Ferric Carboxymaltose - Mechanism of Action, Indications, Dosage, and Adverse Drug Reactions

Overview

An iron replacement medication called Ferric carboxymaltose injection is used to treat iron deficiency anemia (IDA), characterized by low red blood cell count due to low iron content in adults and children one year and older. It is advantageous for those with heart failure (HF) who wish to increase their capacity for exercise, those who have an intolerance to oral iron supplements, those who have had an inadequate reaction to oral iron, and those who suffer from non-dialysis-dependent chronic kidney disease (CKD), a long-standing kidney disease. It is infused intravenously over 15 minutes. On July 25, 2013, the Food and Drug Administration (FDA) approved a treatment course of 1500 mg (milligrams), to be taken in two doses of no more than 750 mg each, spaced by seven days.

Drug Group

Ferric carboxymaltose belongs to a drug class of iron replacement products. It treats iron deficiency anemia in adults and children who have not responded well to oral supplements or are intolerant to oral iron. Moreover, it can enhance exercise capacity in adult patients with NYHA (New York Heart Association) class II or III heart failure. It is recommended for those with non-dialysis-dependent chronic renal disease. This iron-carbohydrate complex offers an effective option for restoring iron deficiency and enhancing general health.

Indications

Adult patients with the following conditions should use Ferric carboxymaltose to address their iron deficiency anemia (IDA):

• Chronic kidney disease that is not reliant on dialysis (which helps to remove extra fluid and waste materials from the blood when the kidneys are unable to perform their function).

• Intolerance to oral iron or have not responded satisfactorily to it.

Contraindications

Patients who have previously experienced hypersensitivity (allergic reaction) to Ferric carboxymaltose or any of its constituents are not advised to use Ferric carboxymaltose injections.

Dosage Forms and Available Strengths

Ferric carboxymaltose injection is available in two forms: 750 mg (milligrams) per 15 mL (milliliters) and a 1,000 mg/20 mL single-dose vial, with a dose of 50 mg/mL (milligrams per milliliter).

Warnings and Precautions

• Hypersensitivity Reactions: Serious hypersensitivity reactions, including potentially deadly ones, can occur in patients receiving a Ferric carboxymaltose injection. Shock (insufficient blood flow to the body tissues), hypotension (low blood pressure), loss of consciousness, and collapse are possible reactions to this. Until they are clinically stable, patients should be observed for at least 30 minutes in cases of hypersensitivity.

• Symptomatic Hypophosphatemia: Patients at risk of low serum phosphate following repeated injections of Ferric carboxymaltose have been known to experience hypophosphatemia (low phosphate levels in the blood), necessitating therapeutic intervention. Gastrointestinal issues, drugs that impact renal function, hyperparathyroidism (an overactive parathyroid gland secretes a high amount of parathyroid hormones), a lack of vitamin D, and malnourishment are risk factors. The majority of cases are resolved in three months. For patients who are at risk of having low serum phosphate, repeat treatment and monitor their levels.

• Hypertension: After taking a Ferric carboxymaltose injection, patients should be watched for symptoms related to hypertension (high blood pressure), such as flushing of the face, lightheadedness, or nausea.

• Laboratory test alterations: Within 24 hours of administering Ferric carboxymaltose injection, laboratory assays have the potential to overestimate transferrin-bound iron and serum iron.

For Patients

What Is Iron Deficiency Anemia?

Iron deficiency anemia is a disorder in which the body does not have enough iron, which causes the red blood cells necessary for the body to store and carry oxygen to decrease. The lack of hemoglobin, which is necessary for red color and oxygen transport, is the cause of this. The deficiency can cause modest symptoms that deteriorate over time, such as fatigue, weakness, pale complexion, headaches, chest pain, dizziness, lightheadedness, cold hands and feet, tongue inflammation, brittle nails, and poor appetite, particularly in newborns and young children.

How Does Ferric Carboxymaltose Work?

An intravenous iron replacement product called Ferric carboxymaltose treats iron deficiency anemia. Restocking its iron reserves helps the body make more red blood cells. This medicine falls under the category of iron replacements and serves as a first line of treatment.

What Are the Clinical Uses of Ferric Carboxymaltose?

• Iron Deficiency Anemia: Patients over one-year-old who cannot tolerate oral iron therapy or who do not receive the desired results from oral iron supplements are treated for iron deficiency anemia with Ferric carboxymaltose, an iron replacement medication. Adult patients with chronic renal disease who are not dependent on dialysis can also use it.

