Ferrlecit

Ferrlecit is indicated for the treatment of iron deficiency anemia in adult patients and in pediatric patients age 6 years and older with chronic kidney disease receiving hemodialysis who are receiving supplemental epoetin therapy.

• Adult Patients - The recommended adult dosage is 10 mL (125 mg of elemental iron) diluted in 100 mL of 0.9% sodium chloride administered by intravenous infusion over 1 hour per dialysis session or undiluted as a slow intravenous injection (at a rate of up to 12.5 mg/min) per dialysis session. (
  2.2 Adult Dosage and Administration

  The recommended dosage of Ferrlecit for the repletion treatment of iron deficiency in hemodialysis patients is 10 mL of Ferrlecit (125 mg of elemental iron). Ferrlecit may be diluted in 100 mL of 0.9% sodium chloride administered by intravenous infusion over 1 hour per dialysis session. Ferrlecit may also be administered undiluted as a slow intravenous injection (at a rate of up to 12.5 mg/min) per dialysis session. For repletion treatment most patients may require a cumulative dose of 1000 mg of elemental iron administered over 8 dialysis sessions. Ferrlecit has been administered at sequential dialysis sessions by infusion or by slow intravenous injection during the dialysis session itself.

  Data from Ferrlecit postmarketing spontaneous reports indicate that individual doses exceeding 125 mg may be associated with a higher incidence and/or severity of adverse events

  [see Adverse Reactions (6.2)]

  .
  )
• Pediatric Patients - The recommended pediatric dosage is 0.12 mL/kg (1.5 mg/kg of elemental iron) diluted in 25 mL 0.9% sodium chloride and administered by intravenous infusion over 1 hour per dialysis session. (
  2.3 Pediatric Dosage and Administration

  The recommended pediatric dosage of Ferrlecit for the repletion treatment of iron deficiency in hemodialysis patients is 0.12 mL/kg Ferrlecit (1.5 mg/kg of elemental iron) diluted in 25 mL 0.9% sodium chloride and administered by intravenous infusion over 1 hour per dialysis session. The maximum dosage should not exceed 125 mg per dose.
  )
• Do not mix Ferrlecit with other medications or add to parenteral nutrition solutions for intravenous infusion.
• Administer in 0.9% saline. (
  2 DOSAGE AND ADMINISTRATION

  • Adult Patients - The recommended adult dosage is 10 mL (125 mg of elemental iron) diluted in 100 mL of 0.9% sodium chloride administered by intravenous infusion over 1 hour per dialysis session or undiluted as a slow intravenous injection (at a rate of up to 12.5 mg/min) per dialysis session.
  • Pediatric Patients - The recommended pediatric dosage is 0.12 mL/kg (1.5 mg/kg of elemental iron) diluted in 25 mL 0.9% sodium chloride and administered by intravenous infusion over 1 hour per dialysis session.
  • Do not mix Ferrlecit with other medications or add to parenteral nutrition solutions for intravenous infusion.
  • Administer in 0.9% saline.

  2.1 Important Administration Instructions

  The dosage of Ferrlecit is expressed in terms of mg of elemental iron. Each 5 mL sterile, single-dose vial contains 62.5 mg of elemental iron (12.5 mg/mL).

  Do not mix Ferrlecit with other medications or add to parenteral nutrition solutions for intravenous infusion. The compatibility of Ferrlecit with intravenous infusion vehicles other than 0.9% sodium chloride has not been evaluated. Parenteral drug products should be inspected visually for particulate matter and discoloration before administration, whenever the solution and container permit. If diluted, use immediately.

  Ferrlecit treatment may be repeated if iron deficiency reoccurs.

  2.2 Adult Dosage and Administration

  The recommended dosage of Ferrlecit for the repletion treatment of iron deficiency in hemodialysis patients is 10 mL of Ferrlecit (125 mg of elemental iron). Ferrlecit may be diluted in 100 mL of 0.9% sodium chloride administered by intravenous infusion over 1 hour per dialysis session. Ferrlecit may also be administered undiluted as a slow intravenous injection (at a rate of up to 12.5 mg/min) per dialysis session. For repletion treatment most patients may require a cumulative dose of 1000 mg of elemental iron administered over 8 dialysis sessions. Ferrlecit has been administered at sequential dialysis sessions by infusion or by slow intravenous injection during the dialysis session itself.

  Data from Ferrlecit postmarketing spontaneous reports indicate that individual doses exceeding 125 mg may be associated with a higher incidence and/or severity of adverse events

  [see Adverse Reactions (6.2)]

  .

