Ferric Carboxymaltose Group Research Articles

Safety and Efficacy of Intravenous Ferric Carboxymaltose (750 mg) in the Treatment of Iron Deficiency Anemia: Two Randomized, Controlled Trials

Background. Iron deficiency anemia (IDA) is a common hematological complication with potentially serious clinical consequences that may require intravenous iron therapy. Ferric carboxymaltose (FCM) is a stable, nondextran iron formulation administered intravenously in large single doses to treat IDA. Objective. Two open-label, randomized, placebo-controlled trials evaluated safety of multiple or single 750 mg FCM doses compared to standard medical care (SMC) in IDA patients. Secondary endpoints were improvements in hemoglobin and iron indices. Design and Patients. Adults with hemoglobin ≤12 g/dL, ferritin ≤100 or ≤300 ng/mL with transferrin saturation ≤30% were randomized to receive single (n = 366) or weekly (n = 343) FCM or SMC (n = 360 and n = 366). Results. Significantly greater (P ≤ 0.001) increases in hemoglobin and iron indices occurred in FCM groups versus SMC. In the multidose study, up to two infusions of FCM were needed to reach target iron levels versus 3–5 of intravenous iron comparators. FCM and SMC groups had similar incidences and types of adverse events and serious adverse events. Transient hypophosphatemia not associated with adverse events or clinical sequelae occurred in the FCM groups. Conclusion. Intravenous FCM is safe, well tolerated, and associated with improvements in hemoglobin and iron indices comparable to SMC when administered in single doses of up to 750 mg at a rate of 100 mg/min. Fewer FCM infusions were required to reach target iron levels compared to other intravenous iron preparations.

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.

Comparison of the renal, cardiovascular and hepatic toxicity data of original intravenous iron compounds

Intravenous (i.v.) iron is essential for managing haemoglobin levels in haemodialysis patients. However, i.v. iron may cause variable degrees of toxicity. This is mainly related to the pharmacological characteristics of any given i.v. iron compound. This blinded study examines the effects of five i.v. iron preparations on haemodynamic and functional parameters. Sixty Sprague-Dawley rats (n = 10/group) received high or low molecular weight (HMW/LMW) iron dextran, ferric gluconate (FG), ferric carboxymaltose (FCM), iron sucrose (ISC) or isotonic saline solution (control). Five i.v. doses of iron (40 mg iron/kg) or saline were administered over 4 weeks. Systolic blood pressure was significantly reduced in the LMW dextran group, whereas serum iron and percentage transferrin saturation were significantly elevated in all treatment groups. Creatinine clearance was reduced and urinary protein excretion increased in the FG group only (P < 0.01). Liver enzyme levels in the blood were increased (P < 0.01) in the FG and two dextran groups compared with the FCM and ISC groups. Analysis of liver, heart and kidney homogenates showed a significant increase in catalase and malondialdehyde levels in the FG group, and an increase in CuZn-superoxide dismutase and glutathione (GSH) peroxidase activity accompanied with a decrease in the reduced-to-oxidized GSH ratio in the FG and two dextran groups (P < 0.01). Tumour necrosis factor alpha and interleukin-6 levels were significantly elevated in liver, heart and kidney samples from the FG and two dextran groups but not the FCM, ISC or control groups. These findings indicate that FG and HMW/LMW iron dextran have less favourable safety profiles than FCM and ISC in normal rats.

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.