Ferrous Sulfate

Ferrous sulfate is an oral ferrous iron salt and the most widely used first-line treatment for iron deficiency and iron deficiency anaemia. Dried ferrous sulfate 200 mg and ferrous sulfate 325 mg tablets each supply about 65 mg of elemental iron, and every dose is written as elemental iron to prevent salt-weight errors.

Classification. Haematinic; oral iron replacement.

Mechanism. Supplies iron for haem and iron-sulphur enzyme synthesis and for erythroid expansion. Iron is reduced to the ferrous state, taken up at the duodenal enterocyte by the divalent metal transporter and exported by ferroportin, which hepcidin blocks.

Pharmacokinetics. Absorption is about 10 to 20%, higher in deficiency and lower when hepcidin is raised by inflammation or by a dose taken in the previous 24 hours. Iron is carried on transferrin and stored as ferritin. There is no regulated excretion; obligatory loss is about 1 to 2 mg daily through shed cells.

Iron deficiency anaemia, adults.

• Dose: 65 mg elemental iron orally once daily, or on alternate days if tolerance is poor.
• Frequency and titration: increase to twice or three times daily only if tolerated and response is slow; larger daily doses add adverse effects without proportionate absorption.
• Maximum: 200 mg elemental iron daily (three 65 mg tablets). Loading dose: none. Maintenance: the same dose.
• Duration: until haemoglobin is normal, then a further 3 months to replenish stores.
• Expected response: haemoglobin rise of about 10 g/L within 2 to 4 weeks.

Pregnancy.

• Prophylaxis: 30 to 60 mg elemental iron orally once daily, usually with folic acid 400 µg.
• Treatment of anaemia: 65 mg orally one to three times daily (maximum 200 mg daily) until haemoglobin is normal, then continue through delivery and for 3 months postpartum.

Children.

• Treatment: 3 mg/kg of elemental iron daily orally in one or two doses, up to 6 mg/kg daily; maximum 200 mg daily; for 3 months.
• Prophylaxis: 1 to 2 mg/kg daily, not exceeding the treatment maximum.
• Preterm infants: 2 to 3 mg/kg daily from about 2 to 6 weeks of age, directed by the neonatal team.

Adjustments. Kidney: no adjustment, but oral iron is often ineffective in advanced chronic kidney disease and in haemodialysis, where intravenous iron is preferred. Liver: no adjustment; avoid in iron overload. Age: older adults tolerate once-daily or alternate-day dosing best.

Contraindications. Haemochromatosis, haemosiderosis and other iron overload, anaemias not due to iron deficiency (thalassaemia trait, anaemia of chronic disease alone), and hypersensitivity. Use caution in active inflammatory bowel disease, strictures and diverticular disease.

Adverse effects. Common: nausea, epigastric pain, constipation, diarrhoea, metallic taste and black stools, which are not melaena. Serious: oesophageal or gastric mucosal injury from tablets that lodge, and acute poisoning.

Boxed-warning-level risk. Accidental iron ingestion is a leading cause of fatal poisoning in children under 6 years; tablets must be stored out of reach.

Interactions. Reduced iron absorption with proton pump inhibitors, H2 antagonists, antacids, calcium, tea, coffee, milk and phytate-rich foods. Iron reduces absorption of levothyroxine, ciprofloxacin and other quinolones, tetracyclines, levodopa, methyldopa, penicillamine, bisphosphonates and mycophenolate. Dolutegravir absorption falls with iron unless both are taken together with food; otherwise give dolutegravir 2 hours before or 6 hours after iron.

Pregnancy and breastfeeding. Used throughout pregnancy and compatible with breastfeeding.

Regional points. In East Africa, iron deficiency is frequently driven by hookworm, schistosomiasis and menstrual or obstetric blood loss, so treat the cause. In children in malaria-endemic areas, give iron only where malaria prevention and treatment are available.

Common errors. Prescribing in mg of salt rather than elemental iron; not searching for the cause in men and postmenopausal women; continuing iron once ferritin is replete.

Administration. Take on an empty stomach, 30 to 60 minutes before food, with water or fruit juice; take with food if intolerance prevents adherence. Morning dosing on alternate days improves fractional absorption.

Baseline. Full blood count, reticulocytes, ferritin, transferrin saturation and C-reactive protein; look for blood loss and malabsorption.

Monitoring. Haemoglobin at 2 to 4 weeks, then at 3 months. Ferritin under 30 µg/L confirms deficiency, or under 100 µg/L with inflammation or chronic kidney disease. Stop when ferritin is replete and haemoglobin is normal.

Referral and escalation. Move to intravenous iron if there is intolerance, no haemoglobin rise after 4 weeks of confirmed adherence, malabsorption, ongoing loss, chronic kidney disease, heart failure or late pregnancy. Acute ingestion above 20 mg/kg elemental iron needs observation; above 60 mg/kg or any systemic symptoms needs emergency chelation assessment.