Table 1.

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

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