Iron therapy adverse effects

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. 

Iron-deficiency anemia in chronic PN patients may be due to underlying clinical conditions and the lack of iron supplementation in PN. Parenteral iron therapy becomes necessary in iron-deficient patients who cannot absorb or tolerate oral iron. Parenteral iron should be used with caution owing to infusion-related adverse effects. A test dose of 25 mg of iron dextran should be administered first, and the patient should be monitored for adverse effects for at least 60 minutes. Intravenous iron dextran then may be added to lipid-free PN at a daily dose of 100 mg until the total iron dose is given. Iron dextran is not compatible with intravenous lipid emulsions at therapeutic doses and can cause oiling out of the emulsion. Other parenteral iron formulations (e.g., iron sucrose and ferric gluconate) have not been evaluated for compounding in PN and should not be added to PN formulations. 

Adverse effects consist mainly of gastrointestinal intolerance such as nausea, epigastric pain and diarrhea and, especially in the elderly constipation with continued therapy. All ferrous salts may cause a black coloration of the faeces. Children are particularly susceptible to potentially lethal iron intoxications. Oral iron preparations should not be administered concurrently with tetracyclines as mutual interference with absorption will occur. 

After confirmation of iron deficiency iron therapy can be given by oral or parenteral route. Generally oral iron therapy is given unless the patient is suffering from severe anaemia, malabsorption syndrome, gastrectomy or patient is showing adverse effects to oral iron therapy. 

For patients who are unable to tolerate penicillamine, trientine, another chelating agent, may be used in a daily dose of 1-1.5 g. Trientine appears to have few adverse effects other than mild anemia due to iron deficiency in a few patients. Zinc acetate administered orally increases the fecal excretion of copper and is sometimes used for maintenance therapy. The dose is 50 mg three times a day. Zinc sulfate (200 mg/d orally) has also been used to decrease copper absorption. Zinc blocks copper absorption from the gastrointestinal tract by induction of intestinal cell metallothionein. Its main advantage is its low toxicity compared with that of other anticopper agents, although it may cause gastric irritation when introduced. 

The effective oral doses of mifepristone are 100-600 mg, and at any dose the bulk of recipients abort. Of 150 healthy women who received the higher dose, 131 attained a complete abortion. Three women reported bleeding for more than 2 weeks after abortion 16 women had a reduced hemoglobin concentration of under 11 g/dl, justifying iron therapy. Other adverse effects were uterine contractions and pelvic pain (n = 4), transient asthenia (n = 3), and nausea (n = 2) (5). These findings seem to be typical, even though dosage schemes have varied as little as 100 mg orally has been used successfully with similar adverse effects (SED-12,1037 6). 

Adverse effects. Most patients tolerate oral iron therapy but 10-20% have symptoms that may be attributed to iron, generally gastrointestinal upset. These effects of oral iron include nausea, abdominal pain, and either constipation or diarrhoea. Upper GI effects appear to be dose-related and are best managed by ingestion of the tablet with or after food and/or reduction in the amount of iron content in each dose. This will prolong the necessary period of treatment. Diarrhoea or constipation can usually be treated symptomatically without a change in regimen. 

In the following sections, adverse reactions are considered in connection with the types of iron therapy with which they have most commonly been associated, but any adverse effect of iron can in principle occur with any formulation or as a result of mixed medical and nonmedical exposure. 

The safety and efficacy of iron dextran have been evaluated in patients on home renal replacement therapies, without any adverse effects (10). 

Large doses of intravenous iron dextran and iron saccha-rate have been compared in a retrospective study of 379 patients who had attended peritoneal dialysis clinics in the past 5 years (12). Of these, 62 were selected to receive intravenous iron based on ferrokinetic markers of iron deficiency, non-adherence to oral iron, ineffectiveness of oral iron, or increased erythropoietin requirements. Intravenous iron was given as two injections of 500 mg each 1 week apart in 61 patients, 33 of whom received iron dextran, 23 iron saccharate, and five both iron dextran and iron saccha-rate. One patient developed anaphylaxis to a test dose of iron dextran and was excluded from further therapy. Blood samples were collected before and 3 and 6 months after iron infusions. Five of the 34 patients who received iron dextran developed minor adverse effects and one had an anaphylactic reaction to the test dose. Of the 23 patients who received iron saccharate, one had an anaphylactic reaction and two had transient chest pain, which subsided without therapy. There were more adverse effects with iron dextran (7.4% of injections) compared with iron saccharate (4.3% of injections), but this difference was not statistically significant. The number of episodes of peritonitis also increased during the 6 months after intravenous iron infusion, especially with iron dextran, compared with the number of episodes during the 6 months before iron infusions, although the difference was not statistically significant. 

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. 

Adverse effects of oral iron preparations are that they cause gastrointestinal irritation including nausea, epigastric pain, diarrhoea and/or constipation. Parenteral preparations are available if oral therapy cannot be tolerated. 

Cough In 5-20% of patients, ACE inhibitors induce a dry cough it usually is not dose-related, occurs more frequently in women than men, usually develops between 1 week and 6 months after initiation of therapy, and sometimes requires cessation of therapy. This adverse effect may be mediated by bradykinin, substance P, and/or prostaglandins. Thromboxane antagonism, aspirin, and iron supplementation reduce cough induced by ACE inhibitors. Once ACE inhibitors are stopped, the cough disappears, usually within 4 days. 

Anastrozole (Fig. 46.11) is a potent and highly selective, nonsteroidal aromatase inhibitor utilized in the treatment of advanced breast cancer that is hormone-responsive. It is considered to be second-line therapy (after tamoxifen) in the treatment of postmenopausal breast cancer. Anastrozole. a benzyltriazole derivative, competes with the natural substrate for binding to the active site of the aromatase. The mechanism of enzyme inhibition resides in the coordination of the triazole ring with the heme iron atom of the aromatase enzyme complex (161,162). This coordination ultimately prevents aromatization of androgens into estrogens and, therefore, deprives the tumor of estrogen. This effect is reversible. In the presence of anastrozole. estradiol levels are reduced to undetectable levels, with no adverse effects on levels of any other hormone, including cortisol and aldosterone. 

A number of adverse effects of excessive intakes of vitamin C have been reported, such as nausea abdominal cramps and diarrhea absorption of excessive amounts of food iron destruction of red blood cells increased mobilization of bone minerals interference with anticoagulant therapy formation of kidney and bladder stones the inactivation of vitamin B-12 a rise in plasma cholesterol and possible dependence upon large doses of vitamin C (small closes no longer meet nutritional needs). It is also noteworthy that undesirable side effects may be greater in certain physiological states (e.g. pregnancy). 

In a cost-utility multiple appraisal of deferasirox, deferoxamine, and deferiprone, it was concluded that in the short term there is little clinical difference between any of the three chelators in terms of removing iron from the blood and the liver, and that deferasirox may be cost-effective compared with deferoxamine but not compared with deferiprone [15 ]. The authors emphasized that the primary focus for future research should be on the longterm benefits of chelation therapy, including adverse reactions and adherence. 

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