Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Injectafer: 750 mg/15 mL (15 mL)
Pharmacology
Mechanism of Action
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).
Pharmacokinetics/Pharmacodynamics
Distribution
Vd: ~3 L
Excretion
Urine (negligible)
Time to Peak
0.25 to 1.2 hours following administration
Half-Life Elimination
7 to 12 hours
Use: Labeled Indications
Iron deficiency anemia: Treatment of iron deficiency anemia (IDA) in adults with intolerance to oral iron or unsatisfactory response to oral iron; treatment of IDA in adults with nondialysis-dependent chronic kidney disease (ND-CKD)
Use: Off Label
Abdominal surgery, major (perioperative anemia management)b
Data from a randomized, controlled trial comparing ferric carboxymaltose therapy to usual perioperative care (eg, no treatment, continued observation, oral iron recommendations, and allogeneic blood transfusion) in patients with iron deficiency anemia scheduled for abdominal surgery supports the use of ferric carboxymaltose in perioperative patients. Results showed a reduced need for blood transfusion in the perioperative period, a shorter hospital stay, enhanced restoration of iron stores, and higher mean hemoglobin concentration 4 weeks after surgery in those receiving intravenous iron Froessler 2016.
Chemotherapy-associated anemiac
Data from a prospective observational study in adult patients with active malignancy and absolute or functional iron deficiency suggests ferric carboxymaltose (with or without concomitant erythropoiesis-stimulating agents [ESAs]) may be utilized to correct anemia Steinmetz 2013.
Iron deficiency anemia in inflammatory bowel diseaseb
Data from a multicenter, randomized, controlled, open-label trial supports the use of ferric carboxymaltose in patients with inflammatory bowel disease (IBD) and iron deficiency anemia (Evstatiev 2011). Clinical experience also supports the use of ferric carboxymaltose in this patient population. Intravenous iron therapy is indicated when IBD is active, anemia is moderate to severe, the patient is intolerant to oral iron, erythropoietin agents are being used, or a rapid response (ie, planned surgery) is needed Aksan 2017, Gomollón 2013.
Iron deficiency in heart failure with reduced ejection fractionbyes
Data from two randomized, double-blind, placebo-controlled trials (Fair-HF and CONFIRM-HF) in patients with New York Heart Association (NYHA) functional class II or III heart failure with reduced ejection fraction and iron deficiency (with or without anemia) support the use of ferric carboxymaltose for improvement in symptoms, functional capacity, and quality of life Anker 2009, Ponikowski 2015.
The European Society for Cardiology guidelines for the diagnosis and treatment of acute and chronic heart failure and the ACC/AHA/HFSA guidelines for the management of heart failure suggest that ferric carboxymaltose may be considered in symptomatic patients with heart failure associated with reduced ejection fraction (HFrEF) and iron deficiency to improve symptoms as well as exercise capacity and quality of life ACC/AHA/HFSA [Yancy 2017], ESC [Ponikowski 2016].
Restless legs syndromeyes
The American Academy of Neurology guidelines for the treatment of restless legs syndrome (RLS) recommend the use of ferric carboxymaltose, regardless of ferritin level, for the improvement of RLS symptoms in patients with moderate to severe RLS.
Contraindications
Hypersensitivity to ferric carboxymaltose or any component of the formulation
Dosage and Administration
Dosing: Adult
Note: Dose expressed as elemental iron.
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: Median total ferric carboxymaltose dose: 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: IV:
<50 kg: 15 mg/kg on day 1; repeat dose after at least 7 days (maximum: 750 mg/single dose; 1,500 mg per course). May repeat course of therapy if anemia reoccurs.
≥50 kg: 750 mg on day 1; repeat dose after at least 7 days (maximum: 750 mg/single dose; 1,500 mg per course). May repeat course of therapy if anemia reoccurs.
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).
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).