  2.3 Pediatric Dosage and Administration

  The recommended pediatric dosage of Ferrlecit for the repletion treatment of iron deficiency in hemodialysis patients is 0.12 mL/kg Ferrlecit (1.5 mg/kg of elemental iron) diluted in 25 mL 0.9% sodium chloride and administered by intravenous infusion over 1 hour per dialysis session. The maximum dosage should not exceed 125 mg per dose.
  )

Injection: 62.5 mg/5 mL (12.5 mg/mL) clear, dark brown liquid in single-dose vial

• Pregnancy: Risk of hypersensitivity reaction which may have serious consequences for the fetus. Use only if clearly needed (contains benzyl alcohol). (
  8.1 Pregnancy

  Risk Summary

  Parenteral iron administration may be associated with hypersensitivity reactions

  [see Warnings and Precautions (5.1)]

  , which may have serious consequences, such as fetal bradycardia

  (see Clinical Considerations)

  . Advise pregnant women of the potential risk to the fetus. Available data from postmarketing reports with Ferrlecit use in pregnancy are insufficient to assess the risk of major birth defects and miscarriage.

  Ferrlecit contains benzyl alcohol as a preservative. Because benzyl alcohol is rapidly metabolized by a pregnant woman, benzyl alcohol exposure in the fetus is unlikely. However, adverse reactions have occurred in premature neonates and low-birth-weight infants who received intravenously administered benzyl alcohol–containing drugs

  [see Warnings and Precautions (5.4)and Use in Specific Populations (8.4)]

  . Consider alternative iron replacement therapies without benzyl alcohol.

  There are risks to the mother and fetus associated with untreated iron deficiency anemia in pregnancy

  (see Clinical Considerations)

  .

  In the absence of maternal toxicity, Ferrlecit was not teratogenic to offspring of pregnant mice or rats at clinically relevant exposures

  (see Data)

  .

  The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defects, 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%–4% and 15%–20%, respectively.

  Clinical Considerations

  Disease-associated maternal and/or embryo/fetal risk

  Untreated iron deficiency anemia (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.

  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 intravenous iron administration, which may have serious consequences on the fetus such as fetal bradycardia, especially during the second and third trimesters.

  Data

  Animal data

  Ferrlecit was administered intravenously to pregnant mice during gestation days 6 to 15 at doses of 5, 30, and 100 mg Fe/kg/day to assess embryofetal development. No teratogenic effects were seen in offspring at the highest dose, representing maternal exposure of approximately 4 times maximum human exposure based on body surface area. There were increased fetal resorptions and decreased fetal weights at doses that caused maternal toxicity as evidenced by decreased body-weight gain and decreased food consumption.

  Ferrlecit was administered intravenously to pregnant rats during gestation days 6 to 15 at doses of 4 and 20 mg Fe/kg/day to assess embryofetal development. No teratogenic effects were seen in offspring at the highest dose, representing maternal exposure of approximately 1.5 times maximum human exposure based on body surface area. There were decreases in gestation index and litter size, increased fetal resorptions, and decreased fetal weights at doses that caused maternal toxicity as evidenced by decreased body-weight gain and decreased food consumption.
  )
• Lactation: Not recommended when breastfeeding. (
  8.2 Lactation

  Risk Summary

  Ferrlecit contains benzyl alcohol. Because benzyl alcohol is rapidly metabolized by a lactating woman, benzyl alcohol exposure in the breastfed infant is unlikely. However, adverse reactions have occurred in premature neonates and low-birth-weight infants who received intravenously administered benzyl alcohol–containing drugs

  [see Warnings and Precautions (5.4)and Use in Specific Populations (8.4)]

  . Consider alternative iron replacement therapies without benzyl alcohol for use during lactation.

  There are no available data on the presence of Ferrlecit in human or animal milk, the effects on milk production, or the effects on the breastfed child.
  )
• Pediatric Use: Safety and effectiveness have not been established in pediatric patients <6 years of age. (
  8.4 Pediatric Use

  The safety and effectiveness of Ferrlecit have been established in pediatric patients 6 to 15 years of age

  [see Dosage and Administration (2.3), Clinical Pharmacology (12.3), and Clinical Studies (14)]

  . Safety and effectiveness in pediatric patients younger than 6 years of age have not been established.

