INJECTAFER® (ferric carboxymaltose injection)

INJECTAFER® (ferric carboxymaltose injection)

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INJECTAFER® (ferric carboxymaltose injection)

Ferric carboxymaltose, an iron replacement product, is an iron carbohydrate complex with the chemical name of polynuclear iron (III) hydroxide 4(R)-(poly-(1→4)-O-α-Dglucopyranosyl)-oxy-2(R),3(S),5(R),6-tetrahydroxy-hexanoate. It has a relative molecular weight of approximately 150,000 Da corresponding to the following empirical formula: [FeOx(OH)y(H2O)z]n [{(C6H10O5)m (C6H12O7)}l]k, where n ≈ 103 , m ≈ 8, l≈ 11, and k ≈ 4 (l represents the mean branching degree of the ligand).

Indications and usage

Injectafer is an iron replacement product indicated for the treatment of iron deficiency anemia (IDA) in adult patients:

  • who have intolerance to oral iron or have had unsatisfactory response to oral iron, or
  • who have non-dialysis dependent chronic kidney disease.

Mechanism of Action

Ferric carboxymaltose is a colloidal iron (III) hydroxide in complex with carboxymaltose, a carbohydrate polymer that releases iron.

Pharmacokinetics

After administration of a single dose of Injectafer of 100 to 1,000 mg of iron in iron deficient patients, maximum iron concentration of 37 µg/mL to 333 µg/mL were obtained respectively after 15 minutes to 1.21 hours post dose. The volume of distribution was estimated to be 3 L.

The iron injected or infused was rapidly cleared from the plasma, the terminal half-life ranged from 7 to 12 hours. Renal elimination of iron was negligible.

Dosage and administration

For patients weighing 50 kg or more, the recommended dosage is Injectafer 750 mg intravenously in two doses separated by at least 7 days for a total cumulative dose of 1,500 mg of iron per course. Alternatively, for patients weighing 50 kg or more, Injectafer 15 mg/kg to a maximum of 1,000 mg may be administered as a single-dose treatment course.

For patients weighing less than 50 kg, the recommended dosage is Injectafer 15 mg/kg body weight intravenously in two doses separated by at least 7 days per course.

Injectafer treatment may be repeated if iron deficiency anemia reoccurs.

Contraindications

Hypersensitivity to Injectafer or any of its inactive components.

Warnings and precautions

  • Hypersensitivity Reactions: Observe for signs and symptoms of hypersensitivity during and after Injectafer administration for at least 30 minutes and until clinically stable following completion of each administration.
  • Symptomatic Hypophosphatemia: Monitor serum phosphate levels in patients at risk for low serum phosphate who require a repeat course of treatment.
  • Hypertension: Monitor patients closely for signs and symptoms of hypertension following each Injectafer administration

Adverse reactions

The most common adverse reactions (>2%) are nausea, hypertension, flushing, injection site reactions, erythema, hypophosphatemia, and dizziness.

Preparation and Administration Administer Injectafer intravenously, either as an undiluted slow intravenous push or by infusion. When administered via infusion, dilute up to 1,000 mg of iron in no more than 250 mL of sterile 0.9% sodium chloride injection, USP, such that the concentration of the infusion is not less than 2 mg of iron per mL and administer over at least 15 minutes.

When added to an infusion bag containing 0.9% sodium chloride injection, USP, at concentrations ranging from 2 mg to 4 mg of iron per mL, Injectafer solution is physically and chemically stable for 72 hours when stored at room temperature. To maintain stability, do not dilute to concentrations less than 2 mg iron/mL.

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Inspect parenteral drug products visually for the absence of particulate matter and discoloration prior to administration. The product contains no preservatives. Each vial of Injectafer is intended for single-dose only.

When administering Injectafer 750 mg as a slow intravenous push, give at the rate of approximately 100 mg (2 mL) per minute. For Injectafer 1000 mg, administer as a slow intravenous push over 15 minutes. Avoid extravasation of Injectafer since brown discoloration of the extravasation site may be long lasting. Monitor for extravasation. If extravasation occurs, discontinue the Injectafer administration at that site.

Discard unused portion.

Side effects

  • Cardiac disorders: Tachycardia
  • General disorders and administration site conditions: Chest discomfort, chills, pyrexia
  • Metabolism and nutrition disorders: Hypophosphatemia
  • Musculoskeletal and connective tissue disorders: Arthralgia, back pain, hypophosphatemic osteomalacia (rarely reported event)
  • Nervous system disorders: Syncope
  • Respiratory, thoracic and mediastinal disorders: Dyspnea
  • Skin and subcutaneous tissue disorders: Angioedema, erythema, pruritus, urticaria
  • Pregnancy: Fetal bradycardia
Use in specific populations

Pregnancy: Parenteral iron administration may be associated with hypersensitivity reactions, which may have serious consequences, such as fetal bradycardia. Advise pregnant women of the potential risk to a fetus.

There are risks to the mother and fetus associated with untreated IDA in pregnancy as well as risks to the fetus associated with maternal severe hypersensitivity reactions

Untreated IDA in pregnancy is associated with adverse maternal outcomes such as postpartum anemia. Adverse pregnancy outcomes associated with IDA include increased risk for preterm delivery and low birth weight.

Severe adverse reactions including circulatory failure (severe hypotension, shock including in the context of anaphylactic reaction) may occur in pregnant women with parenteral iron products (such as Injectafer) which may cause fetal bradycardia, especially during the second and third trimester.

Lactation: The available published data on the use of ferric carboxymaltose in lactating women demonstrate that iron is present in breast milk. Among the breastfed infants, adverse reactions included constipation and diarrhea but none of the adverse reactions reported were considered related to ferric carboxymaltose exposure through breastmilk. There is no information on the effects of ferric carboxymaltose on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Injectafer in addition to any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition.

Pediatric Use: Safety and effectiveness have not been established in pediatric patients.

Overdosage

Excessive dosages of Injectafer may lead to accumulation of iron in storage sites potentially leading to hemosiderosis. A patient who received Injectafer 18,000 mg over 6 months developed hemosiderosis with multiple joint disorder, walking disability, and asthenia. Hypophosphatemic osteomalacia was reported in a patient who received Injectafer 4,000 mg over 4 months. Partial recovery followed discontinuation of Injectafer.

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). [See the USP controlled room temperature.] Do not freeze.

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