Common IV iron formulations and considerations for their use in adults with HHT
| Formulation . | Dose per infusion . | Time per infusion . | Suitability in HHT . | Clinical considerations . |
|---|---|---|---|---|
| Low molecular weight iron dextran | Weight- and hemoglobin-based dosing (label) 1000 mg (off-label, published data)26 | 1-4 h | Good | High quantity of iron may be safely administered in a single infusion (although this approach is off-label, it is widely applied) and safely repeated as necessary First infusion requires test dose (25 mg administered, followed by 1-h observation before full infusion may begin) Long infusion time can make scheduling difficult at busy infusion centers, inconvenient for patient |
| Iron sucrose | 200-400 mg (label∗) | 1.5-4 h | Suboptimal | Inconvenient, because it requires both high infusion frequency (3-5 infusions to administer the same amount of iron as other products can provide in a single infusion) and long infusion time (which can make scheduling difficult at busy infusion centers) |
| Ferric gluconate | 125 mg (label∗) 250 mg (off-label, published data)27 | 1-2 h | Suboptimal | Inconvenient, as it requires both high infusion frequency (3-5 infusions to administer the same amount of iron as other products can provide in a single infusion) and long infusion time (which can make scheduling difficult at busy infusion centers) Contains benzyl alcohol as a preservative; benzyl alcohol is an irritant and may cause hypersensitivity reactions, including local irritation and skin reaction in adults. Ferric gluconate is contraindicated in infants because it may cause a “gasping syndrome” that can be fatal; avoid in pregnant patients (it is not known whether benzyl alcohol crosses the placenta). |
| Ferumoxytol | 510 mg (label) 1020 mg (off-label, published data)28 | 15-30 minutes† | Ideal | High quantity of iron may be safely administered in a single infusion and safely repeated as necessary Avoid if MRI is planned within 3 months of infusion (interferes with interpretation). If MRI is necessary within 3 months of ferumoxytol administration, use T1- or proton-density–weighted MR pulse sequences to minimize the ferumoxytol effects on MRI images; MR imaging using T2-weighted pulse sequences should not be performed earlier than 4 weeks after administration. |
| Ferric carboxymaltose | 750 mg (label) | 15 min | Avoid | Unacceptably high rates (up to 75% in randomized controlled trials) of hypophosphatemia‡ which may last for weeks to months after a single infusion, resists repletion (results from acquired renal lesion so oral and IV phosphate supplements are promptly lost in the urine), and which may be severe and/or symptomatic after a single infusion. Repeat infusions as are often required in HHT may result in serious decline in bone density, bone demineralization/osteomalacia, and pathologic fractures or pseudofractures. Standard X-rays are insensitive to diagnosing pseudofractures, which require MRI to reliably diagnose Newer formulation, more expensive |
| Ferric derisomaltose | 1000 mg if ≥50 kg, 20 mg/kg if <50 kg (label) | 20 min | Ideal | High quantity of iron may be safely administered in a single infusion and safely repeated as necessary Much lower risk of hypophosphatemia (<4%) than ferric carboxymaltose Newer formulation, more expensive |
| Formulation . | Dose per infusion . | Time per infusion . | Suitability in HHT . | Clinical considerations . |
|---|---|---|---|---|
| Low molecular weight iron dextran | Weight- and hemoglobin-based dosing (label) 1000 mg (off-label, published data)26 | 1-4 h | Good | High quantity of iron may be safely administered in a single infusion (although this approach is off-label, it is widely applied) and safely repeated as necessary First infusion requires test dose (25 mg administered, followed by 1-h observation before full infusion may begin) Long infusion time can make scheduling difficult at busy infusion centers, inconvenient for patient |
| Iron sucrose | 200-400 mg (label∗) | 1.5-4 h | Suboptimal | Inconvenient, because it requires both high infusion frequency (3-5 infusions to administer the same amount of iron as other products can provide in a single infusion) and long infusion time (which can make scheduling difficult at busy infusion centers) |
| Ferric gluconate | 125 mg (label∗) 250 mg (off-label, published data)27 | 1-2 h | Suboptimal | Inconvenient, as it requires both high infusion frequency (3-5 infusions to administer the same amount of iron as other products can provide in a single infusion) and long infusion time (which can make scheduling difficult at busy infusion centers) Contains benzyl alcohol as a preservative; benzyl alcohol is an irritant and may cause hypersensitivity reactions, including local irritation and skin reaction in adults. Ferric gluconate is contraindicated in infants because it may cause a “gasping syndrome” that can be fatal; avoid in pregnant patients (it is not known whether benzyl alcohol crosses the placenta). |
| Ferumoxytol | 510 mg (label) 1020 mg (off-label, published data)28 | 15-30 minutes† | Ideal | High quantity of iron may be safely administered in a single infusion and safely repeated as necessary Avoid if MRI is planned within 3 months of infusion (interferes with interpretation). If MRI is necessary within 3 months of ferumoxytol administration, use T1- or proton-density–weighted MR pulse sequences to minimize the ferumoxytol effects on MRI images; MR imaging using T2-weighted pulse sequences should not be performed earlier than 4 weeks after administration. |
| Ferric carboxymaltose | 750 mg (label) | 15 min | Avoid | Unacceptably high rates (up to 75% in randomized controlled trials) of hypophosphatemia‡ which may last for weeks to months after a single infusion, resists repletion (results from acquired renal lesion so oral and IV phosphate supplements are promptly lost in the urine), and which may be severe and/or symptomatic after a single infusion. Repeat infusions as are often required in HHT may result in serious decline in bone density, bone demineralization/osteomalacia, and pathologic fractures or pseudofractures. Standard X-rays are insensitive to diagnosing pseudofractures, which require MRI to reliably diagnose Newer formulation, more expensive |
| Ferric derisomaltose | 1000 mg if ≥50 kg, 20 mg/kg if <50 kg (label) | 20 min | Ideal | High quantity of iron may be safely administered in a single infusion and safely repeated as necessary Much lower risk of hypophosphatemia (<4%) than ferric carboxymaltose Newer formulation, more expensive |
Licensed dosing and indications from US FDA labels; these may vary depending on country and licensing agency.
FDA, US Food and Drug Administration; MR, magnetic resonance; MRI, magnetic resonance imaging.
Iron sucrose and ferric gluconate are currently only indicated for the treatment of iron deficiency anemia in patients with chronic kidney disease, so use outside of patients with chronic kidney disease is off-label (although common).
Prior ferumoxytol FDA labeling recommended a 510-mg IV push over 17 seconds, which resulted in a high rate of infusion reactions. This led to revised US labeling for infusion over 15 minutes (and removal from the market in other countries). Administration over at least 15 minutes results in a much lower rate of hypersensitivity reactions (0.4%).
Updated FDA label additionally requires monitoring of serum phosphate in any patient “at risk for low serum phosphate” receiving repeat courses of treatment. Patients at risk for low serum phosphate include patients with a history of gastrointestinal disorders associated with malabsorption, concurrent or prior use of medications affecting renal proximal tubular function, hyperparathyroidism, vitamin D deficiency, chronic alcohol use, use of insulin, and malnutrition, among others. In randomized controlled trials of patients with typical iron deficiency anemia, however, rates of hypophosphatemia approached 75% with a typical 2-infusion series, so in reality all patients are at risk for developing hypophosphatemia. Although monitoring is indicated, there is no effective treatment for ferric carboxymaltose–induced renal phosphate wasting, which usually resolves spontaneously within 3 months of the ferric carboxymaltose infusion.