Safety Profile of Iron Carboxymaltose, a New High Dose Intravenous Iron in Patients with Iron Deficiency Anemia. (2006)

Abstract Currently available IV iron agents pose substantial safety and practical challenges to effective management of iron deficiency anemia. Iron dextran administration requires a test dose and carries the risk of anaphylaxis. Non-dextran-containing IV iron agents (iron sucrose and ferric gluconate) do not require a test dose nor have this safety issue, but pose some practical challenges. These agents are FDA approved only for chronic kidney disease indications and require repeated administration of small doses (125 mg of iron as ferric gluconate over 10 minutes, 200 mg of iron as iron sucrose over 2–5 minutes, or 300–400 mg of iron as iron sucrose over 1.5 to 2.5 h). Accordingly, in a multicenter, randomized, blinded, placebo-controlled, crossover trial we assessed the safety of iron carboxymaltose, a new, investigational non-dextran IV iron complex that allows for rapid administration of high doses of iron. Five-hundred and eighty four (584) iron deficiency anemia patients received either a blinded dose of IV iron carboxymaltose (15 mg/kg up to a maximum of 1000 mg in NS) or placebo over 15 minutes on Day 0. On Day 7, patients were crossed over to receive either placebo or iron carboxymaltose utilizing the same dosing as Day 0. We recorded all adverse events and classified as an adverse drug event (ADE) any that was considered by the investigator as being possibly or probably related to study drug. The mean dose of iron carboxymaltose administered was 962 (+ 88) mg. No CTC Grade 4 or 5 or serious ADE were reported and no subject discontinued from study drug due to an ADE. No clinically important differences in vital signs or physical exams were noted between subjects treated with iron carboxymaltose and placebo. During the post dose 24-h and 7-d treatment period, ADEs reported by >1% of patients in either treatment were higher in patients after receiving iron carboxymaltose than in patients after receiving placebo. The 24-h period events included nausea (2.1% iron carboxymaltose vs. 1.1% placebo), headache (2.0% vs. 1.3%), and dizziness (1.3% vs. 0.2%). The 7-d period events included nausea (2.5% iron carboxymaltose vs. 1.1% placebo), ALT increased (1.3% vs. 0.2%), AST increased (1.3% vs. 0%), headache (2.9% vs. 1.4%), dizziness (1.6% vs.0.2%) and rash (1.1% vs. 0.2%). The majority of the ADEs were classified by the investigator as mild to moderate. No ADE consistent with a hypersensitivity reaction was reported. One patient experienced a transient, asymptomatic, CTC Grade 1 decrease in BP (from 132/85 to 95/68 mmHg) which resolved spontaneously. CTC Grade 3 ADEs were reported in 4 patients after receiving iron carboxymaltose (headache and asymptomatic decrease in serum phosphate) and 5 patients (rash, creatinine increase and asymptomatic decrease in serum phosphate) after receiving placebo. We conclude that rapid administration of high dose iron carboxymaltose (15 mg/kg for maximum of a 1,000 mg over 15 minutes) is well tolerated and associated with minimal risk of ADE in a large cohort of patients with iron deficiency anemia.