 and the proportion of patients with a hemoglobin increase of ≥1.0 g/dL at any time from Baseline to Week 5. Safety will be assessed through an examination of the adverse event profile over the course of the study. An "oxidative stress" substudy in approximately 100 patients will assess the effects of treatment on biomarkers of oxidative stress/inflammation during the initial 5-week treatment period, and a magnetic resonance imaging substudy in approximately 70 patients will assess the potential for iron deposition in target tissues over 24 months. DISCUSSION: FACT fulfills the need for a long-term comparative trial in patients with IDA and CKD receiving hemodialysis. The efficacy and safety results will provide useful information for guiding therapy in this population. Two hundred ninety-six patients have been enrolled, and completion of the main study is expected soon. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01227616 (registered October 22, 2010); EudraCT number: 2010-022133-28.

Ferumoxytol versus iron sucrose treatment: a post-hoc analysis of randomized controlled trials in patients with varying renal function and iron deficiency anemia.

BACKGROUND: Iron deficiency anemia is highly prevalent in patients with chronic kidney disease and is often treated with intravenous iron. There are few trials directly comparing the safety and efficacy of different intravenous iron products. METHODS: This post-hoc analysis pooled data from 767 patients enrolled in two randomized, controlled, open-label trials of similar design comparing the treatment of iron deficiency anemia with ferumoxytol and iron sucrose across patients with all stages of renal function. One trial was conducted in adults with CKD either on or not on dialysis and the second in adults with IDA of any underlying cause and a history of unsatisfactory oral iron therapy or in whom oral iron could not be used who had normal to no worse than moderately impaired renal function. Patients were categorized by chronic kidney disease stage (i.e., estimated glomerular filtration rate), and the primary efficacy endpoint was the mean change in hemoglobin from Baseline to Week 5. RESULTS: The overall incidence of adverse events was numerically lower in ferumoxytol-treated patients compared to those treated with iron sucrose (42.4 vs. 50.2 %, respectively); the incidence of treatment-related adverse events was generally similar between the two treatment groups (13.6 vs. 16.0 %, respectively). Adverse events of Special Interest (i.e., hypotension, hypersensitivity) occurred at lower rates in those treated with ferumoxytol compared to those treated with iron sucrose (2.5 vs. 5.3 %, respectively). Overall, mean hemoglobin increased in both treatment groups, regardless of degree of renal insufficiency, although greater increases were seen among those with less severe kidney damage. Mean increases in hemoglobin from Baseline to Week 5 were significantly greater with ferumoxytol than with iron sucrose treatment in the subgroup with an estimated glomerular filtration rate ≥90 mL/min (Least Squares mean difference = 0.53 g/dL; p < 0.001). There were no other consistent, significant differences in hemoglobin levels between treatment groups for the other chronic kidney disease categories except for isolated instances favoring ferumoxytol. CONCLUSIONS: The efficacy and safety of ferumoxytol is at least comparable to iron sucrose in patients with varying degrees of renal function. TRIAL REGISTRATION: (CKD-201; ClinicalTrials.gov identifier: NCT01052779; registered 15 January, 2010), (IDA-302; ClinicalTrials.gov identifier: NCT01114204; registered 29 April, 2010).

Ferumoxytol versus placebo in iron deficiency anemia: efficacy, safety, and quality of life in patients with gastrointestinal disorders.

INTRODUCTION: Iron deficiency anemia (IDA) is common in patients with gastrointestinal (GI) disorders and can adversely affect quality of life. Oral iron is poorly tolerated in many patients with GI disorders. Ferumoxytol is approved for the intravenous treatment of IDA in patients with chronic kidney disease. This study aimed to evaluate the efficacy and safety of ferumoxytol in patients with IDA and concomitant GI disorders. PATIENTS AND METHODS: This analysis included 231 patients with IDA and GI disorders from a Phase III, randomized, double-blind, placebo-controlled trial evaluating ferumoxytol (510 mg ×2) versus placebo in patients who had failed or were intolerant of oral iron therapy. The primary study end point was the proportion of patients achieving a ≥20 g/L increase in hemoglobin (Hgb) from baseline to Week 5. Other end points included mean change in Hgb, proportion of patients achieving Hgb ≥120 g/L, mean change in transferrin saturation, and patient-reported outcomes (PROs). RESULTS: Significantly more patients with IDA receiving ferumoxytol achieved a ≥20 g/L increase in Hgb versus placebo (82.1% vs 1.7%, respectively; P<0.001). Mean increase in Hgb (28.0 g/L vs -1.0 g/L, respectively; P<0.001) significantly favored ferumoxytol treatment. Ferumoxytol-treated patients demonstrated significantly greater improvements than placebo-treated patients relative to their very poor baseline PRO scores posttreatment, including improvements in the Functional Assessment of Chronic Illness Therapy-Fatigue questionnaire and various domains of the 36-Item Short-Form Health Survey. Ferumoxytol-treated patients had a low rate of adverse events. CONCLUSION: In this study, ferumoxytol was shown to be an efficacious and generally well-tolerated treatment option for patients with IDA and underlying GI disorders who were unable to use or had a history of unsatisfactory oral iron therapy.

