Ferric carboxymaltose (Injectafer) is a novel iron formulation that allows higher doses of the drug to be infused at relatively less time. Compared to iron sucrose (Venofer) that can be infused at a maximum rate of 100 mg per 15 minutes, Ferric carboxymaltose (Injectafer) allows a dose of up to 1000 mg per15 - 20 minutes.

Ferric carboxymaltose (Injectafer) Uses:

• Iron deficiency anemia:

  • Use for the 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 non-dialysis-dependent chronic kidney disease (ND-CKD)

• Off-Label Use of Ferric carboxymaltose in Adults:

  • Used for the abdominal surgery, major (perioperative anemia management)
  • Used for the chemotherapy-associated anemia
  • Used for the iron deficiency anemia in inflammatory bowel disease
  • Used for the iron deficiency in heart failure with a reduced ejection fraction
  • Used for the restless legs syndrome

Ferric carboxymaltose (Injectafer) Dose in Adults

 Note: Dose expressed as elemental iron.

Ferric carboxymaltose (Injectafer) Dose for perioperative management of anemia in patients undergoing major abdominal surgery:

• 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).

Ferric carboxymaltose (Injectafer) Dose in the treatment of Chemotherapy-associated anemia (off-label):

• IV: Median total ferric carboxymaltose dose: 1,000 mg (range: 600 to 1,500 mg);
• Consider dividing larger doses to a maximum single dose of 750 mg and separated by 7 days.

Ferric carboxymaltose (Injectafer) Dose in the treatment of Iron deficiency anemia: IV:

• <50 kg:

  • 15 mg/kg on day 1;
  • repeat dose after at least one weak
  • Maximum: 750 mg/single dose; 1,500 mg per course.
  • May repeat the course of therapy if anemia reoccurs.

• ≥50 kg:

  • 750 mg on day 1;
  • repeat dose after at least one weak
  • maximum: 750 mg/single dose; 1,500 mg per course.
  • May repeat the course of therapy if anemia reoccurs.

Ferric carboxymaltose (Injectafer) Dose in the treatment of Iron deficiency anemia in inflammatory bowel disease (off-label):

• IV: 500 or 1,000 mg/dose on day 1 (and if needed based on hemoglobin values, days 8 and 15);
• Patients less than 67 kg received a maximum of 500 mg per infusion.

Ferric carboxymaltose (Injectafer) Dose in the treatment of Iron deficiency in heart failure with reduced ejection fraction (off-label):

• Note:
  • Patients may or may not be anemic.
  • Iron deficiency in clinical trials was defined as a serum ferritin level of less than 100 mcg/L or a serum ferritin level of 100 to 300 mcg/L if transferrin saturation is less than 20 percent.
• IV: 200 mg once in a weak (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) 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;

Ferric carboxymaltose (Injectafer) Dose in the treatment of Restless legs syndrome (off-label):

• IV: 500 mg on the first day;
• repeat after 5 days.

Ferric carboxymaltose (Injectafer) Dose in Childrens

Ferric carboxymaltose (Injectafer) Dose in Children:

The efficacy and safety of the drug have not been fully established. In clinical trials, a dose of 15 mg/kg (maximum total dose of 1000 mg) was administered over 15 - 20 minutes and found to be safe and effective.

Ferric carboxymaltose (Injectafer) Pregnancy Risk Category: B3

• In vitro placental perfusion studies did not show that ferric carboxymaltose crossed the placenta.
• Anemia (Iron Deficiency Anemia) and iron deficiency (IDA), if left untreated in a pregnant woman, can lead to adverse events such as low birth weight, preterm births, or higher perinatal mortality.
• The treatment of iron deficiency (or IDA) in pregnancy is generally the same as for non-pregnant women.
• Most studies confirm that iron therapy has a positive effect on maternal hematologic parameters. However, there is not much information about the clinical outcomes for mother and baby.
• During pregnancy, maternal iron requirements rise.
• Affective iron levels can be maintained for the foetus regardless of maternal iron status.
• According to available data, there have been no adverse developmental outcomes reported in relation to maternal use of ferric caroxymaltose during pregnancy.
• Because of limited safety data, intravenous iron should not be started in the first or third trimester.
• Although oral preparations are usually sufficient, parenteral iron therapy can be used for those who are unable to tolerate or won't take oral iron. This is also true in severe iron deficiency cases or malabsorption.
• For the treatment of IDA in pregnancy, ferric carboxymaltose was evaluated.

