Note: Route of administration: IV iron replacement is preferred over oral replacement in several clinical situations (eg, poor GI absorption, lack of response to or poor tolerability of oral iron, need for rapid repletion, chronic kidney disease, active inflammatory bowel disease, cancer, chronic or extensive blood loss) (Auerbach 2021). Dosage expression: Dose is expressed in mg of elemental iron. Test dose: A test dose is not required.
Abdominal surgery, major (perioperative anemia management) (off-label use): IV: 15 mg/kg prior to surgery; maximum dose: 1,000 mg. Postoperatively (within 2 days of surgery), patients received 0.5 mg ferric carboxymaltose per 1 mL of blood loss (if blood loss was at least 100 mL) (Froessler 2016).
Chemotherapy-associated anemia (off-label use): IV: 1,000 mg (range: 600 to 1,500 mg) (Steinmetz 2013); consider dividing larger doses to a maximum single dose of 750 mg and separate by 7 days.
Iron-deficiency anemia , treatment:
≥50 kg:
Two-dose regimen: IV: 750 mg once; after ≥7 days, administer a second dose of 750 mg once; maximum dose: 1.5 g per treatment course.
Single-dose regimen: IV: 15 mg/kg as a single dose; maximum dose: 1 g.
<50 kg: IV: 15 mg/kg once; after ≥7 days, administer a second dose of 15 mg/kg once.
Iron-deficiency anemia in inflammatory bowel disease (off-label use): IV: 500 or 1,000 mg/dose on day 1 (and if needed based on hemoglobin values, days 8 and 15); patients <67 kg received a maximum of 500 mg per infusion (Evstatiev 2011)
Iron deficiency in heart failure with reduced ejection fraction (off-label use): Note: Patients may or may not be anemic. Iron deficiency in clinical trials was defined as a serum ferritin level <100 mcg/L or a serum ferritin level of 100 to 300 mcg/L if transferrin saturation is <20% (Anker 2009; Ponikowski 2015; Ponikowski 2020).
IV: 200 mg once weekly (until iron repletion is achieved), and then 200 mg once every 4 weeks during maintenance (starting at week 8 or 12, depending on the required iron-repletion dose) (Anker 2009) or 500 or 1,000 mg/dose at baseline and week 6, followed by 500 mg/dose at weeks 12, 24, and 36 if iron deficiency is still present (dose based on screening weight and hemoglobin values; refer to protocol for specific details) (Ponikowski 2015; Ponikowski 2020).
Restless legs syndrome (off-label use):
Note: For use as an alternative to oral iron repletion for patients with malabsorption, intolerance or lack of response to oral therapy, or need for rapid response to therapy; not recommended for initiation of therapy in patients with serum ferritin >100 mcg/L or transferrin saturation (TSAT) ≥45% (Allen 2018).
IV: 1 g as a single dose. May repeat at least 12 weeks after initial infusion based on initial response, recurrence of restless legs syndrome symptoms, and if serum ferritin <300 mcg/L and TSAT <45% (Allen 2018).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Chronic kidney disease, nondialysis dependent: No dosage adjustment necessary (indicated for use in nondialysis CKD)
There are no dosage adjustments provided in the manufacturer's labeling.
(For additional information see "Ferric carboxymaltose: Pediatric drug information")
Iron-deficiency anemia, treatment:
Children and Adolescents:
Two-dose regimen: IV: 15 mg/kg/dose for 2 doses separated by ≥7 days; maximum dose: 750 mg/dose (manufacturer's labeling).
Single- dose regimen: Limited data available: IV: 15 to 20 mg/kg/dose as a single dose; maximum dose: 1,000 mg/dose (Carman 2019; Powers 2017; Sasankan 2021; Tan 2017). Dosing based on calculated iron deficit using the Ganzoni equation has also been reported; reported doses range from 10 to 32 mg/kg/dose with maximum single doses of 1,000 mg/dose (Laass 2014; Ozsahin 2020; Papadopoulos 2018; Tan 2017; UK product labeling).
Restless sleep disorder: Very limited data available: Children ≥5 years and Adolescents: IV: 15 mg/kg as a single dose; maximum dose: 750 mg/dose. Dosing based on a single study comparing intravenous ferric carboxymaltose with oral ferrous sulfate (n=30; 15 patients received ferric carboxymaltose); the ferric carboxymaltose group experienced more improvement and fewer adverse effects than the oral ferrous sulfate group (DelRosso 2021).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling. Based on experience in adults, no adjustments are likely needed in nondialysis-dependent patients with chronic kidney disease.
There are no dosage adjustments provided in the manufacturer's labeling.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Injectafer: 750 mg/15 mL (15 mL)
Solution, Intravenous [preservative free]:
Injectafer: 100 mg/2 mL (2 mL)
No
Each mL of Injectafer contains 50 mg of elemental iron
IV: Administer as slow IV push (undiluted) at a rate of ~100 mg/minute (doses ≤750 mg) or over 15 minutes (1 g dose). May also administer as an IV infusion (diluted) over at least 15 minutes.
Avoid extravasation (may cause persistent discoloration at the extravasation site). Monitor; if extravasation occurs, discontinue administration at that site.
