AGENTS USED FOR IRON DEFICIENCY ANEMIA

Although most people get all of the iron they need through diet, in some situations diet alone may not be adequate. The iron preparations that are available include ferrous fumarate (Feostat), ferrous gluconate (Fergon), ferrous sulfate (Feosol), ferrous sulfate exsiccated (Feratab, Slow FE), ferumoxytol (Feraheme), iron dextran (InFeD), iron sucrose (Venofer), and sodium ferric gluconate complex (Ferrlecit).

Therapeutic Actions and Indications They are indicated for the treatment of iron deficiency anemias and may also be used as adjunctive therapy in patients receiving an erythropoiesis-stimulating drug.

Pharmacokinetics Ferrous fumarate, ferrous gluconate, ferrous sulfate, and ferrous sulfate exsiccated are available for oral administration. Iron dextran is a parenteral form of iron given by the Z-track method, which may be used if an oral form cannot be given or cannot be tolerated. Patients with severe GI absorption problems may require this form of iron.

Patients should be switched to the oral form if at all possible because of the pain associated with intramuscular (IM)administration of iron. Iron sucrose, ferumoxytol and sodium ferric gluconate complex are given intravenously specifically for patients who are undergoing chronic hemodialysis or who are in renal failure and not on dialysis but are receiving supplemental erythropoietin therapy.

Iron is primarily absorbed from the small intestine by an active transport system. It is transported in the blood, bound to transferrin. Small amounts are lost daily in the sweat, urine, sloughing of skin and mucosal cells, and sloughing of intestinal cells, as well as in the menstrual flow of women. Most of the oral drug that is taken is lost in the feces, but slowly some of the metal is absorbed into the intestine and transported to the bone marrow. It can take 2 to 3 weeks to see improvement and up to 6 to 10 months for a return to a stable iron level once a deficiency exists. It is used during pregnancy and lactation to help the mother meet the increased demands for iron that occur at those times.

Contraindications and Cautions These drugs are contraindicated for patients with known allergy to any of these preparations because severe hypersensitivity reactions have been associated with the parenteral form of iron. They also are contraindicated in the following conditions: hemochromatosis (excessive iron);hemolytic anemias, which may increase serum iron levels and cause toxicity; normal iron balance because the drug will not be absorbed and will just pass through the body;and peptic ulcer, colitis, or regional enteritis because the drug can be directly irritating to these tissues and can cause exacerbation of the diseases.

Adverse Effects The most common adverse effects associated with oral iron are related to direct GI irritation; these include GI upset, anorexia, nausea, vomiting, diarrhea, dark stools,and constipation. With increasing serum levels, iron can be directly toxic to the CNS, causing coma and even death.

Parenteral iron is associated with severe anaphylactic reactions, local irritation,staining of the tissues, and phlebitis. Ferumoxytol is a supermagnetic iron oxide that can alter MRI images and interpretation for up to 3 months after administration;patients should be aware that they have been given this drug and cautioned to report it before undergoing any medical testing.

Chelating Agents Heavy metals, including iron, lead, arsenic, mercury,copper, and gold, can cause toxicity in the body by their ability to tie up chemicals in living tissues that need to be free in order for the cell to function normally. When these vital substances (thiols, sulfurs, carboxyls, and phosphoryls)are bound to the metal, certain cellular enzyme systems become deactivated, resulting in failure of cellular function and eventual cell death. Drugs that have been developed to counteract metal toxicity are called chelating agents (from the Greek word for “claw”).

Chelating agents grasp and hold a toxic metal so that it can be carried out of the body before it has time to harm the tissues. The chelating agent binds the molecules of the metal, preventing it from damaging the cells within the body. The complex that is formed by the chelating agent and the metal is nontoxic and is excreted by the kidneys.

Clinically Important Drug–Drug Interactions Iron absorption decreases if iron preparations are taken with antacids, tetracyclines, or cimetidine; if these drugs must be used, they should be spaced at least 2 hours apart. Anti-infective response to ciprofloxacin, norfl oxacin,or ofl oxacin can decrease if these drugs are taken with iron because of a decrease in absorption; they also should be administered at least 2 hours apart. Increased iron levels occur if iron preparations are taken with chloramphenicol; patients receiving this combination should be monitored closely for any sign of iron toxicity. The effects of levodopa may decrease if it is taken with iron preparations; patients receiving both of these drugs should take them at least 2 hours apart.

Clinically Important Drug–Food Interactions Iron is not absorbed if taken with antacids, eggs, milk, coffee, or tea. These substances should not be administered concurrently. Acidic liquids may enhance the absorption of iron and should be not be given concurrently.