Adverse GI effects are common after oral administration of iron salts. Adverse effects can diminish with use and may be reduced by taking iron immediately after meals for a few days, even though this can reduce total iron absorption. Smaller, more frequent doses also can help. The most common adverse GI effects are constipation, abdominal pain, dyspepsia, stool discoloration, nausea, and vomiting. Although infrequent, GI irritation may be severe enough to cause anorexia or diarrhea in some patients.[57505]

Liquid preparations of iron salts can produce tooth discoloration, a superficial and temporary staining of tooth enamel. Iron can bind to tooth surfaces on contact, or may collect in plaque or etchings on tooth surfaces, thereby causing discoloration. The iron solutions may impart a grey color to the affected teeth. Diluting oral iron liquids with water or fruit juice and drinking the solutions through a straw will help minimize contact of the solutions with the enamel of the teeth. Proper oral hygiene can prevent or remove staining, as can brushing with baking-soda. Iron tablets and capsules do not stain the teeth.[57506]

Solid oral iron dosage forms may produce local oral ulceration, or esophagitis or esophageal ulceration, respectively, if held within the mouth or lodged within the larynx or esophagus. Iron-induced esophagitis is characterized by sudden onset odynophagia, retrosternal pain, and dysphagia. Other severe complications such as esophageal stricture, bleeding, and perforation have been reported. Risk factors for iron-induced esophageal effects include taking the medication without water and at night. Symptoms usually resolve within days to weeks after stopping the medication. The accidental inhalation of solid iron dosage forms into the lungs has been reported to cause bronchial ulceration and necrosis. These rare events can produce significant morbidity.[57507] [57505]

Iron is not easily eliminated from the body and acute overdose may result in toxicity. Serum iron levels greater than 300 mcg/dl are potentially toxic. Elevated ferritin levels or transferrin oversaturation may also indicate iron poisoning. The clinical course of acute iron overdosage can be variable. Initial symptoms may include abdominal pain, nausea, vomiting, diarrhea, tarry stools, melena, hematemesis, hypotension, tachycardia, metabolic acidosis, hyperglycemia, dehydration, drowsiness, pallor, cyanosis, lassitude, seizures, shock and coma. Iron overload, which can occur after long-term use of iron, may cause exogenous hemosiderosis. Hemosiderosis is the result of deposition of hemosiderin, an iron-containing pigment, in the tissues of the liver and spleen. Hemosiderosis is rare with proper iron use; periodic monitoring of serum ferritin levels may be helpful in recognizing a progressive accumulation of iron resulting from impaired iron uptake from the reticuloendothelial system. Excessive chronic iron ingestion rarely, if ever, causes hemochromatosis unless a genetic predisposition to the disorder is also present (roughly <= 0.5% of the population). Hemochromatosis results in aberrations of iron metabolism and storage; iron accumulates in the body and excess iron deposition (hemosiderosis) occurs in the parenchymal tissues. With hemochromatosis, the liver becomes enlarged, and skin discoloration, specifically a bronze hue, occurs. Pancreatic dysfunction, diabetes mellitus, cardiac failure, liver failure and other tissue disorders may occur secondary to hemochromatosis.[57508]

Ferrous fumarate, an iron salt, has been associated with acute generalized exanthematous pustulosis (AGEP). The nonfollicular, pustular, erythematous rash starts suddenly, is associated with fever above 38 degrees C, and is distinct from pustular psoriasis, although biopsy results in each reveal spongiform subcorneal pustules. Drugs are the main cause of AGEP. A period of 2—3 weeks after an inciting drug exposure appears necessary for a first episode of AGEP. Unintentional reexposure may cause a second episode within 2 days. Clinical presentation is diverse with cutaneous lesions beyond erythema and pustules present in half of the cases. For example, bullous lesions, edema, purpura, pruritus, and mucosal erosions are possible. The mean duration of the pustules is 9.7 days followed by an annular desquamation, as long as the causative drug or factor is discontinued. The physiopathological mechanisms of AGEP have not been determined but the pathological criteria of edema, leukocytoclastic vasculitis, eosinophil exocytosis, and keratinocyte focal necrosis are distinctive. Pustule confluence or very small pustules may lead a clinician to make an incorrect diagnosis of TEN, of drug-induced erythroderma, or of staphylococcal scalded skin syndrome.[27736]