• Heart Failure: Ferric carboxymaltose can increase the ability to exercise in adult patients with NYHA (New York Heart Association) class II or III heart failure.

• Mechanism of Action: Intravenous (IV) administration of Ferric carboxymaltose releases iron through a complex between colloidal iron (III) hydroxide and carboxymaltose, a carbohydrate polymer. When taken, it helps the body produce healthy red blood cells and raises iron levels.

• Red Cell absorption: Using positron emission tomography (PET), red cell iron absorption from Ferric carboxymaltose in patients with iron deficiency ranges from 91 to 99 percent.

How Is Ferric Carboxymaltose Administered?

It is advised that patients who weigh 110 pounds or more use Ferric carboxymaltose 750 mg intravenously in two doses spaced at least seven days apart for a cumulative total of 1,500 mg of iron per course. As an alternative, Ferric carboxymaltose 15 mg/kg (milligrams per kilogram) up to 1,000 mg may be given as a single dose of medication for individuals weighing 110 pounds or more. The suggested intravenous dosage for individuals under 110 pounds is Ferric carboxymaltose 15 mg/kg (milligrams per kilogram). Body weight is divided into two doses for at least seven days per course. If iron deficiency anemia reappears, Ferric carboxymaltose therapy may be repeated.

What Are the Side Effects of Ferric Carboxymaltose?

The most frequent side effects (greater than two percent) are erythema (redness), hypophosphatemia (low phosphate levels in the blood), flushing, injection site reactions, nausea, and dizziness.

What Are the Things to Inform the Doctor Before Taking Ferric Carboxymaltose?

• If patients are allergic to Ferric carboxymaltose, they should avoid using it.

• Inform the doctor if the patient has ever experienced elevated blood pressure or an allergic response to an intravenous iron injection.

• Inform the doctor if patients are or want to become pregnant. Ferric carboxymaltose may trigger significant reactions in the mother that could alter the baby's heartbeat, while it is unknown if this will harm the unborn child.

• Iron deficiency anemia during pregnancy may raise the possibility of low birth weight or early delivery. Ferric carboxymaltose treatment for this illness may have advantages over hazards for the infant.

• Inform the doctor if the patient observes constipation or diarrhea in the nursing child if the patient is breastfeeding.

Dietary Considerations

Maintain the same eating habits unless otherwise advised by healthcare practitioners.

Missed Dose

If patients miss the Ferric carboxymaltose injection appointment, give the physician an appointment for instructions.

Overdose

If a Ferric carboxymaltose overdose occurs, get immediate medical assistance or contact the poison helpline.

Pain, coughing, wheezing, shortness of breath, coughing up blood, weight loss, or decreased growth in a child are some of the symptoms of a Ferric carboxymaltose overdose.

Storage and Handling

Store between 20°C (degrees Celsius) and 25°C (68°F (degrees Fahrenheit) and 77°F); the maximum temperatures allowed are 15°C and 30°C (59°F and 86°F). Avoid freezing.

For Doctors

What Are the Pharmacological Actions of Ferric Carboxymaltose?

Pharmacodynamics

Positron emission tomography (PET) analysis revealed that the red cell absorption of Ferric carboxymaltose's 59-Fe and 52-Fe varied from 61 to 99 percent. The range of red cell uptake in patients with iron insufficiency was 91 to 99 percent. The red cell uptake in patients with renal anemia varied from 61 to 84 percent.

Mechanism of Action

Colloidal iron (III) hydroxide and carboxymaltose, a polymer of carbohydrates that releases iron, are combined to form ferric carboxymaltose.

Pharmacokinetics

• Absorption: The maximum serum concentration in patients with iron deficiency was 37 μg/mL (micrograms per milliliter) to 333 μg/mL when they received a single dosage of 100 to 1000 mg of iron. These values were measured between 15 minutes and 1.21 hours after the dosage.

• Distribution: Following a single Ferric carboxymaltose dosage, the estimated distribution volume was 101 ounces.

• Excretion: Iron was essentially eliminated by the kidneys. Ferric carboxymaltose has a terminal half-life of 7 to 12 hours. For pediatric patients, the elimination half-life was roughly 9.7 hours.

What Are the Drug Interactions of Ferric Carboxymaltose?

The drugs that interact with Ferric carboxymaltose include:

• Benazepril.

• Captopril.

• Carbonyl iron.

• Chloramphenicol.

• Dimercaprol.

• Enalapril.

• Enalaprilat.

• Erdafitinib.

