Intravenous iron infusion | |
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Other names | IV iron infusion, IV infusion |
Specialty | hematology |
Intravenous (IV) iron infusion is a therapy in which a combination of iron and saline solution is delivered directly into the bloodstream through a vein, in patients suffering iron deficiency, iron-deficiency anaemia and chronic kidney disease. [1] [2] [3] IV iron infusions are recommended when oral iron supplementation fails to adequately restore iron and haemoglobin levels in the blood. The intravenous method is a fast and effective way of delivering iron throughout the body, used as iron can be administered instantly rather than gradually over time.
IV iron infusions first came about in the early twentieth century. The earliest intravenous iron solution was ferric hydroxide. Treatment was only recommended in extreme conditions due to its association with toxicity. [4] Ferric hydroxide was identified as toxic because it was found to release free bioactive iron when injected intravenously, increasing risk of infection.
Further research led to the development of iron saccharide in 1947. Testing concluded iron saccharide to be safer and more effective for anaemic patients seeking a IV infusion. [4] Later, in 1954 the use of iron dextran became popular and a product called Imferon emerged. Release of free bioactive iron was minimised by covering the iron oxide core in large dextran molecules. [4] Patients responded well to Imferon, a rapid increase in haemoglobin and iron levels was observed and researchers saw a low incident of side effects compared to previous iron solutions. [4] Large dextran molecules did however have a connection to anaphylaxis. As such an infusion of Imferon was not recommended to patients with a history of allergic reactions, and a test dose was required for all other patients undergoing treatment. [5]
In 1980 a study was completed in the United States on the clinical use of intravenous iron infusions. Four hundred and seventy-one patients with iron deficiency were treated with IV iron infusions at varying doses. [4] Three patients suffered anaphylactic reactions such as drop in blood pressure, discolouration of the skin, shortness of breath and fainting. [4] Researchers concluded that IV infusions should only be used in circumstances were oral iron supplements could not be taken.
Products such as Imferon, which contained high molecule weight iron dextran, were the only IV iron products available until the 1990s. [4] Although uncommon adverse reaction did occur, as such packaging informed users of the possible reactions and highly recommended completing a test dose before further treatment. In 1991 a worldwide recall of high molecule weight iron dextran was enforced after a contaminated batch was leaked. [4] In 1992 it was removed from the market and manufacturing ceased. During this time low molecular weight iron dextran was introduced and released for clinical use in 1992. [4] The use of low molecule weight iron dextran was common place for renal dialysis patients and due to its success usage increased progressively through to 1997. [4]
In 1999, a new compound ferric gluconate was introduced in the form of Ferrlecit. [6] Ferric gluconate was determined to be a safer alternative to iron dextran products with lower rates of serious adverse effects. [6] Iron dextran attributed to at least thirty-one deaths across the United States and Europe, ferric gluconate had no casualty rates. [4] In November 2000, iron sucrose was introduced in the United States after it has been long used in Europe [4] Similar to ferric gluconate, iron sucrose did not require a dextran coat thus minimising risk associated with anaphylaxis. Progressively over time intravenous iron infusions have begun to play a significantly role in the treatment of anaemia specifically in the fields of hematology and oncology. [6]
In recent years, three new IV iron compounds have been released. These include, Ferrinject, Iron Isomaltoside and Ferumoxytol. All three of these forms of iron can be injected intravenously restoring blood and iron levels in less than fifteen minutes. [4]
Iron deficiency is one of the most common nutritional deficiencies affecting up to two billion people worldwide. [7] Iron deficiency commonly occurs in patients suffering chronic infection. Intravenous iron infusions are used to treat patients with iron deficiency, iron-deficiency anaemia and chronic kidney disease. IV iron infusions are administered to patients who cannot use oral supplementation to treat their deficiency, or if oral treatment has proven ineffective. [8]
Oral iron supplementations are the first line of care for iron deficiency and iron deficiency anaemia. Anaemic patients are treated with iron tablets containing 100 mg to 200 mg of iron. [7] Oral iron tablets are not easily tolerated and may cause nausea, vomiting, abdominal pain, constipation and diarrhoea. [7] The oxidative properties of iron conflict with the gastrointestinal tract prohibiting proper absorption of iron into the blood. [7] Disorders affecting the gut lead to resistance against oral supplements. [8] Side effects of constipation or diarrhoea are more common with the use of oral iron than intravenous iron. [7] The adverse effects associated with oral iron supplements prohibit patients from completing the full course of medication. [9]
