IV iron preparations available for clinical use in United States and Europe
| Iron preparation . | Maximal single dose in adults* . | Administration in adults* . | Indications in adults* . | Most common adverse effects in adults* . | Evaluated in HF†‡ . |
|---|---|---|---|---|---|
| FCM | 750 mg | Slow IV push @ 100 mg/min, or diluted in normal saline and infused over at least 15 min | Treatment of ID anemia in adult patients who have intolerance to oral iron or have had unsatisfactory response to oral iron, or those who have nondialysis-dependent CKD | Nausea, hypertension, flushing, hypophosphatemia, and dizziness | Yes |
| Can be repeated at least 7 d later for a maximal total dose of 1500 mg per course | Warnings: hypersensitivity reactions, hypertension | Several currently ongoing trials in HFrEF and HFpEF | |||
| Courses can be repeated if ID recurs | |||||
| Iron sucrose | 100 to 400 mg, depending on clinical setting. Limited experience with 500 mg | Slow IV injection of 100 to 200 mg over 2 to 5 min | Treatment of ID anemia in patients with CKD | Diarrhea, nausea, vomiting, headache, dizziness, hypotension, pruritus, pain in extremity, arthralgia, back pain, muscle cramp, injection site reactions, chest pain, and peripheral edema | Yes |
| Doses can be repeated at varying intervals, depending on setting. Courses can be repeated if ID recurs | Infusion of 100 to 200 mg diluted in normal saline and infused over 15 min | Warnings: hypersensitivity reactions, hypotension, iron overload | No currently ongoing trials in HF | ||
| Infusion of 300 to 400 mg diluted in normal saline and infused over 1.5 to 2.5 h | |||||
| Iron isomaltoside§ | 20 mg/kg, to a maximum of 1500 mg | IV injection of up to 500 mg @ 250 mg/min, up to once a week | Treatment of ID in adults who have intolerance or lack of response to oral iron | Headache, nasopharyngitis, nausea, vomiting, and constipation | Yes‖ |
| Cumulative dose based on Ganzoni formula | Infusion: diluted in normal saline and infused over 20 min (dose ≤1000 mg) or 30 min (dose >1000 mg) | Not recommended for age <18 y | Special warnings and precautions: Hypersensitivity reactions including serious and potentially fatal anaphylactic/anaphylactoid reactions | Ongoing trials: IRONMAN (NCT02642562) in HFrEF. Primary outcome: cardiovascular mortality or HF hospitalization | |
| Administer with caution/avoid in patients with liver dysfunction or acute/chronic infection. Hypotension if infused too rapidly | FERRIC-HF III (UK). Primary outcome: cardiac energetics | ||||
| Injection site irritation or discoloration with leakage | |||||
| Sodium ferric gluconate | 125 mg (adults) | Adults: slow IV injection @ 12.5 mg/min, or diluted in normal saline and infused over 1 h per dialysis | Treatment of ID anemia in adult patients and in pediatric patients age 6 y and older with CKD receiving hemodialysis who are receiving supplemental erythropoietin therapy | Nausea, vomiting, and/or diarrhea, injection site reaction, hypotension, cramps, hypertension, dizziness, dyspnea, chest pain, leg cramps, and pain. In patients 6 to 15 y of age: hypotension, headache, hypertension, tachycardia, and vomiting | No |
| 1.5 mg/kg (pediatric patients) | Pediatric patients: dose diluted in normal saline and infused over 1 h per dialysis | Warnings: hypersensitivity, hypotension, iron overload, benzyl alcohol toxicity | Current trial in acute decompensated HF (NCT04063033) | ||
| Ferumoxytol | 510 mg | Diluted in normal saline or 5% dextrose and infused over at least 15 min | Treatment of ID anemia in adults with intolerance or unsatisfactory response to oral iron, or who have CKD | Diarrhea, headache, nausea, dizziness, hypotension, constipation, and peripheral edema | No |
| Second 510 mg dose 3 to 8 d later | Black Box warning: Fatal and serious hypersensitivity reactions, including anaphylaxis | No currently ongoing trials in HF | |||
| Iron dextran | 100 mg daily | Slow IV injection not to exceed 50 mg/min | Treatment of ID anemia when oral administration is unsatisfactory or impossible | Most common side effects not separately listed in the label | No |
| Total dose calculated based on body iron deficit | Black Box warning: Fatal and serious hypersensitivity reactions, including anaphylaxis | No currently ongoing trials in HF |
| Iron preparation . | Maximal single dose in adults* . | Administration in adults* . | Indications in adults* . | Most common adverse effects in adults* . | Evaluated in HF†‡ . |
|---|---|---|---|---|---|
| FCM | 750 mg | Slow IV push @ 100 mg/min, or diluted in normal saline and infused over at least 15 min | Treatment of ID anemia in adult patients who have intolerance to oral iron or have had unsatisfactory response to oral iron, or those who have nondialysis-dependent CKD | Nausea, hypertension, flushing, hypophosphatemia, and dizziness | Yes |
| Can be repeated at least 7 d later for a maximal total dose of 1500 mg per course | Warnings: hypersensitivity reactions, hypertension | Several currently ongoing trials in HFrEF and HFpEF | |||
| Courses can be repeated if ID recurs | |||||
| Iron sucrose | 100 to 400 mg, depending on clinical setting. Limited experience with 500 mg | Slow IV injection of 100 to 200 mg over 2 to 5 min | Treatment of ID anemia in patients with CKD | Diarrhea, nausea, vomiting, headache, dizziness, hypotension, pruritus, pain in extremity, arthralgia, back pain, muscle cramp, injection site reactions, chest pain, and peripheral edema | Yes |
| Doses can be repeated at varying intervals, depending on setting. Courses can be repeated if ID recurs | Infusion of 100 to 200 mg diluted in normal saline and infused over 15 min | Warnings: hypersensitivity reactions, hypotension, iron overload | No currently ongoing trials in HF | ||
