Introduction
Injectafer (ferric carboxymaltose) is an intravenous iron replacement therapy indicated for the treatment of iron deficiency anemia in adult patients who have intolerance or unsatisfactory response to oral iron therapy. It represents an important therapeutic option for patients requiring rapid iron repletion or those with conditions that impair oral iron absorption.
Mechanism of Action
Ferric carboxymaltose is a complex of ferric hydroxide and carboxymaltose, a carbohydrate polymer that allows for controlled delivery of iron to iron-binding proteins. The complex is taken up by the reticuloendothelial system, where iron is released from the carbohydrate shell and incorporated into hemoglobin, ferritin, and other iron storage proteins. The carboxymaltose shell minimizes free iron toxicity by preventing rapid release of ionic iron into the circulation.
Indications
- Treatment of iron deficiency anemia in adults who have intolerance to oral iron or have had unsatisfactory response to oral iron
- Treatment of iron deficiency anemia in adult patients with non-dialysis dependent chronic kidney disease
Dosage and Administration
Standard dosing:- Administer by intravenous infusion over at least 15 minutes
- Total cumulative dose: 15 mg/kg of body weight or maximum of 1000 mg per course
- May be repeated if iron deficiency anemia recurs
- Renal impairment: No dosage adjustment necessary
- Hepatic impairment: Use with caution; limited data available
- Elderly: No dosage adjustment necessary
- Pregnancy: Category C - use only if potential benefit justifies potential risk
Pharmacokinetics
Absorption: Administered intravenously, achieving 100% bioavailability Distribution: Volume of distribution approximately 7.9 L; binds to transferrin and ferritin Metabolism: Iron is incorporated into hemoglobin and iron storage proteins Elimination: Minimal renal excretion; primarily eliminated via reticuloendothelial system processing with eventual loss through desquamation of epithelial cells and minor losses in sweat, bile, and urineContraindications
- Hypersensitivity to ferric carboxymaltose or any component of the formulation
- Patients with evidence of iron overload
- Patients with anemia not caused by iron deficiency
Warnings and Precautions
Hypersensitivity reactions: Serious hypersensitivity reactions, including anaphylaxis, have been reported. Monitor patients for signs during and for at least 30 minutes after infusion. Hypotension: May cause clinically significant hypotension. Monitor blood pressure during administration. Iron overload: Excessive dosages may lead to hemosiderosis and potential organ damage. Compromised antioxidant capacity: May increase risk of bacterial infections as iron is essential for bacterial growth.Drug Interactions
- Dimercaprol: Avoid concurrent use as it may form toxic complexes with iron
- Oral iron preparations: May reduce absorption of oral iron; separate administration by at least 24 hours
- ACE inhibitors: May potentiate hypotensive effects
- Chloramphenicol: May delay iron utilization
Adverse Effects
Common (≥1%):- Nausea (3.3%)
- Headache (2.5%)
- Dizziness (2.1%)
- Hypertension (1.8%)
- Flushing (1.7%)
- Injection site reactions (1.5%)
- Anaphylaxis (0.1%)
- Severe hypotension
- Hypophosphatemia (may occur in up to 38% of patients; usually asymptomatic and self-limiting)
Monitoring Parameters
- Hemoglobin, hematocrit, iron parameters (ferritin, transferrin saturation) at baseline and 4 weeks post-infusion
- Vital signs before, during, and for 30 minutes after infusion
- Signs and symptoms of hypersensitivity reactions
- Serum phosphate levels (monitor for hypophosphatemia)
- Blood pressure during administration
Patient Education
- Inform patients about potential side effects, including flushing, nausea, and dizziness
- Advise patients to report any signs of allergic reaction (rash, itching, swelling, difficulty breathing) immediately
- Explain that urine may darken for a day or two after administration (normal phenomenon)
- Inform patients that improvement in anemia symptoms may take several weeks
- Advise patients not to take oral iron supplements unless directed by their healthcare provider
- Encourage reporting of any persistent muscle weakness, bone pain, or unusual fatigue
References
1. Injectafer [package insert]. Shirley, NY: American Regent, Inc.; 2020. 2. Auerbach M, Ballard H. Clinical use of intravenous iron: administration, efficacy, and safety. Hematology Am Soc Hematol Educ Program. 2010;2010:338-347. 3. Onken JE, Bregman DB, Harrington RA, et al. Ferric carboxymaltose in patients with iron deficiency anemia and impaired iron absorption. Ther Adv Chronic Dis. 2014;5(2):70-83. 4. Macdougall IC, Bock AH, Carrera F, et al. FIND-CKD: a randomized trial of intravenous ferric carboxymaltose versus oral iron in patients with chronic kidney disease and iron deficiency anaemia. Nephrol Dial Transplant. 2014;29(11):2075-2084. 5. FDA-approved labeling for Injectafer. Accessed through DailyMed.