IRON SALTS
General Monograph
Anemia Therapy
Pharmacology: Iron is an important component of a number of enzymes necessary for energy transfer. It is also present in hemoglobin and myoglobin and is important in the metabolism of catecholamines and the functioning of neutrophils.
Administration of iron preparations corrects erythropoietic abnormalities which are due to deficiency of iron. Iron does not stimulate erythropoiesis nor does it correct hemoglobin disturbances not caused by iron deficiency. In fact, it may cause iron storage disease or iron toxicity when used in these conditions.
Administration of iron also relieves other symptoms of iron deficiency such as soreness of the tongue, dysphagia, dystrophy of the nails and skin, and fissuring of the angles of the lips.
Pharmacokinetics: Absorption of iron is influenced by many factors including the form in which it is administered, the dose, the status of the patient’s iron stores, the degree of erythropoiesis, and the patient’s diet. Absorption will be increased in iron deficient individuals. Ferrous iron passes through gastrointestinal mucosal cells directly into the blood and is immediately bound to transferrin which transports iron to the bone marrow where it is incorporated into hemoglobin. Maximal absorption takes place in the duodenum and proximal jejunum; therefore, iron may not be as well absorbed from slow-release and delayed-release preparations which may bypass the site of optimal absorption.
The body has no physiological route for the excretion of excess iron. Most of the iron liberated by destruction of hemoglobin is conserved and reused. Normal daily excretion of iron from cell desquamation varies from 0.5 to 2 mg. The average monthly loss of iron in normal menstruation is 12 to 30 mg.
Frequent blood donors, pregnant women, burn victims, individuals on hemodialysis, or with intestinal diseases (celiac, Crohn’s, sprue, inflammatory bowel disease) and premature infants may require prophylactic therapy.
In its 1991 policy statement, the The Canadian Paediatric Society states that term infants who are not breast-fed should receive iron-fortified formula from birth, and that term breast-fed infants do not require supplemental iron until after 6 months of age.
Indications: Prevention and treatment of iron deficiency anemias.
Contraindications: Hemosiderosis, hemochromatosis. Iron compounds are also contraindicated in the treatment of anemia other than iron deficiency. Administration of iron to premature infants with vitamin E deficiency may precipitate red cell hemolysis. Therefore, vitamin E deficiency should also be corrected if possible.
Because of the risk of iron overload, oral and parenteral iron therapy should not be used concomitantly.
Precautions: Prolonged administration of iron should be avoided except in patients with continued bleeding, malabsorption syndromes that benefit from additional iron therapy or repeated pregnancies.
Orally administered iron salts may not be well absorbed in patients with steatorrhea and those who have had a partial gastrectomy.
Liquid iron preparations may stain the teeth on continued use. Stains may be prevented to a large extent by taking the dose through a straw, first mixing it with water or fruit juice, and by following the dose with a drink of plain water or juice. Brushing the teeth with sodium bicarbonate or hydrogen peroxide 3% will usually remove existing stains.
Drug Interactions : Iron may decrease the absorption of the following drugs: etidronate, tetracycline, penicillamine, quinolone antibiotics, levodopa, methyldopa and levothyroxine. It is recommended that administration of these drugs with iron be separated by at least 2 hours. Patients should be monitored for inadequate clinical response and switched to alternative therapy if necessary.
Administration of iron and either vitamin E or chloramphenicol may impair the hematological response to iron.
Concomitant administration of antacids (containing aluminum and magnesium salts or sodium bicarbonate or calcium carbonate) or cholestyramine may impair the absorption of iron.
Drug-Laboratory Test Interactions : Because iron preparations can color the feces black, large amounts may interfere with the guaiac test for occult blood in stool.
Pregnancy: No adverse effects have been reported with intake of normal daily requirements.
Lactation: At therapeutic doses, amount excreted in breast milk is not significant to affect infant.