• Ferric maltol.

• Ferrous fumarate.

• Ferrous gluconate.

• Ferrous sulfate.

• Fosinopril.

• Gallium citrate Ga-67.

• Heme iron polypeptide.

• Iron bisglycinate.

• Iron polysaccharide.

• Iron protein succinylate.

• Lisinopril.

• Moexipril.

• Multivitamin with iron.

• Multivitamins with iron and fluoride.

• Multivitamin, prenatal.

• Oxidronate.

• Perindopril.

• Quinapril.

• Ramipril.

• Trandolapril.

• Vitamin E.

Clinical Studies

Two randomized, open-label, controlled clinical trials were conducted to assess the safety and effectiveness of Ferric carboxymaltose in treating iron deficiency anemia (IDA). Ferric carboxymaltose was given twice at a dose of 15 mg/kg body weight, with a minimum of seven days between each administration, to achieve the maximum single dose of 750 mg of iron. This resulted in a cumulative dose of 1,500 mg of iron.

Trial 1: Iron Deficiency Anemia in Patients Who Are Intolerant to Oral Iron or Have Had Unsatisfactory Response to Oral Iron

Patients with IDA who did not respond well to oral iron or were intolerant to it throughout the 14-day oral iron run-in period were included in the trial. For the remaining 14 days, Cohort 1 patients were randomized to either a Ferric carboxymaltose injection or oral iron. 90 percent of cohort 2 individuals received iron sucrose after being randomly assigned to get Ferric carboxymaltose or another IV iron as per standard of care. The study patients ranged in age from 18 to 94 years old, with a mean age of 43.

Of these, 94 percent were female; the race distribution was 42 percent Caucasian, 32 percent African American, 24 percent Hispanic, and two percent other. Heavy uterine hemorrhage (47 percent) and gastrointestinal issues (17 percent) were the main causes of IDA. Patients receiving Ferric carboxymaltose demonstrated increases in mean ferritin and transferrin saturation at Day 35 compared to baseline.

Trial 2: Iron Deficiency Anemia in Patients with Non-Dialysis-Dependent Chronic Kidney Disease

Ferric carboxymaltose's effectiveness and safety were assessed in this study in patients with reduced renal function and iron deficiency anemia. Patients with non-dialysis-dependent chronic renal disease and those with ferritin levels below 100 ng/mL or below 300 ng/mL in the case of transferrin saturation below 30 percent, were included in the study. Patients in the study were randomized to receive an iron sucrose injection or Ferric carboxymaltose. Patients in the study ranged in age from 19 to 101, with a mean of 67 years. Of these, 64 percent were female, and the majority (54 percent) were Caucasian, 26 percent African American, 18 percent Hispanic, and two percent were of other ethnicities. According to the study, before Day 56, individuals receiving Ferric carboxymaltose had higher mean ferritin levels and transferrin saturation.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Studies on carcinogenicity have not been conducted using Ferric carboxymaltose. In vitro microbial mutagenesis (Ames) assay, in vitro chromosome aberration test in human lymphocytes, in vitro mammalian cell mutation assay in mouse lymphoma L5178Y/TK+/- cells, and in vivo mouse micronucleus test at single intravenous doses up to 500 mg/kg were the genetic toxicology studies that did not find Ferric carboxymaltose to be genotoxic. Male and female rats received intravenous Ferric carboxymaltose at iron concentrations of up to 30 mg/kg over an hour in a study combining male and female fertility. The animals received doses thrice weekly on Days 0, 3, and 7. Early embryonic development, fertility, or the ability to mate were unaffected. The dose of 30 mg/kg administered to animals, based on body surface area, is roughly 40 percent of the 750 mg dose administered to humans.

Specific Considerations

• Pregnancy: Ferric carboxymaltose is widely considered safe during pregnancy and can treat iron deficiency anemia in expectant mothers; nevertheless, careful patient monitoring and assessment are necessary.

• Breastfeeding: It is important to monitor gastrointestinal toxicity in breastfed infants whose mothers are getting Ferric carboxymaltose during lactation. The mother's ability to metabolize iron can have a beneficial effect on the iron status of the child.

• Pediatric Use: Children and adolescents one year old and older may utilize Ferric carboxymaltose. It efficiently restores iron reserves and treats anemia in children with iron deficiency.

• Geriatric Use: Ferric carboxymaltose is still a useful treatment for iron deficiency anemia in the elderly. Personalized dosage and monitoring, taking age-related variables into account, are required.