Iron therapy administration

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. 

Although EPO deficiency is the primary cause of CKD anemia, iron deficiency is often present, and it is essential to assess and monitor the CKD patient s iron status (NKF-K/DOQI guidelines). Iron stores in patients with CKD should be maintained so that transferrin saturation (TSAT) is greater than 20% and serum ferritin is greater than 100 ng/mL (100 mcg/L or 225 pmol/L). If iron stores are not maintained appropriately, epoetin or darbepoetin will not be effective, and most CKD patients will require iron supplementation. Oral iron therapy can be used, but it is often ineffective, particularly in CKD patients on dialysis. Therefore, intravenous iron therapy is used extensively in these patients. Details of the pharmacology, pharmacokinetics, adverse effects, interactions, dose, and administration of erythropoietin and iron products have been discussed previously. 

Diet plays a significant role because iron is poorly absorbed from vegetables, grain products, dairy products, and eggs iron is best absorbed from meat, fish, and poultry. Administration of iron therapy with a meal decreases absorption by more than 50% but may be needed to improve tolerability. 

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. 

Monitoring Exercise caution to withhold iron administration in the presence of evidence of tissue iron overload. Periodically monitor hematologic and hematinic parameters (hemoglobin, hematocrit, serum ferritin, and transferrin saturation). Withhold iron therapy in patients with evidence of iron overload. Transferrin saturation values increase rapidly after IV administration of iron sucrose thus, serum iron values may be reliably obtained 48 hours after IV dosing. 

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. 

For patients who are treated chronically with parenteral iron, it is important to monitor iron storage levels to avoid the serious toxicity associated with iron overload. Unlike oral iron therapy, which is subject to the regulatory mechanism provided by the intestinal uptake system, parenteral administration, which bypasses this regulatory system, can deliver more iron than can be safely stored. Iron stores can be estimated on the basis of serum concentrations of ferritin and the transferrin saturation, which is the ratio of the total serum iron concentration to the total iron-binding capacity ( ). 

Like oral iron, parenteral iron is used too widely. When iron is truly needed, oral administration is generally preferable (9). Intractable gastrointestinal intolerance to oral formulations, hyperemesis in pregnancy, very severe blood loss, and possibly ulcerative colitis are some of the few valid indications for parenteral iron. A low ironbinding capacity (for example due to prior saturating iron therapy or malnutrition), folic acid deficiency, and an allergic constitution predispose the patient to adverse reactions to parenteral iron. Iron injections have been reported to provoke hemolytic anemia in cases of paroxysmal nocturnal hemoglobinuria. 

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. 

I Efficacy. While supplementation using oral preparations may seem more practical than IV administration, oral iron therapy is lim-... 

Intravenous iron therapy is an effective means to prevent iron deficiency and maintain adequate iron status for erythropoiesis. Parenteral iron improves the responsiveness to erythropoietic therapy and reduces the dose required to achieve and maintain the target Hgb/Hct. Iron administration in patients with what is known as a functional iron deficiency is more questionable. Functional iron deficiency is characterized by a low TSat (<20%) in the presence of a normal or elevated serum ferritin. In other words, there may appear to be adequate storage iron, but iron is not being carried by transferrin to the bone marrow for red blood cell production. If the Hgb is less than the target of II g/dL, under these conditions a trial of IV iron therapy may be warranted. Iron supplementation alone may improve Hgb/Hct and may... 

In most cases of IDA, oral administration of iron therapy with soluble Fe + iron salts is appropriate. ... 

Most patients tolerate EPO therapy well. Iron deficiency can occur in patients treated with EPO and close monitoring of iron levels is necessary. Oral iron supplementation should be given if transferrin saturation drops to 20% or the serum ferritin level drops below 100 ng/mL. Some patients develop functional iron deficiency, in which the iron stores are normal, but the supply of iron to the erythroid marrow is less than that necessary to support the demand for RBC production. Therefore many practitioners routinely supplement EPO therapy with oral iron therapy. The hypertension commonly seen in end-stage renal disease patients on EPO is far less common in AIDS patients. More common toxicities of EPO administration include nausea, headache, fever, bone pain, and fatigue. Other adverse effects to monitor include seizures, thrombotic events, and allergic reactions such as rash or local reactions at the injection site. 

When oral iron therapy fails, parenteral iron administration may be an effective alternative. The rate of response to parenteral therapy is similar to that which follows usual oral doses. Common indications are iron malabsorption (e.g., sprue, short bowel syndrome), severe oral iron intolerance, as a rontine supplement to total parenteral nntrition, and in patients who are receiving erythropoietin. 

Promoting an Optimal Response to Therapy IRON Iron salts are preferably given between meals widi water but can be given with food or meals if gastrointestinal upset occurs. If die patient is receiving odier drugp, the nurse checks with the hospital pharmacist regarding die simultaneous administration of iron salts with other dru . ... 

Anaemia often becomes a characteristic feature of several chronic diseases, such as rheumatoid arthritis. In most instances this can be linked to lower than normal endogenous serum EPO levels (although in some cases a deficiency of iron or folic acid can also represent a contributory factor). Several small clinical trials have confirmed that administration of EPO increases haematocrit and serum haemoglobin levels in patients suffering from rheumatoid arthritis. A satisfactory response in some patients, however, required a high-dose therapy that could render this therapeutic approach unattractive from a cost benefit perspective. 

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. 

The high efficiency and selectivity of the natural siderophores in binding iron(lll) inspired attempts to develop siderophore analogs with improved iron-scavenging properties amenable for chelation therapy. A most pertinent example is desferrioxamine B (DFO), where low patient compliance generates the need for developing oral means of administration for... 

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. 

Rapid intravenous administration may result in hypotension. Adverse idiosyncratic responses such as flushing, abdominal discomfort, and rash have also been observed. Pulmonary complications (eg, acute respiratory distress syndrome) have been reported in some patients undergoing deferoxamine infusions lasting longer than 24 hours, and neurotoxicity and increased susceptibility to certain infections (eg, with Yersinia enterocolitica) have been described after long-term therapy of iron overload conditions (eg, thalassemia major). 

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. 

The term modified covers several drug delivery systems. Delayed-release available other than immediately after administration (mesalazine in the colon) sustained-release slow release as governed by the delivery system (iron, potassium) controlied-release at a constant rate to maintain unvarying plasma concentration (nitrate, hormone replacement therapy). 

Tetracyclines and Metals. Tetracyclines can combine with metal ions, such as calcium, magnesium, aluminum, and iron, in the GI tract to form complexes that are poorly absorbed. Thus, the simultaneous administration of certain drugs (e.g., antacids, iron preparations, products containing calcium salts) by patients on tetracycline therapy could result in a significant decrease in the amount of antibiotic absorbed. When two drugs are recognized as having a potential to interact, there is sometimes a tendency to believe that one of them should be discontinued. In the case of the tetracycline antacid interactions, problems can be... 

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