Parenteral: IV: In prospective and retrospective pediatric studies, doses were infused over 15 to 30 minutes (Carman 2019; Powers 2017; Sasankan 2021). Administer diluted solution over ≥15 minutes (manufacturer's labeling); maximum infusion time of 60 minutes has been reported (Laass 2014). For doses of 750 mg, may administer undiluted as a slow IV push at a rate of ~100 mg/minute; for doses of 1,000 mg, administer over 15 minutes. Avoid extravasation (may cause persistent discoloration at the extravasation site). If extravasation occurs, discontinue administration at that site.
Iron-deficiency anemia: Treatment of iron-deficiency anemia (IDA) in adults and pediatric patients ≥1 year of age with intolerance to oral iron or unsatisfactory response to oral iron; treatment of IDA in adults with nondialysis-dependent chronic kidney disease (ND-CKD).
Abdominal surgery, major (perioperative anemia management); Chemotherapy-associated anemia; Iron-deficiency anemia in inflammatory bowel disease; Iron deficiency in heart failure with reduced ejection fraction; Restless legs syndrome
Ferric carboxymaltose may be confused with ferric gluconate, ferumoxytol
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults, unless otherwise noted.
>10%: Endocrine & metabolic: Hypophosphatemia (children, adolescents: 13%; adults: 1% to 27%)
1% to 10%:
Cardiovascular: Flushing (children, adolescents, adults: ≤4%), hypertension (1% to 4%), hypotension (≤1%)
Dermatologic: Erythema of skin (≤3%), skin discoloration at injection site (≤1%), skin rash (children, adolescents: 8%; adults: 1%)
Gastrointestinal: Dysgeusia (1%), gastrointestinal infection (children, adolescents: 3%), nausea (1% to 7%), vomiting (children, adolescents, adults: ≤5%)
Hematologic & oncologic: Decreased platelet count (children, adolescents: 3%), decreased white blood cell count (children, adolescents: 3%)
Hepatic: Increased liver enzymes (children, adolescents, adults: 1% to 3%)
Local: Injection site reaction (children, adolescents, adults: 3% to 8%)
Nervous system: Dizziness (1% to 2%), headache (children, adolescents: 5%; adults: 1%)
Respiratory: Nasopharyngitis (children, adolescents: 3%)
<1%:
Endocrine & metabolic: Increased gamma-glutamyl transferase
Gastrointestinal: Abdominal pain, constipation, diarrhea
Hypersensitivity: Anaphylaxis, nonimmune anaphylaxis
Nervous system: Paresthesia
Respiratory: Sneezing
Postmarketing:
Cardiovascular: Chest discomfort, fetal bradycardia, syncope, tachycardia
Dermatologic: Pruritus, urticaria
Hypersensitivity: Angioedema, hypersensitivity reaction
Nervous system: Chills
Neuromuscular & skeletal: Arthralgia, back pain, osteomalacia (hypophosphatemic)
Respiratory: Dyspnea
Miscellaneous: Fever
Hypersensitivity to ferric carboxymaltose or any component of the formulation
Concerns related to adverse effects:
• Hypersensitivity: Serious hypersensitivity reactions, including anaphylactic-type reactions (some life-threatening and fatal) have been reported. Monitor during and for at least 30 minutes after administration and until clinically stable. Signs/symptoms of serious hypersensitivity reaction include shock, hypotension, loss of consciousness, and/or collapse. Equipment for resuscitation, medication, and trained personnel experienced in handling emergencies should be immediately available during infusion.
• Hypertension: Transient elevations in systolic blood pressure (sometimes with facial flushing, dizziness, or nausea) were observed in studies; usually occurred immediately after dosing and resolved within 30 minutes. Monitor blood pressure following infusion.
• Hypophosphatemia: Symptomatic hypophosphatemia has been reported. Most cases occurred after repeated exposure in patients without a history of renal impairment and resolved within 3 months. Risk factors may include a history of GI disorders associated with malabsorption of fat-soluble vitamins or phosphate, use (current or prior) of medications that affect proximal renal tubular function, hyperparathyroidism, vitamin D deficiency, and malnutrition. Monitor serum phosphate levels in patients at risk for hypophosphatemia who require a repeat course of treatment.
Other warnings/precautions:
• Laboratory alterations: Lab assays may overestimate serum iron and transferrin bound irons for ~24 hours after infusion.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Dimercaprol: May enhance the nephrotoxic effect of Iron Preparations. Risk X: Avoid combination
Ferric carboxymaltose was not found to cross the placenta in an in vitro placental perfusion study (Malek 2010). Iron transfer to the fetus is regulated by the placenta (BSH [Pavord 2020]; NAS 2020).
There is a risk of adverse maternal reactions (eg, anaphylaxis, hypotension, shock) following use of parenteral iron which may result in fetal bradycardia, especially during the second and third trimesters. Although the risk is rare, immediate treatment for anaphylactoid and/or hypersensitivity reactions should be available (BSH [Pavord 2020]).
