Injectafer

Recommended Dosage

Recommended Dosage for Treatment of Iron Deficiency Anemia

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.
• In adult patients, Injectafer 15 mg/kg body weight up to a maximum of 1,000 mg intravenously may be administered as a single-dose per 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.

Recommended Dosage in Patients with Iron Deficiency with Heart Failure

See Table 1 for recommended dosage for treatment of iron deficiency in patients with heart failure and New York Heart Association class II/III to improve exercise capacity.

Table 1: Recommended Dosage in Patients with Iron Deficiency with Heart Failure

Administer a maintenance dose of 500 mg at 12, 24 and 36 weeks if serum ferritin <100 ng/mL or serum ferritin 100-300 ng/mL with transferrin saturation <20%. There are no data available to guide dosing beyond 36 weeks or with Hb ≥15 g/dL.

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 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.

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 a single dose.

When administering Injectafer 500 or 750 mg as a slow intravenous push, give at the rate of approximately 100 mg (2 mL) per minute.  For Injectafer 1,000 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.

  Repeat Treatment Monitoring Safety Assessment

Injectafer treatment may be repeated if IDA or iron deficiency in heart failure reoccurs.  Check serum phosphate levels in patients at risk for low serum phosphate who require a repeat course of treatment or for any patient who receives a repeat course of treatment within three months [see Warnings and Precautions ].  Treat hypophosphatemia as medically indicated.

Pregnancy

Risk Summary

Parenteral iron administration may be associated with hypersensitivity reactions [see Warnings and Precautions ], which may have serious consequences, such as fetal bradycardia (see Clinical Considerations). Advise pregnant women of the potential risk to a fetus.  Published studies and available data from postmarketing reports with intravenous Injectafer are insufficient to assess the risk of major birth defects and miscarriage.  

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 (see Clinical Considerations).

In animal reproduction studies, administration of ferric carboxymaltose to rabbits during the period of organogenesis caused adverse developmental outcomes including fetal malformations and increased implantation loss at maternally toxic doses of approximately 12% to 23% of the human weekly dose of 750 mg (based on body surface area).   

The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.  In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Clinical Considerations
Disease-associated maternal and/or embryo/fetal risk

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

Fetal/Neonatal adverse reactions

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.

Data
Human Data

Published data from randomized controlled studies, prospective observational studies and retrospective studies on the use of ferric carboxymaltose in pregnant women have not reported an association with intravenous ferric carboxymaltose and major birth defects and miscarriage.  However, these studies cannot establish or exclude the absence of any drug-related risk during pregnancy.   

Animal Data

Administration of ferric carboxymaltose to rats as a one-hour intravenous infusion up to 30 mg/kg/day iron on gestation days 6 to 17 did not result in adverse embryonic or fetal findings.  This daily dose in rats is approximately 40% of the human weekly dose of 750 mg based on body surface area.  In rabbits, ferric carboxymaltose was administered as a one-hour infusion on gestation days 6 to 19 at iron doses of 4.5, 9, 13.5, and 18 mg/kg/day.  Malformations were seen starting at the daily dose of 9 mg/kg (23% of the human weekly dose of 750 mg).  Spontaneous abortions occurred starting at the daily iron dose of 4.5 mg/kg (12% of the human weekly dose of 750 mg based on body surface area).  Pre-implantation loss was at the highest dose.  Adverse embryonic or fetal effects were observed in the presence of maternal toxicity.

A pre- and post-natal development study was conducted in rats at intravenous doses up to 18 mg/kg/day of iron (approximately 23% of the weekly human dose of 750 mg based on body surface area).  There were no adverse effects on survival of offspring, their behavior, sexual maturation or reproductive parameters.

Lactation

Risk Summary

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

The safety and effectiveness of Injectafer for IDA in pediatric patients aged 1 year and older who have normal kidney function and have either intolerance to oral iron or have had unsatisfactory response to oral iron have been established. Use of Injectafer for this indication in this age group is supported by evidence from adequate and well-controlled studies of Injectafer in adults with additional pharmacodynamic and safety data in pediatric patients aged 1 year and older [see Adverse Reactions and Clinical Pharmacology ].

Safety and effectiveness of Injectafer have not been established in pediatric patients less than 1 year of age with IDA.

Safety and effectiveness of Injectafer have not been established to improve exercise capacity in pediatric patients with ID and symptomatic heart failure.

Geriatric Use

Of the 1,775 subjects in clinical studies of Injectafer, 50% were 65 years and over, while 25% were 75 years and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Hypersensitivity Reactions

Serious hypersensitivity reactions, including anaphylactic-type reactions, some of which have been life-threatening and fatal, have been reported in patients receiving Injectafer. Patients may present with shock, clinically significant hypotension, loss of consciousness, and/or collapse. Monitor patients for signs and symptoms of hypersensitivity during and after Injectafer administration for at least 30 minutes and until clinically stable following completion of the infusion. Only administer Injectafer when personnel and therapies are immediately available for the treatment of serious hypersensitivity reactions [see Adverse Reactions ].  Treat hypophosphatemia as medically indicated.

Hypertension

In clinical studies, hypertension was reported in 4% (67/1,775) of subjects in clinical trials 1 and 2. Transient elevations in systolic blood pressure, sometimes occurring with facial flushing, dizziness, or nausea were observed in 6% (106/1,775) of subjects in these two clinical trials. These elevations generally occurred immediately after dosing and resolved within 30 minutes.   Monitor patients for signs and symptoms of hypertension following each Injectafer administration [see Dosage and Administration ].

Laboratory Test Alterations

In the 24 hours following administration of Injectafer, laboratory assays may overestimate serum iron and transferrin bound iron by also measuring the iron in Injectafer.