Evolution of injectable iron – Iron dextran to Ferric Derisomaltose

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What is Injectable Iron?

Iron deficiency anemia, which is a condition caused due to a lower number of red blood cells which are responsible for carrying oxygen to the blood, is treated by Iron supplements in general. However, some of the patients can’t register these supplements prescribed for oral use. Either the iron supplements fail to work, or the patients are allergic to the supplements. In this condition, a solution is injected into the muscles of the buttock or intravenously to treat iron deficiency anemia in the form of an iron replacement product which is known as iron dextran injection. The iron stores in the body are replenished and the reaction starts within 24 to 48 hours and may last up to 3 to 4 days after taking the injection. This injectable form of iron works better and faster with more efficiency.

What is Iron Dextran?

Patients with iron deficiency who cannot take oral iron supplements are treated with iron dextran, which is available in the form of injections. Used for intramuscular or intravenous use, iron dextran is a dark brown, slightly viscous liquid complex of dextran and ferric hydroxide. The special cases in which oral administration of iron supplements is impossible or unsatisfactory, iron dextran is used for treatment.

Iron dextran is also used for the treatment of iron deficiency by replenishing iron stores of the body in Peritoneal Dialysis Dependent (PDD-CKD) and Hemodialysis Dependant (HDD-CKD) – Chronic Kidney Disease patients receiving erythropoietin or in Non-Dialysis Dependant-Chronic Kidney Disease (NDD-CKD) patients receiving or not receiving erythropoietin. The cells of the reticuloendothelial system are used to remove the circulating iron dextran from the plasma after the injection of iron dextran. The reticuloendothelial cells split the complex into its components of dextran and iron.

For the formation of transferrin or to a higher extent to form the physiological forms of iron, hemosiderin, or ferritin, the iron is immediately bound to the available protein moieties. The depleted iron stores and hemoglobin gets replenished by the iron that is infused which is subject to physiological control. 72 hours is needed for the major portion of intramuscular injection of iron dextran to be absorbed. The remaining iron is absorbed within a period of 3 to 4 weeks. The protein binding of iron dextran is considered to be 100% after the release from dextran. The poly glucose dextran is either excreted or metabolized.

However, there can be several side effects from the use of iron dextran. Dizziness, shivering, tingling sensation on feet or hands, and flushing may be some of the side effects. A pharmacist or a doctor should be consulted if any of these effects last or worsen. Vomiting, nausea, headache, moderate to high fever, chills, and ache in the muscle, joints, and back are some of the side effects that can arise after 4 to 7 days of taking the injection. If the medication is injected into a muscle, the side effects take longer than 3 to 4 days to be visible. But if it is injected in a vein, then the side effects are visual in less than 3 to 4 days.

What is Ferric Derisomaltose?

A complex of derisomaltose and iron (III) which is used for treating iron deficiency or anemia caused by deficiency of iron is in the form of ferric derisomaltose. The iron is released in a reaction of derisomaltose, which is an iron carbohydrate oligosaccharide. Ferric derisomaltose is list likely to cause serious hypersensitivity which is at high risk in case of the usage of other iron supplements or injections and also non-inferior to iron sucrose, which is another form of iron that is often administered in the cases of deficiency of iron.

The patients who have an insufficient clinical response to orally administered iron or the ones who have experienced intolerance to oral iron preparations are prescribed ferric derisomaltose as the medicinal drug. Patients with non-hemodialysis-dependent chronic kidney diseases are recommended this treatment by using ferric derisomaltose. In critical cases where there is a requirement for rapid delivery of iron, ferric derisomaltose is indicated in countries such as the United Kingdom and Australia.

Hemoglobin content is boosted in the blood flow and the reticulocyte count is increased for the treatment of anemia caused by Iron deficiency and the other symptoms, of ferric derisomaltose. Falsely reduced serum calcium and serum bilirubin levels might be falsely elevated when parental iron, such as ferric derisomaltose is incorporated. Iron is released by the iron carbohydrate oligosaccharide present in the derisomaltose and Iron (III) hydroxide components of ferric derisomaltose. For incorporation into the hemoglobin molecule, the released iron binds to the transferrin, which is the transport protein taken to the erythroid precursor cells to do so.

Evolution – Iron Dextran to Ferric Derisomaltose

When the patient has issues with oral iron dosage i.e. intolerance or poor effectiveness of oral iron supplements, then intravenous (IV) iron is the therapy of choice for treating iron deficiency. In case of severe HSR or low rates of iron content in the body, ferric derisomaltose rapidly repleats iron parameters. In 1932 the first parental iron formulation known as the ferric oxyhydroxide was introduced but abandoned quite soon because of the negative impact on the medical community in terms of the perception of toxicity.

With the approval of intravenous and intramuscular injections, an effective injection known as iron dextran was introduced which was considered to be effective and safe. However, due to the misinformation about the cause and misinterpretation of infusion a reaction which was repeatedly complained about, iron dextran remained a minor product. Following this period the use of iron dextran was supplanted with the introduction of novel parenteral iron formulations.

