Ferrous sulfate, - Drug Monograph

Ferrous Sulfate - Drug Monograph

Introduction

Ferrous sulfate is an iron salt preparation widely used as an oral iron supplement and therapeutic agent for the treatment of iron deficiency and iron deficiency anemia. As one of the most commonly prescribed and readily available forms of iron, it plays a crucial role in managing conditions characterized by inadequate iron stores. Ferrous sulfate remains the gold standard against which other iron preparations are compared due to its well-established efficacy, safety profile, and cost-effectiveness.

Mechanism of Action

Ferrous sulfate provides elemental iron, which is essential for hemoglobin synthesis, oxygen transport, and various cellular metabolic processes. After oral administration, ferrous iron (Fe²⁺) is absorbed in the duodenum and proximal jejunum via active transport mechanisms. Once absorbed, iron is incorporated into hemoglobin in developing erythrocytes, stored as ferritin or hemosiderin, or utilized in various iron-containing enzymes and cytochromes involved in cellular respiration and energy production.

Indications

• Treatment of iron deficiency anemia
• Prophylaxis of iron deficiency in high-risk populations (pregnancy, chronic blood loss, malnutrition)
• Iron supplementation in patients with increased requirements (rapid growth periods, blood donors)
• Adjunctive therapy in patients receiving erythropoietin-stimulating agents

Dosage and Administration

• Treatment of iron deficiency: 325 mg (65 mg elemental iron) orally 2-3 times daily
• Prophylaxis: 325 mg orally once daily

• Treatment: 3-6 mg elemental iron/kg/day in divided doses
• Prophylaxis: 1-2 mg elemental iron/kg/day

• Renal impairment: No dosage adjustment required
• Hepatic impairment: Use with caution; monitor iron levels
• Pregnancy: 30-60 mg elemental iron daily for prophylaxis; higher doses for treatment
• Geriatric: Standard adult dosing; consider reduced doses in frail elderly

• Take on an empty stomach 1 hour before or 2 hours after meals for maximum absorption
• If gastrointestinal upset occurs, administer with food (reduces absorption by 40-50%)
• Avoid concomitant administration with antacids, calcium supplements, or dairy products
• Tablets may be crushed and mixed with food or liquid for patients with swallowing difficulties

Pharmacokinetics

• Primarily absorbed in duodenum and proximal jejunum
• Bioavailability: 5-35% depending on iron stores and concomitant factors
• Absorption enhanced by acidic environment, ascorbic acid, empty stomach
• Absorption decreased by food, antacids, phytates, polyphenols, calcium supplements

• Bound to transferrin in circulation
• Crosses placenta and enters breast milk
• Volume of distribution: approximately 3-4 L

• Iron is incorporated into hemoglobin or stored as ferritin/hemosiderin
• Not metabolized by hepatic enzymes

• Minimal renal excretion
• Primarily eliminated in feces via sloughing of intestinal mucosal cells
• Small amounts lost in sweat, skin cells, and urine
• Half-life: 6 hours (circulating iron)

Contraindications

• Hemochromatosis, hemosiderosis, or other iron overload disorders
• History of allergic reaction to ferrous sulfate or any component of the formulation
• Hemolytic anemia not associated with iron deficiency
• Repeated blood transfusions
• Certain types of anemia not due to iron deficiency (megaloblastic anemia, aplastic anemia)

Warnings and Precautions

• Accidental overdose: Iron poisoning is a leading cause of fatal poisoning in children under 6 years. Keep out of reach of children.
• GI effects: May cause constipation, diarrhea, nausea, vomiting, abdominal pain, and dark stools
• Iron overload: Prolonged excessive use may cause hemosiderosis and tissue damage
• Peptic ulcer disease: Use with caution in patients with active disease or inflammatory bowel disease
• Vitamin B12 deficiency: Iron therapy may unmask or exacerbate symptoms of vitamin B12 deficiency
• Parenteral iron: Consider in patients who cannot tolerate oral iron or have malabsorption syndromes

Drug Interactions

• Antacids, H2-receptor antagonists, proton pump inhibitors: Decreased iron absorption due to increased gastric pH
• Tetracyclines, quinolones: Form insoluble complexes reducing absorption of both agents (separate administration by 2-4 hours)
• Levothyroxine: Decreased absorption; separate administration by at least 4 hours
• Bisphosphonates: Reduced absorption of both agents; separate administration by at least 2 hours
• Cholestyramine, colestipol: Decreased iron absorption
• Vitamin C: Enhances iron absorption
• Chloramphenicol: May delay iron clearance and erythroid response

Adverse Effects

• Gastrointestinal: nausea, epigastric pain, constipation, diarrhea, dark stools
• Metallic taste

• Heartburn
• Temporary tooth staining (liquid formulations)

• Allergic reactions
• Urticaria
• Anaphylaxis (very rare)

• Acute: vomiting, abdominal pain, bloody diarrhea, metabolic acidosis, shock, hepatic necrosis
• Chronic: hemosiderosis, organ damage

Monitoring Parameters

• Hemoglobin/hematocrit at 2-4 week intervals until normalized, then every 3-6 months
• Reticulocyte count (expected increase within 5-10 days)
• Iron studies (serum iron, TIBC, ferritin) to assess iron stores
• Complete blood count with indices
• Gastrointestinal tolerance
• Signs of iron overload in long-term therapy
• Adherence assessment

Patient Education

• Take on empty stomach for best absorption, but with food if GI upset occurs
• Expect darkening of stools (harmless and expected)
• Do not exceed recommended dosage
• Keep out of reach of children (risk of fatal poisoning)
• Separate from antacids, calcium supplements, dairy products, tea, or coffee by 2 hours
• Liquid preparations may stain teeth; use straw and rinse mouth after administration
• Report severe constipation, abdominal pain, or signs of allergic reaction
• Store in original container away from moisture and light
• Complete full course of therapy even after feeling better

References

1. Lopez A, Cacoub P, Macdougall IC, et al. Iron deficiency anaemia. Lancet. 2016;387(10021):907-916. 2. Camaschella C. Iron-deficiency anemia. N Engl J Med. 2015;372(19):1832-1843. 3. Goddard AF, James MW, McIntyre AS, et al. Guidelines for the management of iron deficiency anaemia. Gut. 2011;60(10):1309-1316. 4. Pasricha SR, Drakesmith H, Black J, et al. Control of iron deficiency anemia in low- and middle-income countries. Blood. 2013;121(14):2607-2617. 5. Tolkien Z, Stecher L, Mander AP, et al. Ferrous sulfate supplementation causes significant gastrointestinal side-effects in adults: a systematic review and meta-analysis. PLoS One. 2015;10(2):e0117383. 6. FDA Drug Safety Communication: Boxed Warning and New Recommendations to Reduce Risk of Iron Overload. U.S. Food and Drug Administration. 2017. 7. Auerbach M, Adamson JW. How we diagnose and treat iron deficiency anemia. Am J Hematol. 2016;91(1):31-38. 8. Pavord S, Daru J, Prasannan N, et al. UK guidelines on the management of iron deficiency in pregnancy. Br J Haematol. 2020;188(6):819-830.