Iron salts are only useful for those anemia types where iron-deficiency co-exists. The type of anemia and the underlying cause or causes should be determined before starting therapy with iron. Unnecessary administration of iron salts may lead to iron overload and iron toxicity. Since anemia may be a result of a systemic disturbance, such as recurrent blood loss, the underlying cause(s) should be corrected, if possible. Exogenous Iron salts are only useful for those anemia types where iron-deficiency co-exists. The type of anemia and the underlying cause or causes should be determined before starting therapy with iron. Unnecessary administration of iron salts may lead to iron overload and iron toxicity. Since anemia may be a result of a systemic disturbance, such as recurrent blood loss, the underlying cause(s) should be corrected, if possible. Exogenous administration of iron salts will not alleviate hemolytic anemia and should only be administered to patients with hemolysis if an iron-deficiency is also present. Iron supplementation should be used cautiously in patients receiving blood transfusions because iron overload may occur.

Administration of iron salts to premature neonates can increase the risk of developing hemolytic anemia because these neonates may have a low vitamin E serum concentration. In general, iron supplementation should not begin until adequate vitamin E is supplied in the diet; human breast milk and modern infant formulas usually supply adequate dietary vitamin E.

Infants and children should receive iron salts only under the advice and supervision of a qualified health care professional. Accidental exposure to excessive amounts of iron-containing products (i.e., overdose) is the leading cause of fatal poisoning in children under the age of 6 years. Products that contain 30 milligrams (mg) or more of iron per dosage unit are packaged as individual unit-doses. This is to limit the number of pills or capsules a small child could accidentally consume once the package is opened. The FDA published the final rule on the packaging of iron in the January 15, 1997 Federal Register. Under U.S. Consumer Product Safety Commission regulations, most drugs and dietary supplements with more than 250 mg of iron per container must have child-resistant packages. Always store any iron-containing products out of the reach of children and pets. In the case of accidental exposure by ingestion, call a physician or poison control center immediately.

Those suffering from hereditary/genetic hemochromatosis or hemochromatosis due to secondary iron overload (e.g., as in iron-loading anemias such as thalassemia or sideroblastic anemia) need to avoid iron salts and other iron supplements. Hemochromatosis causes the body to lose its ability to regulate the amount of iron that is absorbed, leading to excess iron absorption and tissue storage. Massive deposition of iron (hemosiderosis) in parenchymal tissues in these conditions may damage the liver, heart, pancreas and other tissues. Porphyria cutanea tarda (PCT) is sometimes associated with parenchymal iron deposits; patients with PCT should avoid iron supplements unless prescribed by a physician. Excess iron supplementation in patients with PCT can contribute to hepatic uroporphinogen decarboxylase deficiency, but the mechanism is not clear. Some patients with chronic hepatic disease may have hemochromatosis or moderate iron overload in hepatic tissues. The liver is one of the main storage sites for iron, and advanced chronic liver disease may result in excess storage iron in the liver. Thus patients with hepatic disease should receive iron supplementation with caution and only under the direction of a health care prescriber.

Orally administered iron salts may have a corrosive effect that may exacerbate the symptoms associated with certain GI disease states such as peptic ulcer disease or inflammatory bowel disease (e.g., ulcerative colitis). Patients with dysphagia have, on rare occasions, developed oral or esophageal ulcerations from difficulty in swallowing solid oral iron dosage forms. Iron salts may produce constipation and should be used with care in patients with GI obstruction or ileus. Iron products may cause false-positive results on stool guaiac tests for blood.

When ingested in amounts according to the recommended daily allowances (RDA), iron salts are considered safe for use during pregnancy. Routine iron supplementation during pregnancy appears to prevent low maternal hemoglobin at birth and in the immediate postpartum period. The effect of routine iron supplementation on fetal or maternal outcomes is not clear, but is thought to be beneficial. Pregnant women should supplement iron salts during pregnancy only when advised to do so by a qualified health care professional.[52044] [62528]

Use of iron supplements within the recommended daily dietary intake for lactating women is generally recognized as safe.[49822] While iron is excreted into breast-milk, the iron content of breast milk is not readily affected by the iron content of the maternal diet or the maternal serum iron level.[49626] Therefore, the use of iron salts, under the direction of a health care prescriber, is compatible with breast-feeding if the lactating mother needs treatment for iron deficiency. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

Some iron products contain sulfites and should be used with caution in patients with a known sulfite hypersensitivity. Although the overall prevalence of sulfite hypersensitivity is low, it is seen more frequently in asthmatics or in atopic non-asthmatic persons.