  Benzyl Alcohol Toxicity and Pediatrics

  Ferrlecit is not approved for use in neonates or infants. Serious adverse reactions including fatal reactions and the "gasping syndrome" occurred in premature neonates and low-birth-weight infants in the neonatal intensive care unit who received drugs containing benzyl alcohol as a preservative. In these cases, benzyl alcohol dosages of 99 to 234 mg/kg/day produced high levels of benzyl alcohol and its metabolites in the blood and urine (blood levels of benzyl alcohol were 0.61 to 1.378 mmol/L). Additional adverse reactions included gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse. Benzyl alcohol contained in Ferrlecit may cause serious and anaphylactoid reactions in infants and children up to 3 years old. The administration of medications containing benzyl alcohol to newborns or premature neonates has been associated with a fatal "gasping syndrome" (symptoms include a striking onset of gasping syndrome, hypotension, bradycardia, and cardiovascular collapse). Preterm, low-birth-weight infants may be more likely to develop these reactions because they could be less able to metabolize benzyl alcohol. The minimum amount of benzyl alcohol at which serious adverse reactions may occur is not known (Ferrlecit contains 9 mg of benzyl alcohol per mL)

  [see Warnings and Precautions (5.4)]

  .
  )

• Hypersensitivity Reactions: Monitor patients for signs and symptoms of hypersensitivity during and after Ferrlecit administration for at least 30 minutes and until clinically stable following completion of the infusion. Only administer Ferrlecit when personnel and therapies are immediately available for the treatment of anaphylaxis and other hypersensitivity reactions. (
  5.1 Hypersensitivity Reactions

  Serious hypersensitivity reactions, including anaphylactic-type reactions, some of which have been life-threatening and fatal, have been reported in patients receiving Ferrlecit in postmarketing experience. Patients may present with shock, clinically significant hypotension, loss of consciousness, or collapse. Monitor patients for signs and symptoms of hypersensitivity during and after Ferrlecit administration for at least 30 minutes and until clinically stable following completion of the infusion. Only administer Ferrlecit when personnel and therapies are immediately available for the treatment of anaphylaxis and other hypersensitivity reactions

  [see Adverse Reactions (6)]

  .

  In the single-dose, postmarketing safety study one patient experienced a life-threatening hypersensitivity reaction (diaphoresis, nausea, vomiting, severe lower back pain, dyspnea, and wheezing for 20 minutes) following Ferrlecit administration. Among 1,097 patients who received Ferrlecit in this study, there were 9 patients (0.8%) who had an adverse reaction that, in the view of the investigator, precluded further Ferrlecit administration. These included one life-threatening reaction, six allergic reactions (including pruritus, facial flushing, chills, dyspnea/chest pain, and rash), and two other reactions (hypotension and nausea). Another 2 patients experienced (0.2%) allergic reactions not deemed to represent drug intolerance (nausea/malaise and nausea/dizziness) following Ferrlecit administration.
  )
• Hypotension: Ferrlecit may cause hypotension. Monitor patients for signs and symptoms of hypotension during and following each Ferrlecit dose. (
  5.2 Hypotension

  Ferrlecit may cause clinically significant hypotension. Hypotension associated with lightheadedness, malaise, fatigue, weakness or severe pain in the chest, back, flanks, or groin has been reported. These hypotensive reactions may or may not be associated with signs and symptoms of hypersensitivity reactions and usually resolve within one to two hours. In the single-dose safety study, postadministration hypotensive events were observed in 22/1,097 patients (2%) following Ferrlecit administration. Transient hypotension may occur during dialysis. Administration of Ferrlecit may augment hypotension caused by dialysis. Monitor patients for signs and symptoms of hypotension during and following Ferrlecit administration

  [see Adverse Reactions (6.1)].
  )
• Iron Overload: Regularly monitor hematologic responses during Ferrlecit therapy. Do not administer Ferrlecit to patients with iron overload. (
  5.3 Iron Overload

  Excessive therapy with parenteral iron can lead to excess storage of iron with the possibility of iatrogenic hemosiderosis. Patients receiving Ferrlecit require periodic monitoring of hematologic and iron parameters (hemoglobin, hematocrit, serum ferritin, and transferrin saturation).
  )
• Benzyl Alcohol Toxicity: Premature and low-birth-weight infants may be more likely to develop toxicity. (
  5.4 Risk of Serious Adverse Reactions in Infants Due to Benzyl Alcohol Preservative

  Ferrlecit is not approved for use in neonates or infants. Serious and fatal adverse reactions including "gasping syndrome" can occur in neonates and low-birth-weight infants treated with benzyl alcohol–preserved drugs, including Ferrlecit. The "gasping syndrome" is characterized by central nervous system depression, metabolic acidosis, and gasping respirations. The minimum amount of benzyl alcohol at which serious adverse reactions may occur is not known (Ferrlecit contains 9 mg of benzyl alcohol per mL)

  [see Use in Specific Populations (8.4)]

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  )