Dose Of Ferric Carboxymaltose Research Articles

A multicenter, randomized, active‐controlled study to investigate the efficacy and safety of intravenous ferric carboxymaltose in patients with iron deficiency anemia

Many patients receiving oral iron for iron deficiency anemia (IDA) cannot tolerate or fail to respond to therapy, and existing intravenous (IV) iron formulations often require repeated administrations. Ferric carboxymaltose (FCM), a nondextran IV formulation, permits larger single doses. We evaluated FCM versus oral iron in IDA patients. After 14 days of oral iron, 507 participants responding inadequately to oral iron (hemoglobin [Hb] increase <1 g/dL; Cohort 1) were assigned to Group A (two doses of FCM, 750 mg, 1 week apart) or Group B (oral iron, 325 mg, 3 × day for 14 additional days). Also, 504 subjects not appropriate for oral iron (Cohort 2) were assigned to Group C (FCM as above) or Group D (standard-of-care IV iron). The primary efficacy endpoint was change to highest observed Hb from baseline to Day 35. The composite safety endpoint included all-cause mortality, nonfatal myocardial infarction, nonfatal stroke, unstable angina, heart failure, arrhythmias, and hyper- or hypotensive events. Mean (± standard deviation [SD]) Hb increase was significantly greater in Group A-FCM than Group B-oral iron: 1.57 (±1.19) g/dL versus 0.80 (±0.80) g/dL (p = 0.001). Post hoc comparison of Group C-FCM and Group D-IV standard of care also demonstrated significant mean (±SD) increase in Hb from baseline to highest value by Day 35 in Group C versus Group D: 2.90 (±1.64) g/dL versus 2.16 (±1.25) g/dL (p = 0.001). Safety endpoints occurred in 17 of 499 (3.4%) participants receiving FCM versus 16 of 498 (3.2%) in comparator groups. Two 750-mg FCM infusions are safe and superior to oral iron in increasing Hb levels in IDA patients with inadequate oral iron response.

Acute and sub-acute effect of ferric carboxymaltose on inflammation and adhesion molecules in patients with predialysis chronic renal failure.

Treatment with parenteral iron causes oxidative stress, inflammation and endothelial dysfunction. Ferric carboxymaltose (FCM) is a new preparation of non-dextran iron which, due to its pharmacokinetics and stability, may induce less toxicity than other iron molecules. The aim of this study was to analyse the effect of FCM on inflammation and adhesion molecules in chronic kidney disease (CKD). Forty-seven patients with predialysis CKD and iron-deficiency anaemia received a single dose of FCM (15 mg/kg, maximum dose 1 gram). At baseline and after 60 minutes (acute effect) and after 3 weeks and 3 months (sub-acute effect), we determined inflammatory markers: C-reactive protein (CRP), interleukin-6 (IL-6) and endothelial dysfunction: intercellular adhesion molecule (ICAM) and vascular adhesion molecule (VCAM). Treatment with FCM was associated with a significant increase in haemoglobin levels: 10 (0.7) vs. 11.4 (1.3)g/dl, p<.0001. CRP, IL-6, ICAM and VCAM levels did not correlate with baseline haemoglobin or ferritin levels and there was no relationship between changes in these markers and those of haemoglobin after administration of FCM. No significant, acute or sub-acute changes occurred in any of the inflammatory or endothelial markers studied. Statin therapy was associated with lower VCAM concentrations. Treatment with high doses of FCM in patients with predialysis CKD has no proinflammatory effect and does not alter levels of adhesion molecules ICAM and VCAM in this population.

DGI-064 Study of the Use of Ferric Carboxymaltose (FC) Within the System For Preoperative Optimization of Haemoglobin (Hb) in Scheduled Surgery

BackgroundIn our hospital there is a protocol for preoperative Hb optimization with the aim of reducing blood transfusions in patients with anaemia and upcoming surgery.Purpose To evaluate the use of...

Intravenous ferric carboxymaltose versus standard medical care in the treatment of iron deficiency anemia in patients with chronic kidney disease: a randomized, active-controlled, multi-center study

Currently available intravenous (IV) iron agents vary in indication, dosing regimens and safety profiles. Ferric carboxymaltose (FCM) is a stable, non-dextran-containing iron formulation developed for rapid IV administration in high doses with controlled delivery of iron into target tissues. The objective of the present study was to evaluate the safety of FCM compared with standard medical care (SMC) in dialysis (HD) and non-dialysis-dependent (NDD) chronic kidney disease (CKD) patients. Adults 18-85 years of age with CKD were enrolled. NDD-CKD (n = 204) patients received an undiluted IV dose of FCM (15 mg/kg to a maximum of 1000 mg IV) and HD-CKD (n = 50) patients received an undiluted IV push of 200 mg ~30-60 min into the dialysis session. Subjects randomized to the SMC group (n = 259) received treatment determined by the investigator that could include oral iron, IV iron or no iron. Single doses of FCM of 200 mg in HD-CKD patients and up to 1000 mg in NDD-CKD patients were well tolerated. Incidences of treatment-emergent adverse events were similar between the groups: 30.3% (77 of 254) in the FCM group and 32.8% (85 of 259) in the SMC group. Incidences of serious adverse events were higher in the SMC group overall and in patients receiving iron sucrose or sodium ferric gluconate. There were no clinically significant differences in laboratory or clinical chemistry values or vital signs between the groups. There were no statistically significant differences between the FCM and SMC groups in indices of hemoglobin (Hb) improvement, including proportions of patients achieving a ≥ 1 g/dL increase in Hb and proportions of patients achieving Hb level of >12 g/dL. FCM in doses of 200 mg for HD-CKD patients and up to 1000 mg in NDD-CKD patients were well tolerated and displayed comparable efficacy to other IV iron formulations.

PMO-257 Cost-effectiveness and cost comparison of intravenous iron preparations in patients with IBD-associated iron deficiency anaemia based on the FERGImain trial

IntroductionAnaemia is a costly complication of IBD and a common trigger of hospitalisation. The FERGImain trial, a multi-centre, randomised, placebo-controlled study, demonstrated that on-demand ferric carboxymaltose (FCM) reduced recurrence of...

Safety and Efficacy of High Dose Intravenous Ferric Carboxymaltose vs. Standard Medical Care in the Treatment of Iron Deficiency Anemia

Purpose: This trial evaluates the safety and efficacy of intravenous (IV) Ferric Carboxymaltose (FCM) compared to standard medical care (SMC) in the management of iron deficiency anemia (IDA). Methods: FCM is a stable non-dextran iron compound developed for high dose rapid IV administration. Two open label, randomized controlled trials were conducted at 95 sites. In one, multiple doses of FCM were administered (md). In the other a single dose (sd) was given. Subjects with IDA were eligible if age 18-85 and not on dialysis, with hemoglobin (Hb) ≤ 12 g/dL, ferritin ≤100 ng/mL, and transferrin ≤30%. Subjects were randomized in a 1:1 ratio to receive FCM or SMC (oral or IV iron or no iron). In the md study, subjects in the FCM group got 750 mg (15 mg/kg) undiluted @ 100 mg/min weekly in order to replenish their iron deficit (calculated by the Ganzoni formula) up to 2250 mg total. Subjects in the sd trial got one injection of FCM, 750 mg @ 100 mg/min. Results: Enrollment in the md study was: 343-FCM, 360-SMC; in the sd study it was: 366-FCM, 369-SMC. There was a significantly greater increase in Hb, hematocrit, and ferritin from baseline to Day 30 observed with FCM compared to SMC (p ≤ 0.001). The overall adverse event (AE) rate was similar in both studies. The most frequent AEs were constipation, diarrhea, nausea, vomiting, abdominal pain, dizziness, and headache. More vomiting and constipation were noted in the SMC group. Low serum phosphate values were frequently observed after FCM treatment (48% in md), but were not associated with other clinical sequelae. There was 1 drug-related serious AE in the FCM group (constipation) and 2 in the SMC group (renal infarct, hypotension). Other serious adverse events occurred equally in the two groups. There was 1 death in the SMC group (pneumonia). There were no serious hypersensitivity reactions or deaths in the FCM group. Conclusion: IV iron is often preferred for treating IDA associated with renal disease, bleeding, poor absorption (gastric bypass or Celiac disease) or oral intolerance. There is an unmet need for safe IV iron available in large single doses. Iron dextrans are associated with a substantial risk of fatal anaphylaxis (and high doses are not FDA approved). The available non-dextran irons must also be administered in low doses (usually ≤ 200 mg) necessitating multiple visits. This study demonstrated that FCM and SMC both replenish iron. FCM was well tolerated with similar AE rates in the FCM and SMC groups. The majority of AEs were not severe; there were no deaths in the FCM group. FCM may be safely administered at high dose in an outpatient setting taking < 10 min per dose, requiring fewer clinic visits and fewer venipunctures. Disclosure: Luitpold Pharmaceuticals Dr. Barish - Investigator research support, Dr. Bregman - Medical Director, Luitpold Ms. Butcher - Project Manager, Luitpold, Mr. Koch - Project Manager, Luitpold., Dr. Morris - Statistician, Luitpold. This research was supported by an industry grant from Luitpold Pharmaceuticals.

