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Ferric Carboxymaltose

Medically reviewed on September 10, 2018

Pronunciation

(FER ik kar box ee MAWL tose)

Index Terms

  • Ferinject
  • Iron Carboxymaltose
  • Iron Dextri-Maltose
  • VIT 45

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Injectafer: 750 mg/15 mL (15 mL)

Brand Names: U.S.

  • Injectafer

Pharmacologic Category

  • Iron Salt

Pharmacology

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

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)

Off Label Uses

Abdominal surgery, major (perioperative anemia management)

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 anemia

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 disease

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 fraction

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 syndrome

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

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.

Dosing: Renal Impairment

Chronic kidney disease, nondialysis dependent: No dosage adjustment necessary (indicated for use in nondialysis CKD)

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer’s labeling.

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 Salts. 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 Considerations

Ferric carboxymaltose has been evaluated for the treatment of iron deficiency anemia (IDA) during pregnancy (Aporta Rodriguez 2016; Breymann 2017; Froessler 2014; Pels 2015) and postpartum (Breymann 2008).

Untreated IDA is associated with adverse pregnancy outcomes including low birth weight, preterm delivery, and maternal postpartum anemia.

Iron requirements increase during pregnancy. All females should be screened for iron deficiency during pregnancy; if IDA is present, supplemental iron (in addition to prenatal vitamins) should be administered. 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).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience injection site pain. Have patient report immediately to prescriber shortness of breath, severe dizziness, passing out, flushing, muscle pain, muscle weakness, injection site irritation, severe nausea, severe vomiting, or severe headache (HCAHPS).

• Educate patient about signs of a significant reaction (eg, 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. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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