Cognitive effects of oxybutynin chloride topical gel in older healthy subjects: a 1-week, randomized, double-blind, placebo- and active-controlled study.

BACKGROUND AND OBJECTIVE: Oxybutynin is a common antimuscarinic therapy for overactive bladder. Transdermally administered oxybutynin chloride topical gel 10% (OTG) has a low propensity for anticholinergic adverse effects and possibly also a low risk of cognitive impairment. A randomized, double-blind, placebo- and active-controlled study evaluated the effects of OTG on cognitive and psychomotor functions in older healthy adults. METHODS: Healthy adults aged 60-79 years were assigned randomly (1:1:1) to 1-week's treatment with OTG (1 g [100 mg oxybutynin] applied once daily on rotating sites of upper arms/shoulders, abdomen or thighs) plus oral placebo, immediate-release oxybutynin (OXB-IR; 5 mg capsule three times/day) plus placebo gel, or double placebo. Delayed recall Name-Face Association Test (NFAT) score was the primary end point. Treatments were compared by analysis of covariance. RESULTS: Of 152 participants (mean age, 68 years), 49 received OTG, 52 OXB-IR and 51 placebo. NFAT Delayed Recall tests revealed no significant treatment differences (overall, p = 0.2733; OTG vs placebo, p = 0.1551; OXB-IR vs placebo, p = 0.1767). However, a significant effect (p = 0.0294) was noted for the Misplaced Objects Test, with scores declining only for OXB-IR. Approximately twice as many participants receiving OXB-IR (n = 10) as those receiving OTG (n = 5) or placebo (n = 6) showed a significant decline (≥6 points) in Total Recall score for the Hopkins Verbal Learning Test-Revised. No significant effects on psychomotor reaction time were observed. The most common adverse event, dry mouth, occurred in 6.1%, 73.1% and 7.8% of participants receiving OTG, OXB-IR and placebo, respectively. CONCLUSIONS: OTG applied for 1 week had no clinically meaningful effect on recent memory or other cognitive functions in healthy, older adults. CLINICAL TRIAL REGISTRATION: Registered as NCT00752141 at www.clinicaltrials.gov.

Thrombocytosis and venous thromboembolism in cancer patients with chemotherapy induced anemia may be related to ESA induced iron restricted erythropoiesis and reversed by administration of IV iron.

ESA therapy can increase hemoglobin, decrease blood transfusions, and improve quality of life in patients with chemotherapy induced anemia (CIA). Despite its benefits, ESA therapy increases the risk of venous thromboembolism (VTE) in cancer patients by 50% and can also cause iron restricted erythropoiesis in CIA patients, which may augment the tendency to develop VTE. We postulated that thrombocytosis, a risk factor for VTE in cancer patients, in CIA patients on ESA therapy might be a result of ESA induced iron restricted erythropoiesis. We performed a retrospective analysis of 187 CIA patients who were randomized to receive weekly Epoetin and IV ferric gluconate, oral ferrous sulfate, or no iron for 8 weeks. Nineteen patients experienced 29 VTEs, and patients, whose platelets increased to ≥350,000 cells/uL were three times more likely to experience a VTE (OR 2.9, P = 0.036, logistic regression) with a four times greater incidence of VTE (IRR 4.4, P = 0.001, Poisson regression). Patients treated with IV iron were significantly less likely to develop platelets of ≥350,000 cells/uL (IRR 0.7, P = 0.013, Poisson regression) and had a decreased incidence of VTE. Our study suggests that ESA associated VTE in CIA patients may be, in part, related to the thrombocytosis of ESA induced iron restricted erythropoiesis and may be countered by IV iron.