Use of ferric carboxymaltose during breastfeeding

• Breast milk contains iron.
• Iron levels in breast milk are maintained for women with mild to moderate iron deficiency (IDA). However, concentrations may drop if IDA becomes severe.
• Breastfed infants experienced fewer adverse events than those who were given an oral iron supplement.
• According to the manufacturer breastfeeding during therapy is a decision that should be made after considering the risks to infants and the benefits to mothers.
• After the infusion, breast milk had the highest iron content after 24 hours.
• Multiple studies have evaluated the carboxymaltose drug formulation in the treatment of postpartum IDA.
• Infants should be checked for GI toxicity (such as constipation and diarrhea).

Dose in Kidney Disease:

Chronic kidney disease, non-dialysis dependent:

• No dosage adjustment necessary (indicated for use in non-dialysis CKD)

Dose in Liver disease:

The manufacturer’s labeling doesn't provide any dosage adjustments.

Common Side Effects of Ferric carboxymaltose (Injectafer):

• Endocrine & metabolic:

  • Decreased serum phosphate

Less Common Side Effects of Ferric carboxymaltose (Injectafer):

• Cardiovascular:

  • Increased Blood Pressure
  • Hypotension
  • Flushing
  • Hypertension

• Central Nervous System:

  • Dizziness
  • Headache

• Dermatologic:

  • Skin Discoloration At Injection Site

• Endocrine & Metabolic:

  • Hypophosphatemia

• Gastrointestinal:

  • Nausea
  • Dysgeusia
  • Vomiting
  • Constipation

• Hepatic:

  • Increased Serum ALT

Contraindications to Ferric carboxymaltose (Injectafer):

Hypersensitivity to ferric carboxymaltose and any component of the formulation

Warnings and precautions

• Hypersensitivity

  • Monitor for at least 30 seconds after administration, and continue monitoring until you feel stable.
  • Shock, hypotension, loss consciousness, and/or collapsing are all signs/symptoms of severe hypersensitivity reactions.
  • There have been reports of severe hypersensitivity reactions including anaphylactic-type reactions that can be fatal and life-threatening.
  • During infusion, equipment for resuscitation and medication should be readily available.

• Hypertension:

  • After infusion, monitor blood pressure.
  • Studies showed that transient elevations of systolic pressure, sometimes with dizziness, facial flushing or nausea, were common.
  • These usually occurred within 30 minutes after the dosing.

Ferric carboxymaltose: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

• Hemoglobin and hematocrit, serum ferritin, iron saturation;
• vital signs (including blood pressure);
• monitor for signs/symptoms of hypersensitivity (monitor for 30 minutes and more than 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.

Chemotherapy-associated anemia (off-label use):

• Iron, total iron-binding capacity, transferrin saturation, or ferritin levels at baseline and periodically.

Iron deficient patients should have serum ferritin assessed 2 to 4 weeks after the infusion course is completed; if serum ferritin more than 50 to 100 ng/mL is not achieved, then another iron dose should be administered.

How to administer Ferric carboxymaltose (Injectafer)?

IV:

• Administer as a 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. 

Mechanism of action of Ferric carboxymaltose (Injectafer):

• Ferric carboxymaltose (III) colloidal iron hydroxide is in combination with carboxymaltose.
• This carbohydrate polymer releases iron that is necessary for the function of hemoglobin and myoglobin.
• It allows oxygen transport via hemoglobin. Ferric carboxymaltose, a non-dextran formula that allows iron uptake (into reticuloendothelial systems) without the release free iron.

Half-life elimination:

• 7 to 12 hours

Time to peak:

• 0.25 to 1.2 hours following administration

Excretion:

• Urine (negligible)

International Brands of Ferric carboxymaltose:

• Injectafer
• Ferinject
• Ferium

Ferric carboxymaltose Brand Names in Pakistan: