Iron dextran administration

The adverse effects of iron formulations have resulted in trials to optimize dose regimens. A large database of clinical variance reports from Fresenius Medical Care North America (FMCNA) has been analysed to determine the incidence of suspected adverse drug reactions of iron dextran and the associated patient characteristics, dialysis practice patterns, and outcomes (8). A case-cohort design was used, comparing individuals who had suspected adverse drug reactions with the overall population. Out of 841 252 intravenous iron dextran administrations over 6 months, there were 165 reported suspected adverse drug... 

However, toxic reactions to intravenous iron occur when ionized iron exceeds plasma binding capacity. With iron dextran, the iron moiety is so firmly bound to dextran that ionized iron does not exceed plasma ironbinding capacity even when total plasma iron concentrations are extremely high. However, there are adverse effects, which were at first underestimated whenever possible other routes or methods of iron dextran administration should be preferred. 

In one case iron dextran administration falsely reduced total serum calcium concentration and increased the phosphorus concentration (58). 

Sloand JA, Shelly MA, Erenstone AL, Schiff Ml, Talley TE, Dhakal MP. Safety and efficacy of total dose iron dextran administration in patients on home renal replacement therapies. Perit Dial Int 1998 18(5) 522-7. 

Go RS, Porrata LF, Call TG. Thrombocytopenia after iron dextran administration in a patient with severe iron deficiency anemia. Ann Intern Med 2000 132(11) 925. 

Gilbert, L., Dean, R. E., and Karaganis, A., 1979, Iron dextran administration via TPN solution in malnourished patients with low serum transferrin levels, J. Parent. Enter. Nutr. 3 509. 

Iron dextran is a parenteral iron that is also used for die treatment of iron deficiency anemia It is primarily used when the patient cannot take oral drugs or when the patient experiences gastrointestinal intolerance to oral iron administration. Other iron preparations, both oral and parenteral, used in the treatment of iron deficiency anemia can be found in the Summary Drug Table Dragp Used in the Treatment of Anemia... 

Iron salts occasionally cause gastrointestinal irritation, nausea, vomiting, constipation, diarrhea, headache, backache, and allergic reactions. The stools usually appear darker (black). Iron dextran is given by the parenteral route Hypersensitivity reactions, including fatal anaphylactic reactions, have been reported with the use of this form of iron. Additional adverse reactions include soreness, inflammation, and sterile abscesses at the intramuscular (IM) injection site Intravenous (IV) administration may result in phlebitis at the injection site When iron is administered via the IM route, a brownish discoloration of tlie skin may occur. Fhtients with rheumatoid arthritis may experience an acute exacerbation of joint pain, and swelling may occur when iron dextran is administered. 

Parenteral iron therapy currently is available in three different formulations, which are listed in Table 63-3. Iron dex-tran was the first parenteral iron formulation to be approved, followed by ferric gluconate, and then iron sucrose. Although these newer agents are only approved by the Food and Drug Administration (FDA) to treat anemia associated with CKD in patients receiving erythropoietin products, they are effective in treating iron-deficiency anemia as well. Iron dextran is FDA approved for treating documented iron deficiency in patients who are unable to tolerate the oral formulation. 

The average adult body contains approximately 4 g of iron, of which roughly two-thirds exists in the form of hemoglobin. Treatment of certain types of anemias usually consists of dietary supplementation or the administration of therapeutic iron preparations by oral and parenteral routes. Iron is often administered by i.m. as iron-dextran complex which is ferric hydroxide and dextran containing 50 mg of iron per milliliter. 

The parenteral use of complexes of iron and carbohydrates has resulted in anaphylactic-type reactions. Deaths associated with such administration have been reported therefore, use iron dextran injection only in those patients in whom the indications have been clearly established and laboratory investigations confirm an iron-deficient state not amenable to oral iron therapy. Because fatal anaphylactic reactions have been reported after administration of iron dextran injection, administer the drug only when resuscitation techniques and treatment of anaphylactic and anaphylactoid shock are readily available. 

Hypersensitivity reactions Anaphylaxis and other hypersensitivity reactions have been reported after uneventful test doses as well as therapeutic doses of iron dextran injection. Therefore, consider administration of subsequent test doses during therapy. Have epinephrine immediately available in the event of acute hypersensitivity reactions. 

Arthritis Patients with rheumatoid arthritis may have an acute exacerbation of joint pain and swelling following administration of iron dextran. 

Drug/Lab test interactions Large doses of iron dextran (5 mL or more) give a brown color to serum from a blood sample drawn 4 hours after administration they may cause falsely elevated values of serum bilirubin and falsely decreased values of serum calcium. 

The symptoms of iron deficiency anemia include fatigue, weakness, shortness of breath, and soreness of the tongue. Therapeutic iron supplementation is used to treat this type of anemia. Oral administration of ferrous salts (generic ferrous sulfate, Feosol, Slo Fe) is preferred, but parenteral iron (iron dextran, InfeD) can be given if oral therapy fails. Toxic reactions occur more frequently after parenteral iron administration. Gastrointestinal disturbances are common following oral dosages. 

The challenge with parenteral iron therapy is that parenteral administration of inorganic free ferric iron produces serious dose-dependent toxicity, which severely limits the dose of that can be administered. However, when the ferric iron is formulated as a colloid containing particles with a core of iron oxyhydroxide surrounded by a core of carbohydrate, bioactive iron is released slowly from the stable colloid particles. In the USA, the three available forms of parenteral iron are iron dextran, sodium ferric gluconate complex, and iron sucrose. 

Iron dextran is a stable complex of ferric oxyhydroxide and dextran polymers containing 50 mg of elemental iron per milliliter of solution. It can be given by deep intramuscular injection or by intravenous infusion, although the intravenous route is used most commonly. Intravenous administration eliminates the local pain and tissue staining that often occur... 

The richest dietary sources of total iron are organ meats (liver and kidney), egg yolk, dried legumes, com, molasses and parsley. Liver is particularly valuable because of the high absorbability of its iron. However, only about 10% of dietary iron is absorbed. Iron deficiency anemia can be treated with soluble iron(II) compounds providing 200 mg in three or four daily divided doses. Oral iron(II) sulfate is the least expensive and is in wide use. Ascorbic acid increases the absorption efficiency of iron(II) sulfate. Parenteral administration of iron is used when oral iron is ineffective. Iron-dextran, a colloid formed from iron(III) chloride and an alkali-modified dextran, is one of several preparations available which has found extensive clinical use. It contains up to 28% Fe by weight and has a structural similarity to ferritin. Transfusion therapy may also be used in severe chronic anemia or acute hemorrhage. 

Most adults with iron deficiency anemia require 1-2 g of replacement iron, or 20-40 mL of iron dextran. Most physicians prefer to give the entire dose in a single intravenous infusion in several hundred milliliters of normal saline over 1-2 hours. Intravenous administration eliminates the local pain and tissue staining that often occur with the intramuscular route and allows delivery of the entire dose of iron necessary to correct the iron deficiency at one time. There is no clear evidence that any of the adverse effects, including anaphylaxis, are more likely to occur with intravenous than with intramuscular administration. 

Methods for the depolymerization of dextran to uniform fractions of lower molecular weight have led to the use of two dextran fractions that are suitable for parenteral administration.13,30 In the United States, a dextran fraction of MW 70,000 is used as a blood-volume expander. Clinical dextran is used to restore blood volume in the treatment of patients who have either lost considerable amounts of blood or are in shock. A dextran fraction of MW 40,000 is used to improve the flow in capillaries, to prevent or treat vascular occlusion, and to perfuse organs artifically. B-512(F) dextran is completely metabolized141 in man when fractions are administered parentally. Various dextran fractions have been used to prepare numerous derivatives,29 such as the sulfates, and 0-(2-diethylaminoethyl) (DEAE)-dextran, and complexes with various metals. Dextran sulfates have anticoagulant,340 antilipemic,340 and anti-ulcer341 activity. A soluble, iron-dextran complex342 of MW 5000 is used to alleviate iron-deficiency anemia, and a calcium complex332 alleviates hypocalcemia of cattle. 

When used in patients without iron overload, deferoxamine can cause iron deficiency (12). In 20 patients, there were falls in ferritin concentrations in six, requiring withdrawal of deferoxamine and parenteral administration of iron dextran (12). Monitoring ferritin concentrations is therefore recommended in patients receiving deferoxamine for aluminium overload. On the other hand, the administration of deferoxamine (500mg/day by subcutaneous infusion) improves chronic anemia in patients with rheumatoid arthritis (77). This effect is thought to be achieved through increased erythropoietin responsiveness, secondary to iron chelation. Iron chelation with deferoxamine also improves hemopoiesis in patients with myelodysplastic syndromes and can reduce transfusion dependency (78). Exactly how deferoxamine works in these patients remains to be explained. 

Iron compounds for intramuscular administration are iron sorbitol-citric acid complex (iron sorbitex), iron dextran, iron glycerin-citric acid complex, and iron poljdso-maltose. The work on these formulations is largely old and has been reviewed in previous volumes in this series. 

IV iron regimen may be divided over 8-10 HD sessions (depending on product used) or given in larger doses (eg, up to 500 mg iron dextran, 300 mg iron sucrose, 250 mg ferric gluconate) over a prolonged administration time for patients with early CKD or on PD. 

Administration of 1 g of IV iron is reasonable to initially replete patients with an absolute iron deficiency (TSat <20%, serum ferritin < 100 ng/mL) however, many patients become iron deficient quickly without ongoing iron supplementation. There is sufficient evidence to support use of maintenance doses of IV iron (e.g., iron sucrose or iron dextran 25 to 100 mg/wk sodium ferric gluconate 62.5 to 125 mg/wk), particularly in hemodialysis patients. ... 

When iron dextran is given IV, the iron is taken up immediately by the reticuloendothelial system. Small to intermediate IV doses (50 to 500 mg of elemental iron) can be cleared from the plasma within 3 days of administration. In contrast, larger IV doses of iron dextran (500 mg of elemental iron) are processed by the reticuloendothelial system at a constant rate of 10 to 20 mg/h. Doses this large are associated with increased plasma concentrations of iron dextran for as long as 3 weeks. 

The iron dextran package insert carries a black box warning regarding the risk of anaphylaxis and requires a test dose before administration of the repletion dose. Methods of IV administration include multiple slow injections of undiluted iron dextran solution or an infusion of a diluted preparation. This latter method is often referred... 

Equations for calculating the appropriate dose of parenteral iron in patients with IDA or those with anemia secondary to blood loss can be found in Table 99-7. When given by IV administration, the dose should not exceed 50 mg of iron per minute (1 mL/min). It is suggested that all patients considered for an iron dextran injection receive a test dose of 25 mg IM or IV, or a 5- to 10-minute infusion of the diluted solution. Patients should then be observed for more than 1 hour for untoward reactions. If an anaphylaxis-like reaction were to occur, it generally responds to IV epinephrine, diphenhydramine, and corticosteroids. Patients receiving total dose infusions can have the remaining solution infused during the next 2 to 6 hours if the test dose is tolerated. 

Iron dextran is an iron product that replenishes hemoglobin and depleted iron stores. It is indicated in the treatment of iron deficiency anemia when oral administration of iron is unsatisfactory or impossible. 

Iron dextran injection (INFED, DEXFERRUM) is a colloidal solution of ferric oxyhydroxide com-plexed with polymerized dextran (molecular weight -ISO IcDa) that contains 50 mg/mL of elemental iron. It can be administered by either intravenous (preferred) or intramuscular injection. When given by deep intramuscular injection, it is gradually mobilized via the lymphatics and transported to reticuloendothelial cells the iron then is released from the dextran complex. Intravenous administration gives a more reliable response. Given intravenously in a dose of less than 500 mg, the iron dextran complex is cleared with a plasma tj of 6 hours. When I g or more is administered intravenously as total dose therapy, reticuloendothelial cell clearance is constant at 10-20 mg/h. This slow rate of clearance results in a brownish discoloration of the plasma for several days and an elevation of the serum iron for 1-2 weeks. 

An iron dextran infusion must be administered and closely monitored. The nurse must treat the client with a life-threatening dysrhythmia before being able to devote time to the administration of the medication. 

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