Children: Deaths have occurred in children from as little as 400 mg of elemental iron. Severe reactions, including fatalities, have resulted. Patients should be warned about the extreme danger to children of accidental iron poisoning.
In infants, large chronic doses of iron may interfere with the assimilation of phosphorus and cause severe rickets.
Adverse Effects: Oral ingestion of iron preparations may be associated with gastrointestinal discomfort (such as nausea) or epigastric pain, dose related bowel effects (such as constipation or diarrhea) and dark stools. Untoward effects usually subside with continuation of therapy. Other measures may be helpful such as taking doses with or after meals, or initiating therapy at lower doses and gradually increasing to the therapeutic dose.
Liquid iron preparations may stain teeth (see Precautions).
tag_OverdoseOverdose: Iron poisoning is rare in adults, but serious acute toxicity may occur in children. The estimated lethal dose of iron is 200 to 300 mg/kg. Toxicity following ingestion of greater than 60 mg/kg is likely. However, toxicity following doses of 20 to 60 mg/kg has been observed.Symptoms: Acute poisoning with iron has 4 distinct phases. Signs and symptoms may occur within about 30 minutes or may be delayed for several hours. The first phase, which may last up to 6 hours, includes symptoms such as epigastric pain, nausea, vomiting, diarrhea, melena and hematemesis that may be associated with drowsiness, pallor, cyanosis, lassitude, shock, coagulopathy, acidosis and coma. Following this first phase, there may be a transient period of apparent recovery which may last up to 24 hours. The third phase, occurring from 4 to 48 hours post ingestion, may be manifested by metabolic acidosis, hypotension, convulsions, fever, hepatic dysfunction or necrosis, renal failure, and later progress to circulatory collapse, coma and death. Possible intestinal scarring and obstruction may occur 2 to 4 weeks post-ingestion as part of the fourth phase.
Treatment: Obtain CBC, blood glucose, electrolytes and serum iron level. In severe overdose also obtain PT, PTT and liver function tests. Remove as much iron as possible from the gastrointestinal tract, using ipecac syrup or gastric lavage. Use tepid water. Administration of magnesium citrate cathartic or surgical removal of iron tablets may be required if other methods are unsuccessful. Maintain fluid and electrolyte balance.
Parenteral deferoxamine may be used when serum iron level is >63 µmol/L. Peak level generally occurs 3 to 6 hours after ingestion; however, it may be longer after ingestion of enteric coated or sustained release preparations. Patients who develop a WBC>15´10L or blood glucose >8.3 mmol/L are more likely to have toxic iron levels and should be admitted to hospital and administered deferoxamine if they develop symptoms. Hemodialysis is of little value in cases of iron poisoning.
Dosage: In preventing iron deficiency, adequate dietary intake is preferred over supplementation whenever possible. For a listing of food sources of iron, see Mineral Food Sources in the Clin-Info section.
The recommended daily intake of iron to prevent deficiency is 0.3 mg in infants less than 4 months and 6 to 8 mg in older infants and children. Adolescents and adults should receive 8 to 13 mg daily. An additional 5 mg/day is recommended in the second trimester of pregnancy with an additional 10 mg/day in the third trimester. Additional iron is not usually required during the first trimester or lactation. For a complete listing of the daily requirements of iron and other vitamins and minerals, see Recommended Nutrient Intake in the Clin-Info section.
Calculation of dosage for iron preparations should always be in terms of the elemental iron to be administered rather than in terms of the iron salt.
For iron deficient adults, 50 to 100 mg of elemental iron given orally 3 times daily is usually adequate. Absorption is optimal in the fasting state. To lessen gastrointestinal intolerance, lower doses may be administered initially, and the medication may be given with or after meals. After 4 or 5 days the dose may be gradually increased. After the hemoglobin returns to normal, oral therapy should be continued for 3 to 6 months to replenish stores.
Iron deficient children may receive 4 to 6 mg/kg elemental iron daily in 3 divided doses.
IRON SALTS General Monograph Anemia Therapy
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