Restless legs syndrome (off-label use): IV: 500 mg on day 1; repeat after 5 days (AAN [Winkelman 2016])
Dosing: Geriatric
Refer to adult dosing.
Reconstitution
May administer undiluted (for IV push) or diluted (for infusion). When administering as an IV infusion, dilute up to 750 mg in a maximum of 250 mL of 0.9% sodium chloride to a concentration of 2 to 4 mg/mL; concentration should be ≥2 mg/mL. Discard unused portion of vial (single-use).
Administration
IV: Administer as slow IV push (undiluted) at a rate of ~100 mg/minute or 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.
Storage
Store intact vials at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F); do not freeze. Solutions diluted in 0.9% sodium chloride at concentrations of 2-4 mg/mL are stable for 72 hours at room temperature.
Drug Interactions
Dimercaprol: May enhance the nephrotoxic effect of Iron Preparations. Avoid combination
Test Interactions
Serum or transferrin bound iron levels may be falsely elevated if assessed within 24 hours of ferric carboxymaltose administration.
Adverse Reactions
>10%: Endocrine & metabolic: Decreased serum phosphate (27%; <2 mg/dL [0.65 mmol/L]; transient)
1% to 10%:
Cardiovascular: Increased blood pressure (6%; transient, systolic), flushing (4%), hypertension (4%), hypotension
Central nervous system: Dizziness (2%), headache (1%)
Dermatologic: Skin discoloration at injection site (1%)
Endocrine & metabolic: Hypophosphatemia (2%)
Gastrointestinal: Nausea (7%), vomiting (2%), constipation (1%), dysgeusia (1%)
Hepatic: Increased serum ALT (1%)
<1%, postmarketing, and/or case reports: Abdominal pain, anaphylaxis, angioedema, arthralgia, back pain, chest discomfort, chills, diarrhea, dyspnea, erythema, fever, hypersensitivity, increased gamma-glutamyl transferase, irritation at injection site, pain at injection site, paresthesia, pruritus, skin rash, sneezing, syncope, tachycardia, urticaria
Warnings/Precautions
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.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Other warnings/precautions:
- Laboratory alterations: Lab assays may overestimate serum iron and transferrin bound irons for ~24 hours after infusion.
Monitoring Parameters
Hemoglobin and hematocrit, serum ferritin, iron saturation; 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).
Pregnancy
Pregnancy Considerations
Ferric carboxymaltose was not found to cross the placenta in an in vitro placental perfusion study (Malek 2010).
Maternal iron requirements increase during pregnancy. Adequate iron concentrations to the fetus can be maintained regardless of maternal iron status, except in severe cases of anemia (IOM 2001). Untreated iron deficiency and iron deficiency anemia (IDA) in a pregnant female may be associated with adverse events, including low birth weight, preterm birth, or increased perinatal mortality (ACOG 95 2008; IOM 2001; Pavord 2012).
In general, treatment of iron deficiency or IDA in pregnancy is the same as in non-pregnant females. The majority of studies note iron therapy improves maternal hematologic parameters, however, information related to clinical outcomes in the mother and neonate is limited (Qassim 2018; Siu 2015). Oral preparations are generally sufficient, however parenteral iron therapy may be used in females who cannot tolerate or will not take oral iron, in cases of severe iron deficiency, or when malabsorption is present (ACOG 95 2008; Pavord 2012).
Ferric carboxymaltose has been evaluated for the treatment of IDA during pregnancy (Aporta Rodriguez 2016; Breymann 2017b; Froessler 2018; Qassim 2018; Shim 2018). 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 (Breymann 2017a; Pavord 2012).
Patient Education
What is this drug used for?
- It is used to treat anemia.
Frequently reported side effects of this drug
- Nausea
- Flushing
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Low phosphate like vision changes, confusion, mood changes, muscle pain, muscle weakness, shortness of breath, difficulty breathing, or difficulty swallowing.
- Dizziness
- Passing out
- Vision changes
- Injection site skin discoloration
- Severe headache
- Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