| Infusion of 300 to 400 mg diluted in normal saline and infused over 1.5 to 2.5 h | |||||
| Iron isomaltoside§ | 20 mg/kg, to a maximum of 1500 mg | IV injection of up to 500 mg @ 250 mg/min, up to once a week | Treatment of ID in adults who have intolerance or lack of response to oral iron | Headache, nasopharyngitis, nausea, vomiting, and constipation | Yes‖ |
| Cumulative dose based on Ganzoni formula | Infusion: diluted in normal saline and infused over 20 min (dose ≤1000 mg) or 30 min (dose >1000 mg) | Not recommended for age <18 y | Special warnings and precautions: Hypersensitivity reactions including serious and potentially fatal anaphylactic/anaphylactoid reactions | Ongoing trials: IRONMAN (NCT02642562) in HFrEF. Primary outcome: cardiovascular mortality or HF hospitalization | |
| Administer with caution/avoid in patients with liver dysfunction or acute/chronic infection. Hypotension if infused too rapidly | FERRIC-HF III (UK). Primary outcome: cardiac energetics | ||||
| Injection site irritation or discoloration with leakage | |||||
| Sodium ferric gluconate | 125 mg (adults) | Adults: slow IV injection @ 12.5 mg/min, or diluted in normal saline and infused over 1 h per dialysis | Treatment of ID anemia in adult patients and in pediatric patients age 6 y and older with CKD receiving hemodialysis who are receiving supplemental erythropoietin therapy | Nausea, vomiting, and/or diarrhea, injection site reaction, hypotension, cramps, hypertension, dizziness, dyspnea, chest pain, leg cramps, and pain. In patients 6 to 15 y of age: hypotension, headache, hypertension, tachycardia, and vomiting | No |
| 1.5 mg/kg (pediatric patients) | Pediatric patients: dose diluted in normal saline and infused over 1 h per dialysis | Warnings: hypersensitivity, hypotension, iron overload, benzyl alcohol toxicity | Current trial in acute decompensated HF (NCT04063033) | ||
| Ferumoxytol | 510 mg | Diluted in normal saline or 5% dextrose and infused over at least 15 min | Treatment of ID anemia in adults with intolerance or unsatisfactory response to oral iron, or who have CKD | Diarrhea, headache, nausea, dizziness, hypotension, constipation, and peripheral edema | No |
| Second 510 mg dose 3 to 8 d later | Black Box warning: Fatal and serious hypersensitivity reactions, including anaphylaxis | No currently ongoing trials in HF | |||
| Iron dextran | 100 mg daily | Slow IV injection not to exceed 50 mg/min | Treatment of ID anemia when oral administration is unsatisfactory or impossible | Most common side effects not separately listed in the label | No |
| Total dose calculated based on body iron deficit | Black Box warning: Fatal and serious hypersensitivity reactions, including anaphylaxis | No currently ongoing trials in HF |
Adapted from Anand and Gupta1 with permission.
According to the regulatory agency–approved drug label at the time of writing of this article. Providers should check the latest drug information for changes, updates, and details prior to administration. There are several potential advantages of IV vs oral iron: It can be administered in one or a few doses; it rapidly restores iron stores even in the presence of inflammatory conditions; it causes less gastrointestinal side effects; and it does not depend on patient adherence/compliance. However, IV iron preparations are considerably more expensive, require facilities equipped for cardiopulmonary resuscitation since they can cause potentially fatal hypersensitivity reactions and other adverse effects, and can cause iron overload if not appropriately monitored.
All IV iron preparations appear to be equally safe and effective for replacement of ID in general, particularly at lower doses (reviewed in detail by Shehata et al61 ). For single infusions of larger doses (for replacement of total iron deficit), FCM, iron isomaltoside, and ferumoxytol can be used because they release the lowest levels (≤1%) of potentially toxic labile iron, have carbohydrate shells with reduced immunogenic potential, and do not require administration of test doses.62 The total body iron deficit (total iron dose required) can be estimated using the Ganzoni formula (body weight × [15 − Hb] × 2.4 + iron stores).63 An analysis of 7 studies found that the actual average total iron deficit is ∼1400 to 1500 mg in adults with ID anemia,64 and the average total iron deficit in patients with HFrEF is ∼1300 mg.46 In a large proportion of patients, therefore, the recommended single maximum dose of iron isomaltoside (1500 mg) will allow replacement of the total iron deficit in a single treatment.62 In patients with HFeEF, the highest level of evidence is available for the use of FCM.31,43,44 However, in practice, selection of the specific iron preparation to be used for correction of ID, its dose, and frequency of administration is usually determined by drug availability and cost, the product label, local protocol, indication for treatment, and patient convenience. Adequacy of replacement is assessed by improvement in Hb, ferritin, and TSAT.
Trials searched on www.ClinicalTrials.gov and www.clinicaltrialsregister.eu (accessed on October 14, 2019).
Approved in Europe and Canada but not in the United States. Drug information for iron isomaltoside obtained from www.pfizermedicalinformation.ca (accessed on October 14, 2019).
A small randomized, double-blind trial of iron isomaltoside vs placebo in patients with HFrEF (FERRIC-HF II) recently reported that iron isomaltoside significantly improved skeletal muscle energetics, iron parameters, NHYA class, resting respiratory rate, and postexercise Borg dyspnea score at 2 wk.26