Intravenous iron infusions are prescribed when gastrointestinal absorption is poor or when an urgent increase in haemoglobin levels is required for severely anaemic patients, such as women in their second and third trimester of pregnancy. [7] Iron deficiency anaemia affects forty-two percent of pregnant women. [10] Intravenous iron infusions are a form of treatment for pregnant women that ensures a fast and early recovery. [11] Pregnant women are more likely to successfully replenish iron stores and increase their haemoglobin levels with intravenous iron compared to oral iron supplements. [10] Recovery is reached faster and with fewer side effects than oral iron. [10] Intravenous iron is proven to be very effective for pregnant women with iron deficiency anaemia but not necessarily more effective than oral supplements for those with iron deficiency alone. [9]
The type of iron supplement used depends on the patient's specific condition. The degree and severity of anaemia, tolerability to previous treatment and history of allergy must all be considered before intravenous iron is administered. [7] Correction of iron deficiency with oral iron supplements is particularly ineffective when a patient suffers from a coexisting medical condition. [12] Intravenous iron therapy has an established role in the treatment of iron deficiency anaemia when oral supplements are ineffective or cannot be used. [12] IV iron infusions can administer the exact dose of iron to normalise levels in the blood. [7] Pre-operative anaemia is associated with high risk of death. Intravenous iron infusions can optimise haemoglobin levels, significantly reducing mortality rates. IV iron is found to be highly effective for patients with chronic kidney disease when combined with erythropoiesis stimulating agents. [7] Recent studies of iron and its associated with red blood cells has increased interest in the use and development of intravenous iron therapy to reduce the requirement for allogenic red blood cell transfusions. [13] [12] These findings show that intravenous iron has a broad use to many patients where anaemia is an underlying issue. [12]
Intravenous therapy is a type of parenteral medication. IV iron infusion is a method of delivering a mixed solution of iron and saline from a drip through a needle directly into the vein and bloodstream. [14] The procedure takes place in a medical clinic and may take several hours depending on the iron preparation that has been prescribed. The patient will receive infusions over the course of several visits until iron stores have been fully replenished. [4]
Patients temperature, blood pressure, pulse and breathing rate are monitored constantly for signs of immediate hypersensitivity during and thirty minutes after treatment. [14] Adverse reactions can be reduced further by premedication, antihistamines and test dosages. [5] Blood tests are taken two to four weeks post treatment, to assess if iron stores have been successfully replenished. [14]
There are five types of iron compounds used for IV iron infusion. The iron preparation used is chosen to specifically match the patient's individual needs. Each treatment differs in the duration of their administration, the approved dosage and the concentration of iron.
Name | DexFerrum | INFeD | Ferrlecit | Venofer | Feraheme | Monofer | Ferinject |
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Manufacturer | American Regent Inc. | Watson Pharmaceuticals Inc. | Sanofi Aventis Inc. | American Regent Inc. | AMAG Pharmaceuticals | Pharmacosmos A/s | American Regent Inc. |
Iron Compound | Iron Dextran | Iron Dextan | Iron Sucrose | Iron Sucrose | Ferumoxytol | Iron Isomaltoside | Iron Carboxymaltose |
Molecular weight | 265 000 high molecular weight iron dextran | 165 000 low molecular weight iron dextran | 289 000 - 444 000 | 34 000 - 60 000 | 750 000 | 150 000 | 150 000 |
Maximum approved dosage (mg) | 100 | 100 | 125 | 200 | 510 | 20 mg per kg | 1000 mg if patient weight is > 66 kg |
Test dose required | Yes | Yes | No | No | No | No | No |
Iron concentration (mg/mL) | 50 | 50 | 12.5 | 20 | 30 | 100 | 50 |
Venofer is used for iron deficiency and anaemia in patients with chronic kidney disease. [15] DexFerrum, INFeD and Ferinject are iron preparations prescribed to patients who cannot tolerate oral iron supplements or if oral iron has proven ineffective in replenishing iron levels in the blood. [16] [17] [18] Feraheme is used for both patients who found oral administration to be ineffective and to treat anaemia in patients with chronic kidney disease. [19] Monofer is prescribed to patients who require an urgent and rapid build-up of iron stores and haemoglobin in the blood. [20]
Some iron preparations can trigger anaphylaxis in patients with certain allergies. Serious hypersensitivity including anaphylactic reactions have been reported with the use of high molecular weight iron dextran for intravenous iron infusions. [12] The use of high molecular weight iron dextran has now been abandoned. Patients using Venofer for iron deficiency and anaemia in chronic kidney disease have reported experiences of hypotension, shock and loss of consciousness. [15] Newer preparations have largely alleviated any association with anaphylaxis. [12] The risk of hypersensitivity with the use of iron sucrose being one in five thousand. [8] Medicines are prescribed to patients who have experienced hypersensitive reactions to IV iron infusions in the past to prevent this from reoccurring. [21] Simple recommendations to minimise the risk is slow administration accompanied by careful patient monitoring during and after the infusion. [7]
Any form of intravenous infusion carries the risk of infection. Risk is heightened when the equipment being used is not properly sterilised. In intravenous iron infusions, free iron has been shown to potentiate bacterial growth. [12] Evidence associated with intravenous iron therapy and infection is inconclusive. Newer intravenous iron preparations with low free iron concentrations limit the potential risk of infection. [12] It is advised that iron preparations with high free iron concentrations are avoided.