Clinical experience with ferric carboxymaltose as treatment of cancer-associated anemia.

e19561 Background: Controlled studies showed that intravenous iron can improve hemoglobin (Hb) levels and decrease the need for erythropoiesis-stimulating agents (ESAs) and blood transfusions in anemic cancer patients. This observational study provides data on effectiveness and safety of ferric carboxymaltose (FCM) in routine treatment of anemia in cancer patients. Methods: 642 cancer patients (≥18 years) with iron deficiency anemia were registered from Dec 2008 to Jul 2010 at 73 German hematology/oncology practices. FCM was administered without restriction on dose and concomitant ESA or blood transfusion use. This interim analysis assessed safety in 581 patients receiving at least one FCM dose, and evaluable Hb difference (effectiveness) in those also completing the study by August 2010 (n=401). Results: Patients (mean age 64 years; male 49%) mainly presented with solid tumors (90%) and received cytotoxic chemotherapy (72%); 20.9% were previously treated for anemia. Mean total iron dose per patient was 1,333 mg; 15.7% received also an ESA and 25.6% a blood transfusion. Mean Hb increased within 5 weeks and remained between 11–12 g/dL until the end of the 12-week study period (Table). Benefit was comparable in patients with mild and moderate-severe anemia. Hb also improved comparably in patients treated with FCM alone or with concomitant ESAs. FCM treatment was well tolerated. Possibly or probably drug-related adverse events (AEs), mainly nausea and diarrhea, were reported for 2.4% of patients. Two fatal cases occurred: one of unknown cause and unrelated to FCM and one after a possibly related respiratory insufficiency. Two serious AEs (tachycardia, dyspnea) were unlikely related to FCM. Conclusions: Hb of FCM-treated anemic cancer patients effectively stabilized at 11–12 g/dL independent of baseline Hb levels and concomitant erythropoietic therapy. This observational study suggests FCM is beneficial as anemia treatment in cancer patients. Hb at baseline (BL) and increase to Wk 5 and Wk 12 (g/dL). Patients (n) BL* DHb to Wk 5+ DHb to Wk 12+ All (401) 10.0 ± 1.4 1.0 1.4 BL Hb <10 g/dL (206) 9.0 ± 0.9 1.7 2.2 BL Hb 10-11 g/dL (116) 10.4 ± 0.3 0.7 1.1 FCM only (345) 10.1 ± 1.4 1.0 1.4 FCM + ESA (56) 9.4 ± 1.2 1.4 1.5 * Mean ± SD. + Difference of means vs BL.