Application drying time for oxybutynin chloride topical gel.

This study determined the median drying time for oxybutynin chloride topical gel (OTG) approved for treatment of overactive bladder was 3.1 minutes, Most participants reported positive perceptions of OTG attributes.

Proteinuria induced by parenteral iron in chronic kidney disease--a comparative randomized controlled trial.

BACKGROUND AND OBJECTIVES: Among patients with chronic kidney disease (CKD), differences in proteinuria are seen between intravenous iron preparations after a single dose exposure. This study examined differences in proteinuria between two intravenous iron preparations after multiple doses. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients with iron-deficiency anemia and CKD, stratified by angiotensin converting enzyme inhibitor (ACEI)/angiotensin receptor-blocker (ARB) use, were randomized to iron sucrose or ferric gluconate. Each patient at 12 centers received 100 mg of study drug weekly for 5 weeks. Urine protein/urine creatinine ratio was measured before each dose and frequently thereafter for 3 hours. RESULTS: Postbaseline data were available from 33 patients receiving iron sucrose and 29 patients receiving ferric gluconate. Although neither preparation of intravenous iron increased the predose level of proteinuria, the proteinuric response to intravenous iron was dependent on the type of iron and ACEI/ARB use. Without ACEIs/ARBs, ferric gluconate tended to cause less proteinuria with repeated iron administration; iron sucrose did not mitigate or aggravate proteinuria. Among patients receiving ACEIs/ARBs, in contrast to ferric gluconate, which produced only mild transient proteinuria, iron sucrose produced a consistent and persistent proteinuric response that was on average 78% greater. CONCLUSIONS: Although multiple doses of either intravenous iron did not increase basal levels of proteinuria, postdose proteinuria was greater with iron sucrose than with ferric gluconate. These data suggest that nephrotoxicity of iron may depend on type of intravenous iron and on ACEI/ARB use. The long-term effects on kidney function need to be further evaluated.

Impact of transdermal oxybutynin on work productivity in patients with overactive bladder: results from the MATRIX study.

BACKGROUND: Overactive bladder syndrome (OAB) is a common condition affecting a significant number of working adults, resulting in increased healthcare utilization, reduced quality of life and decreased work productivity. The MATRIX study was a large, prospective, community-based, observational US study aimed at evaluating the impact of oxybutynin transdermal system (OXY-TDS). In this paper, we report on productivity findings among working adults in MATRIX. METHODS: This study enrolled 2878 adults (aged > or =18 years) with symptoms of OAB from 327 practice sites throughout the US. All subjects received OXY-TDS (3.9 mg/day up to 6 months). Baseline versus end-of-study productivity was measured using the Work Productivity Questionnaire (WPQ). The WPQ includes a subset of questions from the Work Limitations Questionnaire (WLQ) and consists of four scales: (i) physical; (ii) time management; (iii) mental; and (iv) output demands. Overall productivity was measured by the work productivity index score (WPQ Index; a summary score based on scales) and work productivity loss score (WPLS; a measure of reduced output compared with healthy workers). Psychometric performance of the WPQ instrument is also reported, since this study represents the first use of the tool. RESULTS: Of the participants, 52% were of working age (18-65 years) and 38.6% were employed. A total of 1112 working adults participated in MATRIX and were included in this analysis. They had a mean age of 52.4 years; 92.2% were female and 80.9% were Caucasian. Subjects who reported that they were most affected by OAB were also most impaired at work. After OXY-TDS treatment, participants experienced significant improvements in mean scores for all four WPQ scales (p < or = 0.0002) and the mean WPQ Index decreased from 8.2 to 5.5 (p < 0.0001). In addition, the WPLS decreased from 7.7% to 5.2% (p < 0.0001), indicating improvement in work function with OXY-TDS treatment. CONCLUSION: OAB contributes to decreased work productivity due to job interruptions as well as fatigue. OXY-TDS may result in productivity improvement when patients receive 3.9 mg/day via twice weekly patch application for up to 6 months.

Thrombosis with erythropoietic stimulating agents-does iron-deficient erythropoiesis play a role?