Intravenous iron infusions can cause skin rash, hives, itchiness and flush. Skin staining and discolouration can occur at the site of infusion if the iron and saline solution leaks outside the vein into the surrounding tissue. [14] Skin discolouration can be semi-permanent or permanent.
Patients are at risk of hypothermia since large amounts of cold fluid are being infused directly into the bloodstream at a rapid rate. This dramatic change in temperature may prompt other side effects such as chest pain, irregular breathing and muscles aches and pains.
Patients may experience pains and aches of the muscles, specifically in areas near the spine. Myalgia side effects can occur up to one or two days after the treatment takes place.
IV iron infusions can induce hypophosphatemia by raising plasma levels of the phosphaturic hormone FGF-23. Such reactions more often occur after iron carboxymaltose than after other i. v. iron compounds.
IV iron infusions can trigger dyspnoea, wheezing and chest pain in patients who suffer from asthma.
IV infusions can bring on nausea, diarrhoea, abdominal pain or cramps and vomiting.
Anemia or anaemia is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to a lower than normal number of red blood cells, a reduction in the amount of hemoglobin available for oxygen transport, or abnormalities in hemoglobin that impair its function. The name is derived from Ancient Greek ἀν- (an-) 'not', and αἷμα (haima) 'blood'. When anemia comes on slowly, the symptoms are often vague, such as tiredness, weakness, shortness of breath, headaches, and a reduced ability to exercise. When anemia is acute, symptoms may include confusion, feeling like one is going to pass out, loss of consciousness, and increased thirst. Anemia must be significant before a person becomes noticeably pale. Additional symptoms may occur depending on the underlying cause. Anemia can be temporary or long term and can range from mild to severe.
Iron deficiency, or sideropenia, is the state in which a body lacks enough iron to supply its needs. Iron is present in all cells in the human body and has several vital functions, such as carrying oxygen to the tissues from the lungs as a key component of the hemoglobin protein, acting as a transport medium for electrons within the cells in the form of cytochromes, and facilitating oxygen enzyme reactions in various tissues. Too little iron can interfere with these vital functions and lead to morbidity and death.
Intravenous therapy is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrients for those who cannot, or will not—due to reduced mental states or otherwise—consume food or water by mouth. It may also be used to administer medications or other medical therapy such as blood products or electrolytes to correct electrolyte imbalances. Attempts at providing intravenous therapy have been recorded as early as the 1400s, but the practice did not become widespread until the 1900s after the development of techniques for safe, effective use.
Iron-deficiency anemia is anemia caused by a lack of iron. Anemia is defined as a decrease in the number of red blood cells or the amount of hemoglobin in the blood. When onset is slow, symptoms are often vague such as feeling tired, weak, short of breath, or having decreased ability to exercise. Anemia that comes on quickly often has more severe symptoms, including confusion, feeling like one is going to pass out or increased thirst. Anemia is typically significant before a person becomes noticeably pale. Children with iron deficiency anemia may have problems with growth and development. There may be additional symptoms depending on the underlying cause.
Hypoparathyroidism is decreased function of the parathyroid glands with underproduction of parathyroid hormone (PTH). This can lead to low levels of calcium in the blood, often causing cramping and twitching of muscles or tetany, and several other symptoms. It is a very rare disease. The condition can be inherited, but it is also encountered after thyroid or parathyroid gland surgery, and it can be caused by immune system-related damage as well as a number of rarer causes. The diagnosis is made with blood tests, and other investigations such as genetic testing depending on the results. The primary treatment of hypoparathyroidism is calcium and vitamin D supplementation. Calcium replacement or vitamin D can ameliorate the symptoms but can increase the risk of kidney stones and chronic kidney disease. Additionally, medications such as recombinant human parathyroid hormone or teriparatide may be given by injection to replace the missing hormone.
Dextran is a complex branched glucan, originally derived from wine. IUPAC defines dextrans as "Branched poly-α-d-glucosides of microbial origin having glycosidic bonds predominantly C-1 → C-6". Dextran chains are of varying lengths.
Microcytic anaemia is any of several types of anemia characterized by smaller than normal red blood cells. The normal mean corpuscular volume is approximately 80–100 fL. When the MCV is <80 fL, the red cells are described as microcytic and when >100 fL, macrocytic. The MCV is the average red blood cell size.