Safety and tolerability of intravenous ferric carboxymaltose in patients with iron deficiency anemia

There is limited safety information about ferric carboxymaltose (FCM), a new intravenous iron preparation. This randomized, crossover study compared the safety and tolerability of double-blinded intravenous doses of FCM or placebo in patients with iron deficiency anemia. Subjects (559) with iron deficiency anemia received a dose of either FCM (15 mg/kg, maximum 1000 mg) over 15 minutes or placebo on day 0. On day 7, subjects received the other agent. Safety evaluations were performed on days 7 and 14. The primary endpoint was the incidence of treatment-emergent adverse events during each 7-day study period. During the first 24 hours and during the 7-day treatment period, at least one treatment-emergent adverse event was experienced by 15.0% and 29.3% of subjects after FCM and 11.4% and 19.7% after placebo, respectively. Most were classified as Grade 1 or 2. Six subjects had Grade 3 treatment-emergent adverse events after FCM and 9 subjects after placebo. One subject had a Grade 4, and 1 subject had a Grade 5 treatment-emergent adverse event, but neither was considered study drug-related. During the first 24 hours of the treatment period, drug-related adverse events were reported in 9.3% of subjects receiving FCM and 4.8% receiving placebo. Of drug-related Grade 3 events, 4 subjects received FCM and 5 subjects received placebo. Administration of FCM (15 mg/kg, maximum of 1000 mg) over 15 minutes was well tolerated and associated with minimal risk of adverse reactions in patients with iron deficiency anemia.

55: Treating postpartum anemia with intravenous ferric carboxymaltose in a randomized controlled study

A RANDOMIZED CONTROLLED STUDY MELVIN H. SEID, RALPH ROGERS, QUINN DINH, Lyndhurst Gynecologic Associates, Winston Salem, North Carolina, Women’s Clinical Research, Newburgh, Indiana, American Regent/Luitpold Pharmaceuticals, Norristown, Pennsylvania OBJECTIVE: To evaluate the superiority, safety and tolerability of ferric carboxymaltose (FCM) to oral iron in postpartum women with iron deficiency anemia (IDA). FCM is a novel non-dextran iron agent given in large doses by rapid IV injection. STUDY DESIGN: In a randomized, controlled, superiority designed pivotal trial, 289 women 10 days post-delivery with hemoglobin 10g/dL were randomized and received: (a) FCM up to 1,000mg IV over 15 minutes, repeated weekly to correct anemia up to maximum total calculated dose of 2,500mg, or (b) Oral ferrous sulfate 325mg (65mg elemental iron) thrice daily for 6 weeks. RESULTS: Patients (n 142) received 293 IV doses of FCM (mean total dose 1504mg) in 1, 2, or 3 injection(s) [5%, 84%, or 11% respectively]; 147 received oral iron. FCM group compared with oral iron group was: (1) more likely to achieve hemoglobin (Hb) 12g/dL (91% vs. 67%, p .0001) in a shorter time period (14 days vs. 27 days, p .0002) with sustained success (85% vs. 58%) at Day 42, (p .0001), (2) more likely to achieve Hb rise 3.0g/dL at any time (91% vs. 65%, p .0001) in a shorter time period (15 days vs. 28 days, p .0001), and (3) more likely to attain higher transferrin saturation (TSAT) (36% vs. 28%) and ferritin (647 ng/mL vs. 12 ng/mL), p .0001. Drug-related adverse events (AEs) were lower with FCM (11%) than oral iron (22%). Urticaria (2%) was the only drug-related AE occurring in 2% of the FCM group. Constipation (11%;0%), elevated ALT (4%; 0.7%), elevated AST (2%;0.7%), and nausea (2%;1.4%) were more common with oral iron than FCM, respectively. No hypotensive or drug-related serious AEs such as hypersensitivity or anaphylactic reactions were reported in either treatment group. CONCLUSION: Ferric carboxymaltose (FCM) was safe and well-tolerated. FCM was superior to oral iron in increasing Hb 12g/dL earlier with greater sustained success. FCM was more effective in raising TSAT and ferritin. This non-dextran IV iron agent may fulfill an unmet medical need for safe, rapid administration of iron in single doses up to 1,000mg in postpartum women with IDA.