The HMW formulation of iron dextran was found to be the reason for the reported overwhelming preponderance of SAEs when 30 million doses of administered IV iron were examined in 2004. The estimated SAE frequency of the other formulations was comparatively safe below 1:250,000 administrations. The availability of Dexferrum was eradicated and removed from the markets. Eventually, the interest in iron dextran vanished from the market despite the excellent safety records of low molecular weight iron dextran as it was removed from the treatment paradigm in most dialysis centers.

IS became the dominant iron formulation after the administration of a collective dose of parenteral iron in one or two visits became effectively discarded as a priority, for outpatients with iron deficiency due to chronic conditions related to iron lack, bariatric surgery, chemotherapy-induced anemia, cancer, pregnancy, heavy uterine bleeding, and inflammatory bowel disease.

In 2007 ferric carboxymaltose was approved in Europe and by the FDA in 2013 for administration with a couple of infusions of 750 mg each, i.e. a complete dose of 1500 mg.

Ferric Carboxymaltose was used to deliver a controlled amount of iron to the target tissues by using a novel iron complex which consists of a ferric hydroxide core which is stabilised by a carbohydrate shell. It was made available in the market by the name of Ferinject(R). It was recorded that ferric carboxymaltose took less than or equal to 15 minutes to administer a dose of up to 1000 mg of iron to replenish the iron stores of the human body.

However the levels of hyperphosphatemia was found to be lower in iron isomaltoside when compared to ferric carboxymaltose. Thus, iron isomaltoside 1000 was introduced in the market which replaced ferric carboxymaltose.

Following the interaction with the FDA, Pharmacosmos’ new formulation initially known as iron isomaltoside 1000, was renamed ferric derisomaltose. In 2009, ferric derisomaltose was approved in 22 countries in Europe. In the United States, ferric derisomaltose was approved in 2020, and in Canada, in the year 2018, by the name of Monoferric. A 1000 mg dose was allowed in a single infusion of ferric derisomaltose, which was the only FDA-approved formulation that allowed this.

Used to treat the symptoms of Iron-deficiency Anemia (IDA), INFeD, which was a prescription medicine containing which is also known as Iron Dextran Injection USP, was used with other medications or alone.

Monoferric Injection USP is injected to treat anemia caused by the deficiency of iron.

FAQ

  1. Is there an injectable form of iron?

Patients who cannot be treated with iron supplements that are made for oral use are prescribed iron dextran injections which come under the class of medications called iron replacement products. This form of medicine replenishes the iron stores of the body of the patient rapidly. Ferric derisomaltose is also a kind of injection that can be prescribed for such situations.

  1. What are the side effects of intravenous iron?

Skin problems include rash, problems with breathing, and gastrointestinal pains including cramps and nausea, lightheadedness, faintness, or dizziness at the time of getting up suddenly from a sitting or a lying position, and swelling or bloating of the feet, lower legs, hands, arms or face are some of the side effects that can be caused with the infusion of intravenous iron. If their side effects last long or have a serious or adverse effect on the health of the patient, then a doctor or a medical expert should be contacted immediately to avoid severe damage.

  1. How long do iron injections last?

The range of the time of infusion is less than 20 minutes to up to 4 hours. The form of iron that has been used decides the side effects that might occur due to the iron infusion. Low blood pressure and nausea are common side effects of iron infusions.

  1. What is iron dextran made of?

Made up of a slightly viscous sterile liquid complex of dextran and ferric hydroxide INFeD, also known as Iron Dextran Injection USP is dark brown and is meant for intramuscular or intravenous use. Each ml of Iron Dextran consists of approximately 0.9% sodium chloride and a 50 mg equivalent of elemental iron which is known as iron dextran complex, in water for injection.

  1. Is Iron Dextran still used?

Iron dextran is no longer used due to the link to rare anaphylactic reactions which causes anaphylaxis that might be caused due to the usage.

  1. What is ferric derisomaltose used for?

Ferric derisomaltose replaces the use of iron dextran in the treatment of iron deficiency anemia as an iron replacement product in patients with nondialysis-dependent chronic kidney disease (CKD), and in patients who are allergic to oral supplements of iron or the oral iron supplements didn’t work.

  1. Is Iron isomaltoside the same as ferric derisomaltose?

Ferric derisomaltose is the name given to iron isomaltoside 1000. The United States adopted the name Ferric derisomaltose which was also considered to be the international nonproprietary name, whereas iron isomaltoside 1000 is the generic name initially approved in the European Union.

  1. Can iron infusion harm an unborn baby?

The safety and effectiveness of intravenous iron have been approved and published in the evidence reports even in the second and third trimesters of pregnancy. The oral intolerance or ineffectiveness can lead to a severe condition in which iron supplementation is needed to be pushed through, using intravenous or intramuscular injections.

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