Thrombocytosis is common in iron deficiency and resolves following iron repletion. Increased platelet number, whether from iron deficiency or from other causes, may increase the risk of thrombovascular events. One mechanism thought to mediate iron deficiency-induced thrombocytosis is increased erythropoietin production. Similarly, erythropoietic stimulating agents (ESA) have long been known to increase platelet number and frequently lead to functional or absolute iron deficiency. This state of relative or absolute iron deficiency may be the mechanism whereby ESA increase the platelet count. If correct, co-administration of iron should prevent or diminish ESA-driven thrombocytosis. Data from the DRIVE trial in hemodialysis patients do, in fact, suggest that this is the case. Platelet counts in patients receiving IV iron decreased, while they remained unchanged in patients not given iron (mean change -29,000/microl vs. -0/microl; p = 0.017). Other supporting data have been observed in IV iron trials in oncology patients. The harm from higher hemoglobin targets and higher ESA doses may be mediated in part through induction of iron deficiency and thrombocytosis. The major anemia trials of ESAs have not reported platelet data, but should examine the relationship of platelet count, iron deficiency, IV iron administration, and cardiovascular events in greater detail.

Ferric gluconate reduces epoetin requirements in hemodialysis patients with elevated ferritin.

The Dialysis Patients Response to IV Iron with Elevated Ferritin (DRIVE) study demonstrated the efficacy of intravenous ferric gluconate to improve hemoglobin levels in anemic hemodialysis patients who were receiving adequate epoetin doses and who had ferritin levels between 500 and 1200 ng/ml and transferrin saturation (TSAT) < or = 25%. The DRIVE-II study reported here was a 6-wk observational extension designed to investigate how ferric gluconate impacted epoetin dosage after DRIVE. During DRIVE-II, treating nephrologists and anemia managers adjusted doses of epoetin and intravenous iron as clinically indicated. By the end of observation, patients in the ferric gluconate group required significantly less epoetin than their DRIVE dose (mean change of -7527 +/- 18,021 IU/wk, P = 0.003), whereas the epoetin dose essentially did not change for patients in the control group (mean change of 649 +/- 19,987 IU/wk, P = 0.809). Mean hemoglobin, TSAT, and serum ferritin levels remained higher in the ferric gluconate group than in the control group (P = 0.062, P < 0.001, and P = 0.014, respectively). Over the entire 12-wk study period (DRIVE plus DRIVE-II), the control group experienced significantly more serious adverse events than the ferric gluconate group (incidence rate ratio = 1.73, P = 0.041). In conclusion, ferric gluconate maintains hemoglobin and allows lower epoetin doses in anemic hemodialysis patients with low TSAT and ferritin levels up to 1200 ng/ml.

Single-dosage pharmacokinetics of sodium ferric gluconate complex in iron-deficient pediatric hemodialysis patients.

BACKGROUND AND OBJECTIVES: The clinical use of sodium ferric gluconate complex in iron-deficient pediatric patients receiving hemodialysis was recently approved. This study was designed to describe the pharmacokinetic parameters of the medication. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Iron-deficient pediatric (< or = 15 yr) hemodialysis patients were randomly assigned to two doses (1.5 and 3.0 mg/kg) of sodium ferric gluconate complex. Blood samples taken during a 1-h infusion and at multiple intervals during 48 h were analyzed for total iron, transferrin-bound iron, and sodium ferric gluconate complex-bound iron. RESULTS: Forty-nine patients (mean age 12.3 +/- 2.5 yr) participated in the study. Mean serum iron concentrations rapidly increased in a dosage-dependent manner. A rapid rise in total serum iron was followed by a slower, less prominent rise in transferrin-bound iron. This was qualitatively confirmed by visualization of the transferrin bands from polyacrylamide gel electrophoresis. Single-dose pharmacokinetics of sodium ferric gluconate complex-bound iron was described using noncompartmental analytical methods. Mean values for the 1.5 mg/Kg dose were as follows: t(1/2) 2.0 +/- 0.7 h, Cmax 1287 mcg/dl, Tmax 1.1 +/- 0.23 h, Cl 0.69 +/- 0.50 L/h, Vd 1.6 +/- 0.6 L, AUC(0-infinity). 9499 +/- 4089 mcg x hr/dl. CONCLUSIONS: The infusion of sodium ferric gluconate complex to pediatric patients who receive hemodialysis appears to result in a delayed transfer of iron to transferrin, likely after an initial movement through the reticuloendothelial system. Differences noted between the pediatric and adult pharmacokinetic data may result from the unique aspects of the study populations and the respective study designs.

