Ferric Carboxymaltose (Monograph)

Brand name: Injectafer
Drug class: Iron Preparations
Chemical name: Iron Dextri-Maltose
Molecular formula: FeIII_w([C₆H₁₀O₅]_aC₆H₁₁O₇)_x(OH)_yO_z•nH₂O
CAS number: 9007-72-1

Introduction

Polynuclear iron (III)-hydroxide carbohydrate complex; stable non-dextran iron formulation used to replenish and maintain the total body content of iron.

Uses for Ferric Carboxymaltose

Iron Deficiency Anemia Not Amenable to Oral Iron Therapy

Treatment of iron deficiency anemia in adults who are intolerant of or have had an unsatisfactory response to oral iron preparations.

Iron Deficiency Anemia in Patients with Non-Dialysis-Dependent Chronic Kidney Disease

Treatment of iron deficiency anemia in adults with non-dialysis-dependent chronic kidney disease.

Ferric Carboxymaltose Dosage and Administration

Administration

IV Administration

Administer by slow IV injection or IV infusion only.

Avoid extravasation; may cause potentially long-lasting brown discoloration of extravasation site. Monitor for extravasation during administration; if extravasation occurs, discontinue administration at affected site.

Monitor for hypersensitivity reactions during and for ≥30 minutes after administration until clinically stable. Administer only when appropriate agents and personnel for the treatment of serious hypersensitivity reactions are readily available.

Dilution

IV infusion: Dilute up to 750 mg in ≤250 mL of 0.9% sodium chloride injection, providing a concentration of ≥2 mg of iron per mL.

Discard any unused portion of the diluted or undiluted ferric carboxymaltose solution.

Rate of Administration

Slow IV injection: Administer undiluted at a rate of approximately 100 mg/minute.

IV infusion: Administer diluted solution over ≥15 minutes.

Dosage

Dosage expressed in terms of mg of elemental iron. Ferric carboxymaltose injection contains the equivalent of 50 mg of elemental iron per mL.

Adults

Iron Deficiency Anemia Not Amenable to Oral Iron Therapy

IV

Patients ≥50 kg: 2 doses of 750 mg separated by at least 7 days, for a total cumulative dosage of 1.5 g of iron per treatment course.

Patients <50 kg: 2 doses of 15 mg/kg (not exceeding 750 mg per dose) separated by at least 7 days, for a total cumulative dosage not exceeding 1.5 g of iron per treatment course.

May repeat treatment if iron deficiency anemia reoccurs.

Iron Deficiency Anemia in Patients with Non-Dialysis-Dependent Chronic Kidney Disease

IV

Patients ≥50 kg: 2 doses of 750 mg separated by at least 7 days, for a total cumulative dosage of 1.5 g of iron per treatment course.

Patients <50 kg: 2 doses of 15 mg/kg (not exceeding 750 mg per dose) separated by at least 7 days, for a total cumulative dosage not exceeding 1.5 g of iron per treatment course.

May repeat treatment if iron deficiency anemia reoccurs.

Prescribing Limits

Adults

IV

Maximum single dose: 750 mg.

Maximum cumulative dosage per treatment course: 1.5 g.

Special Populations

No special populations dosage recommendations at this time.

Cautions for Ferric Carboxymaltose

Contraindications

Known hypersensitivity to ferric carboxymaltose or any ingredient in the formulation.

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions, including serious or life-threatening and fatal anaphylactic-type reactions, reported. Serious hypersensitivity reactions, which may present as shock, clinically important hypotension, loss of consciousness, and/or collapse, reported in 0.1% of patients receiving ferric carboxymaltose in clinical trials; other serious or severe potential hypersensitivity reactions (e.g., pruritus, rash, urticaria, wheezing, hypotension) reported in 1.5% of such patients.

Hypertension

Hypertension was reported in 3.8% of patients receiving ferric carboxymaltose in clinical trials. Transient elevations in systolic BP, sometimes accompanied by facial flushing, dizziness, or nausea, reported in 6% of patients; usually observed immediately after administration of the drug and resolved within 30 minutes.

Monitor patients for signs and symptoms of hypertension following each dose of ferric carboxymaltose.

Specific Populations

Pregnancy

Category C.

Lactation

In lactating women with postpartum iron deficiency anemia, mean breast milk iron concentrations were higher in women receiving IV ferric carboxymaltose than in those receiving oral ferrous sulfate. Use caution in nursing women.

Pediatric Use

Safety and efficacy not established.

Geriatric Use

No substantial differences in safety or efficacy relative to younger adults, but increased sensitivity cannot be ruled out.

Common Adverse Effects

Nausea, hypertension, flushing/hot flush, hypophosphatemia, dizziness, vomiting, injection site discoloration, headache, increased serum ALT, dysgeusia, hypotension.

Drug Interactions

Formal drug interaction studies not performed to date.

Specific Laboratory Tests

Laboratory Test	Interaction
Serum iron and transferrin-bound iron concentrations	Potential for falsely elevated serum iron and transferrin-bound iron concentrations when assessed within 24 hours of ferric carboxymaltose administration

Ferric Carboxymaltose Pharmacokinetics

Absorption

Bioavailability

Rapid, dose-dependent increase in total serum iron concentrations observed following single IV doses of 0.1–1 g.

Peak iron concentrations of 37–333 mcg/mL observed 0.25–1.21 hours following IV injection or infusion of a single dose of 0.1–1 g in patients with iron deficiency.

Distribution

Extent

Iron administered as ferric carboxymaltose rapidly distributed to bone marrow, liver, and spleen; estimated distribution volume 3 L.

RBC iron uptake of 61–99% following administration of radiolabeled ferric carboxymaltose.

RBC iron uptake of 91–99% reported 24 days following administration of radiolabeled ferric carboxymaltose in patients with iron deficiency.

Special Populations

RBC iron uptake of 61–84% reported 24 days following administration of radiolabeled ferric carboxymaltose in patients with renal anemia.

Elimination

Elimination Route

Negligible renal elimination.

Half-life

7–12 hours.

Stability

Storage

Parenteral

Injection

20–25°C (may be exposed to 15–30°C); do not freeze.

Ferric carboxymaltose solutions containing 2–4 mg/mL of iron in 0.9% sodium chloride injection are stable for 72 hours at room temperature.

Compatibility

Parenteral

Solution Compatibility1

Compatible
Sodium chloride 0.9%

Actions

Polynuclear iron (III)-hydroxide carbohydrate complex with a molecular weight of approximately 150,000.
Stable, non-dextran iron formulation that permits uptake of iron by the reticuloendothelial system without the release of free iron.

Advice to Patients

Risk of hypersensitivity reactions. Importance of informing clinician if any signs or symptoms of hypersensitivity reactions (e.g., rash, pruritus, dizziness, lightheadedness, dyspnea, wheezing, swelling) occur.
Importance of informing clinician of prior hypersensitivity or unusual reactions to parenteral iron preparations.
Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary and herbal supplements (e.g., oral iron supplements), as well as any concomitant illnesses (e.g., liver disease may increase likelihood of iron overload).
Importance of women informing clinician if they are or plan to become pregnant or plan to breast-feed.
Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.