Maternal iron requirements increase during pregnancy. Untreated iron deficiency and iron-deficiency anemia (IDA) in pregnant patients are associated with adverse pregnancy outcomes, including low birth weight, preterm birth, and increased perinatal mortality (ACOG 2021; BSH [Pavord 2020]). Maternal iron deficiency is also associated with fatigue, increased risk of postpartum depression, and possibly postpartum hemorrhage (BSH [Pavord 2020]).
Oral and parenteral iron are effective at replacing iron stores in pregnant patients (ACOG 2021). Most studies note iron therapy improves maternal hematologic parameters; however, data related to clinical outcomes in the mother and neonate are limited (FIGO 2019; NAS 2020; USPSTF [Siu 2015]). Parenteral iron therapy may be used in pregnant patients who cannot tolerate or respond to oral iron, when iron deficiency occurs later in pregnancy, or when malabsorption is present (ACOG 2021; BSH [Pavord 2020]).
Ferric carboxymaltose has been evaluated for the treatment of IDA during pregnancy (Breymann 2017; Froessler 2018; Khalafallah 2018; Oskovi-Kaplan 2021; Qassim 2018; Rogozińska 2021; Shim 2018; Shin 2021; Wani 2019). Based on available data, adverse developmental outcomes have not been reported following maternal use of ferric carboxymaltose in pregnancy. However, due to limited safety data in early pregnancy, use of intravenous iron is generally not started until the second or third trimester (ACOG 2021; BSH [Pavord 2020]; FIGO 2019).
IV iron may be considered for the treatment of restless legs syndrome in pregnant patients with serum ferritin <30 ng/mL who have failed oral iron; use of IV iron should be avoided during the first trimester (Picchietti 2015; Schneider 2015).
Iron is present in breast milk.
Endogenous iron concentrations in breast milk vary by postpartum age and are lower than concentrations in the maternal plasma (Dorea 2000; Emmett 1997). Breast milk concentrations of iron are maintained in lactating patients with mild to moderate iron-deficiency anemia (IDA), but concentrations decrease if IDA is moderate to severe (El-Farrash 2012) or severe (Kumar 2008).
Iron concentrations in breast milk increase following maternal administration of ferric carboxymaltose; highest concentrations were observed 24 hours following administration to 11 postpartum patients with IDA (Breymann 2008).
Ferric carboxymaltose has been evaluated in multiple studies for the treatment of postpartum IDA (Sultan 2019; Vanobberghen 2021). Adverse events in breastfed infants were limited and similar to those observed following maternal use of an oral iron preparation (Breymann 2008). In a study of 57 patients with moderate to severe anemia, a single postpartum dose of ferric carboxymaltose was found to treat anemia and replenish iron reserves for up to 6 months (Kaur 2021).
Iron deficiency and IDA are associated with adverse effects in postpartum patients (eg, altered cognition, depression, fatigue) that may influence interactions with the infant. Iron supplementation in the postpartum patient should be initiated as soon as possible following delivery when gestational anemia is a concern (WHO 2016). Parenteral iron therapy may be used in postpartum patients with uncorrected anemia at delivery who cannot tolerate, do not respond to, or are noncompliant with oral iron therapy, or the severity of anemia requires prompt management (BSH [Pavord 2020]).
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.
Hemoglobin and hematocrit, serum ferritin, transferrin saturation, serum phosphate (in patients at risk for hypophosphatemia who require a repeat course of treatment); vital signs (including blood pressure); monitor for signs/symptoms of hypersensitivity (monitor for ≥30 minutes following the end of administration and until clinically stable); monitor infusion site for extravasation.
Chronic kidney disease: Monitor transferrin saturation and ferritin more frequently following a course of IV iron (KDIGO 2013).
Chemotherapy-associated anemia (off-label use): Iron, total iron-binding capacity, transferrin saturation, or ferritin levels at baseline and periodically (Rizzo 2010).
Iron deficient patients should have serum ferritin assessed 2 to 4 weeks after infusion course is completed; if serum ferritin >50 to 100 ng/mL is not achieved, then another iron dose should be administered (DeLoughery 2017).
CKD patients should have sufficient iron to achieve and maintain hemoglobin of 11 to 12 g/dL; to achieve and maintain this target hemoglobin for patients with nondialysis dependent CKD, sufficient iron should be administered to maintain a transferrin saturation (TSAT) of 20%, and a serum ferritin level ≥100 ng/mL (KDIGO 2013).
Ferric carboxymaltose is a colloidal iron (III) hydroxide in complex with carboxymaltose, a carbohydrate polymer that releases iron necessary to the function of hemoglobin, myoglobin, and specific enzyme systems; allows transport of oxygen via hemoglobin. Ferric carboxymaltose is a non-dextran formulation that allows for iron uptake (into reticuloendothelial system) without the release of free iron (Szczech 2010).
Distribution: Vd: ~3 L.
Half-life elimination:
Children and Adolescents: ~9.7 hours.
Adults: 7 to 12 hours.
Time to peak:
Children and Adolescents: Median: 7 minutes.
Adults: 0.25 to 1.21 hours following administration.
Excretion: Urine (negligible).
Solution (Injectafer Intravenous)
100 mg/2 mL (per mL): $102.62
750 mg/15 mL (per mL): $102.62
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