Anemia of chronic disease (ACD) or anemia of chronic inflammation is a form of anemia seen in chronic infection, chronic immune activation, and malignancy. These conditions all produce elevation of interleukin-6, which stimulates hepcidin production and release from the liver. Hepcidin production and release shuts down ferroportin, a protein that controls export of iron from the gut and from iron storing cells. As a consequence, circulating iron levels are reduced. Other mechanisms may also play a role, such as reduced erythropoiesis. It is also known as anemia of inflammation, or anemia of inflammatory response.
Iron supplements, also known as iron salts and iron pills, are a number of iron formulations used to treat and prevent iron deficiency including iron deficiency anemia. For prevention they are only recommended in those with poor absorption, heavy menstrual periods, pregnancy, hemodialysis, or a diet low in iron. Prevention may also be used in low birth weight babies. They are taken by mouth, injection into a vein, or injection into a muscle. While benefits may be seen in days, up to two months may be required until iron levels return to normal.
Calcium gluconate is the calcium salt of gluconic acid and is used as a mineral supplement and medication. As a medication it is used by injection into a vein to treat low blood calcium, high blood potassium, and magnesium toxicity. Supplementation is generally only required when there is not enough calcium in the diet. Supplementation may be done to treat or prevent osteoporosis or rickets. It can also be taken by mouth but is not recommended for injection into a muscle.
Management of ulcerative colitis involves first treating the acute symptoms of the disease, then maintaining remission. Ulcerative colitis is a form of colitis, a disease of the intestine, specifically the large intestine or colon, that includes characteristic ulcers, or open sores, in the colon. The main symptom of active disease is usually diarrhea mixed with blood, of gradual onset which often leads to anaemia. Ulcerative colitis is, however, a systemic disease that affects many parts of the body outside the intestine.
Treprostinil, sold under the brand names Remodulin for infusion, Orenitram for oral, and Tyvaso for inhalation, is a vasodilator that is used for the treatment of pulmonary arterial hypertension. Treprostinil is a synthetic analog of prostacyclin (PGI2).
Paricalcitol (chemically it is 19-nor-1,25-(OH)2-vitamin D2. Marketed by Abbott Laboratories under the trade name Zemplar) is a drug used for the prevention and treatment of secondary hyperparathyroidism (excessive secretion of parathyroid hormone) associated with chronic kidney failure. It is an analog of 1,25-dihydroxyergocalciferol, the active form of vitamin D2 (ergocalciferol).
Pharmacosmos is a pharmaceutical company specialized in treatment of iron deficiency anemia.
Sodium ferric gluconate complex, sold under the brand name Ferrlecit, is an intravenously administered iron medication for the treatment of iron deficiency anemia in adults and in children aged six years and older with chronic kidney disease receiving hemodialysis who are receiving supplemental epoetin therapy. The macromolecule has an apparent molecular weight of 289,000–440,000 Dalton.
Intravenous iron sucrose is a commonly used treatment for iron deficiency anemia. Iron sucrose replaces iron in the blood to foster red blood cell production in patients with chronic kidney disease. Iron sucrose has the trade name Venofer.
Immunoglobulin therapy is the use of a mixture of antibodies to treat several health conditions. These conditions include primary immunodeficiency, immune thrombocytopenic purpura, chronic inflammatory demyelinating polyneuropathy, Kawasaki disease, certain cases of HIV/AIDS and measles, Guillain–Barré syndrome, and certain other infections when a more specific immunoglobulin is not available. Depending on the formulation it can be given by injection into muscle, a vein, or under the skin. The effects last a few weeks.
Anemia is a condition in which blood has a lower-than-normal amount of red blood cells or hemoglobin. Anemia in pregnancy is a decrease in the total red blood cells (RBCs) or hemoglobin in the blood during pregnancy. Anemia is an extremely common condition in pregnancy world-wide, conferring a number of health risks to mother and child. While anemia in pregnancy may be pathologic, in normal pregnancies, the increase in RBC mass is smaller than the increase in plasma volume, leading to a mild decrease in hemoglobin concentration referred to as physiologic anemia. Maternal signs and symptoms are usually non-specific, but can include: fatigue, pallor, dyspnea, palpitations, and dizziness. There are numerous well-known maternal consequences of anemia including: maternal cardiovascular strain, reduced physical and mental performance, reduced peripartum blood reserves, increased risk for peripartum blood product transfusion, and increased risk for maternal mortality.
Ferric maltol, sold under the brand names Accrufer (US) and Feraccru (EU), is an iron containing medication for the treatment of adults with low iron stores. It is taken by mouth.
Iron preparation is the formulation for iron supplements indicated in prophylaxis and treatment of iron-deficiency anemia. Examples of iron preparation include ferrous sulfate, ferrous gluconate, and ferrous fumarate. It can be administered orally, and by intravenous injection, or intramuscular injection.