Ferrous sulfate

Ferrous sulfate is an oral iron supplement primarily used to treat and prevent iron deficiency anemia (IDA). As a ferrous (Fe²⁺) salt, it offers better gastrointestinal absorption than ferric forms and is commonly included in therapeutic regimens for anemia caused by chronic blood loss, poor dietary intake, malabsorption syndromes, or increased physiological needs such as in pregnancy.

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Pharmacological Classification

• Therapeutic Class: Hematinic, anti-anemic agent

• Pharmacologic Class: Oral iron supplement

• ATC Code: B03AA07

• Formulations:

  • Oral tablets (e.g. 200 mg, 325 mg)

  • Liquid suspensions/drops

  • Controlled-release tablets or capsules

Each 200 mg tablet of ferrous sulfate contains approximately 65 mg of elemental iron, although elemental iron content varies by brand and formulation.

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Mechanism of Action

Iron is vital for the synthesis of hemoglobin in red blood cells. In iron deficiency:

• Hemoglobin levels fall, reducing oxygen-carrying capacity.

• Ferrous sulfate restores iron stores in the bone marrow, liver, spleen, and muscle tissues.

• Once absorbed from the duodenum and upper jejunum, ferrous iron (Fe²⁺) is either used immediately for hemoglobin synthesis or stored as ferritin and hemosiderin.

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Therapeutic Indications

Approved Uses

• Treatment of iron deficiency anemia

• Prophylaxis of iron deficiency during:

  • Pregnancy

  • Lactation

  • Infancy/childhood growth spurts

  • Heavy menstrual bleeding

  • Chronic blood loss (e.g. peptic ulcers, IBD, haemorrhoids)

• Post-operative anemia correction (especially after bariatric surgery or major surgeries with blood loss)

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Dosage and Administration

Adults (Therapeutic Dose)

• 100–200 mg of elemental iron per day, usually in divided doses

  • For example: 1 tablet (65 mg elemental iron) 2–3 times daily

Prophylactic Dose (Adults)

• 30–60 mg of elemental iron daily

Children

• Based on age and weight:

  • Typically 3–6 mg/kg/day of elemental iron in divided doses

Pregnancy

• WHO recommends 30–60 mg elemental iron daily with 400 µg folic acid for prevention

• Therapeutic doses may reach 120 mg/day

Administration Tips

• Best taken on an empty stomach (1 hour before or 2 hours after food), but may be taken with meals if GI irritation occurs

• Avoid milk, tea, and antacids within 2 hours of dosing

• Vitamin C (ascorbic acid) enhances iron absorption

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Pharmacokinetics

• Absorption: Occurs mainly in the duodenum and proximal jejunum; only 10–15% of ingested iron is absorbed under normal conditions

• Peak plasma levels: Within 2–4 hours

• Bioavailability: Increased in iron-deficient states

• Transport: Bound to transferrin in blood

• Storage: As ferritin and hemosiderin in liver, spleen, and bone marrow

• Elimination: Very little iron is excreted; loss occurs mostly through sloughing of cells, sweat, and menstruation

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Contraindications

• Hemochromatosis

• Hemosiderosis

• Hemolytic anemia (iron is not beneficial in these conditions and may cause toxicity)

• Repeated blood transfusions without anemia

• Known hypersensitivity to ferrous salts

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Warnings and Precautions

• Use cautiously in patients with peptic ulcer disease, ulcerative colitis, or Crohn’s disease, as iron can worsen GI irritation

• Risk of iron overload with prolonged use, especially in patients with genetic iron metabolism disorders

• Accidental overdose in children is fatal – keep out of reach

• Prolonged therapy without confirming iron deficiency via lab tests is discouraged

• Black stools are a normal and harmless effect of iron therapy

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Adverse Effects

Very Common (>10%)

• Gastrointestinal disturbances:

  • Nausea

  • Constipation

  • Abdominal pain or cramps

  • Diarrhea

  • Metallic taste

  • Black or tarry stools (harmless discoloration)

Common (1–10%)

• Vomiting

• Flatulence

• Heartburn

• Esophagitis (if not swallowed properly)

Rare (<1%)

• Hypersensitivity reactions: rash, urticaria

• Anaphylaxis (mainly with parenteral forms, not oral ferrous sulfate)

• Teeth staining (with liquid formulations)

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Drug Interactions

Drugs that Decrease Iron Absorption

• Antacids, H2 blockers, PPIs: Reduce gastric acid required for iron solubilization

• Calcium supplements, magnesium salts: Compete for absorption

• Tetracyclines, fluoroquinolones, levothyroxine: Form insoluble complexes with iron (separate by 2–4 hours)

• Cholestyramine: May reduce iron absorption

Drugs Affected by Iron

• Levodopa, methyldopa, penicillamine: Reduced effectiveness due to chelation

• Bisphosphonates: Impaired absorption

• Thyroxine (levothyroxine): Absorption reduced; space administration by ≥4 hours

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Monitoring Parameters

• Hemoglobin and hematocrit

• Serum ferritin

• Transferrin saturation (TSAT)

• Total iron-binding capacity (TIBC)

• Reticulocyte count (early indicator of response, rises within 7–10 days)

• Adherence and tolerance (e.g., GI side effects)

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Duration of Therapy

• Hemoglobin usually rises by 1 g/dL every 2–3 weeks with adequate therapy

• Continue treatment for 3–6 months after normalization to replenish iron stores

• In severe deficiency or malabsorption, switch to parenteral iron

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Special Populations

Pregnancy

• Safe and widely used

• Routine supplementation advised, especially in low-resource settings

Breastfeeding

• Safe – iron content in breast milk is not significantly affected

Elderly

• More prone to constipation – stool softeners may be needed

Pediatrics

• High risk of accidental overdose – use child-resistant packaging and measure liquids carefully

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Patient Counseling Points

• Take on an empty stomach if possible for better absorption

• May cause black stools – this is harmless

• Constipation or stomach upset is common – taking with food may help, but reduces absorption

• Avoid taking with tea, coffee, dairy, calcium supplements, or antacids

• Use vitamin C-rich juice (like orange juice) to enhance absorption

• Do not crush or chew extended-release tablets

• Keep out of reach of children – iron overdose is fatal

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Comparison with Other Iron Supplements

Compared with ferric iron salts:

• Ferrous sulfate is better absorbed and more cost-effective

• Other oral ferrous preparations include:

  • Ferrous gluconate (less elemental iron, gentler on stomach)

  • Ferrous fumarate (higher elemental iron content per dose)

• Polysaccharide iron complex and heme iron polypeptide may be better tolerated but are costlier

• Parenteral iron (e.g., iron sucrose, ferric carboxymaltose) is reserved for those with malabsorption, intolerance, or severe anemia

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Brand Names

• Ferrograd®

• Feosol®

• Slow Fe®

• Fer-In-Sol®

• Ferrex®

• Generics: Ferrous sulfate 200 mg tablets, syrups, drops