Intravenous ferric gluconate significantly improves response to epoetin alfa versus oral iron or no iron in anemic patients with cancer receiving chemotherapy.

PURPOSE: To evaluate the safety and efficacy of intravenous (IV) sodium ferric gluconate complex (FG), oral ferrous sulfate, or no iron to increase hemoglobin (Hb) in anemic cancer patients receiving chemotherapy and epoetin alfa. PATIENTS AND METHODS: In this open-label, multicenter trial, 187 patients with chemotherapy-related anemia (Hb <11 g/dl; serum ferritin > or =100 ng/ml or transferrin saturation > or =15%) scheduled to receive chemotherapy and epoetin alfa (40,000 U subcutaneously weekly) were randomized to 8 weeks of 125 mg of IV FG weekly, 325 mg of oral ferrous sulfate three times daily, or no iron. The primary outcome was a change in Hb from baseline to endpoint, first whole-blood or red blood cell transfusion, or study withdrawal. RESULTS: One hundred twenty-nine patients were evaluable for efficacy (FG, n = 41; oral iron, n = 44; no iron, n = 44). Mean increase in Hb was 2.4 g/dl (95% confidence interval [CI], 2.1-2.7) for FG (p = .0092 vs. oral iron; p = .0044 vs. no iron), 1.6 g/dl (95% CI, 1.1-2.1) for oral iron (p =.7695 vs. no iron), and 1.5 g/dl (95% CI, 1.1-1.9) for no iron. Hb response (increase > or =2 g/dl) was 73% for FG (p = .0099 vs. oral iron; p = .0029 vs. no iron), 46% for oral iron (p = .6687 vs. no iron), and 41% for no iron. FG was well tolerated. CONCLUSION: For cancer patients with chemotherapy-related anemia receiving epoetin alfa, FG produces a significantly greater increase in Hb and Hb response compared with oral iron or no iron, supporting more aggressive treatment with IV iron supplementation for these patients.

Ferric gluconate is highly efficacious in anemic hemodialysis patients with high serum ferritin and low transferrin saturation: results of the Dialysis Patients' Response to IV Iron with Elevated Ferritin (DRIVE) Study.

Few data exist to guide treatment of anemic hemodialysis patients with high ferritin and low transferrin saturation (TSAT). The Dialysis Patients' Response to IV Iron with Elevated Ferritin (DRIVE) trial was designed to evaluate the efficacy of intravenous ferric gluconate in such patients. Inclusion criteria were hemoglobin or=225 IU/kg per wk or >or=22,500 IU/wk. Patients with known infections or recent significant blood loss were excluded. Participants (n=134) were randomly assigned to no iron (control) or to ferric gluconate 125 mg intravenously with eight consecutive hemodialysis sessions (intravenous iron). At randomization, epoetin was increased 25% in both groups; further dosage changes were prohibited. At 6 wk, hemoglobin increased significantly more (P=0.028) in the intravenous iron group (1.6 +/- 1.3 g/dl) than in the control group (1.1 +/- 1.4 g/dl). Hemoglobin response occurred faster (P=0.035) and more patients responded after intravenous iron than in the control group (P=0.041). Ferritin 800 ng/ml had no relationship to the magnitude or likelihood of responsiveness to intravenous iron relative to the control group. Similarly, the superiority of intravenous iron compared with no iron was similar whether baseline TSAT was above or below the study median of 19%. Ferritin decreased in control subjects (-174 +/- 225 ng/ml) and increased after intravenous iron (173 +/- 272 ng/ml; P<0.001). Intravenous iron resulted in a greater increase in TSAT than in control subjects (7.5 +/- 7.4 versus 1.8 +/- 5.2%; P<0.001). Reticulocyte hemoglobin content fell only in control subjects, suggesting worsening iron deficiency. Administration of ferric gluconate (125 mg for eight treatments) is superior to no iron therapy in anemic dialysis patients receiving adequate epoetin dosages and have a ferritin 500 to 1200 ng/ml and TSAT