Oral Iron Preparations

Oral iron preparations replace iron stores in iron deficiency anaemia. Ferrous salts are the first-line choice, because they are inexpensive and well absorbed. Absorption is limited by hepcidin, so lower or less frequent doses can give equal absorption with fewer gastrointestinal effects than multiple daily doses.

Mechanism. Ferrous iron is absorbed by divalent metal transporter 1 in duodenal enterocytes, exported by ferroportin and carried by transferrin to the marrow. Hepcidin rises for about 24 hours after each dose and blocks the next, which supports alternate-day dosing.

Pharmacokinetics. Absorption is 10 to 20% in deficiency and falls with higher doses and inflammation. Food, tea, coffee, calcium, phytates and proton pump inhibitors reduce absorption; vitamin C (250 mg) increases it.

Dosing.

• Adults: 65 to 200 mg elemental iron once daily, or on alternate days (for example, one 200 mg ferrous sulphate tablet every other morning). Maximum 200 mg elemental iron daily.
• Children: 3 mg/kg elemental iron daily (up to 6 mg/kg), maximum 200 mg; give a liquid preparation to young children.
• Pregnancy: 30 to 60 mg elemental iron daily for prevention; 100 to 200 mg daily for treatment.
• Duration: continue for 3 months after haemoglobin normalises to replenish stores.

Alternatives. Ferric maltol 30 mg twice daily (better tolerated, expensive); iron polysaccharide complexes and bisglycinate (fewer gastrointestinal effects, less evidence); carbonyl iron.

Administration. Take on an empty stomach, or with a small amount of food if not tolerated, with vitamin C or orange juice. Avoid tea, coffee, dairy and antacids for 2 hours. Separate from levothyroxine by 4 hours.

• First-line. Iron deficiency anaemia and iron deficiency without anaemia, in pregnancy and in children.
• Alternative. Alternate-day dosing or lower elemental doses when gastrointestinal effects occur; ferric maltol or switch to parenteral iron when intolerant.
• Specialist. Parenteral iron when oral iron fails, absorption is impaired (coeliac disease, bariatric surgery, inflammatory bowel disease), blood loss exceeds absorption, or the deficit is large.
• Emergency. None; transfusion for decompensation.

Assess response. Haemoglobin should rise by 10 g/L within 2 weeks and 20 g/L by 3 to 4 weeks. Failure: check adherence, ongoing blood loss, wrong diagnosis (thalassaemia trait, anaemia of chronic disease), malabsorption (coeliac disease, Helicobacter pylori, atrophic gastritis) and interacting drugs.

Contraindications. Haemochromatosis and iron overload; haemolytic anaemias without deficiency; repeated transfusion; intestinal obstruction, strictures or diverticular disease (relative); hypersensitivity.

Serious adverse effects. Nausea, abdominal pain, constipation or diarrhoea (30%); dark stools; tooth staining with liquids; iron poisoning in overdose (over 20 mg/kg elemental iron toxic; over 60 mg/kg severe and potentially fatal), causing vomiting, haematemesis, shock, metabolic acidosis and later liver failure; treat severe poisoning with deferoxamine 15 mg/kg/h intravenously and supportive care.

Major interactions. Reduced absorption of levothyroxine, quinolones, tetracyclines, penicillamine, bisphosphonates, levodopa, methyldopa and mycophenolate; absorption of iron reduced by proton pump inhibitors, H2 blockers, antacids, calcium and zinc; may cause false-positive stool tests.

Common prescribing errors.

• Dosing three times daily, which lowers absorption and tolerance.
• Prescribing the tablet strength instead of elemental iron.
• Stopping at haemoglobin normalisation.
• No investigation for blood loss.
• Children’s tablets left accessible.

Special groups.

• Pregnancy: prophylaxis 30 to 60 mg and treatment 100 to 200 mg elemental iron daily; if haemoglobin does not rise in 2 weeks switch to intravenous iron in the second or third trimester.
• Breastfeeding: compatible.
• Children: 3 mg/kg daily; liquid preparations; poisoning risk in toddlers.
• Older adults: constipation; alternate-day dosing.
• Kidney: oral iron often inadequate in dialysis patients.
• Liver: avoid in iron overload.
• East Africa: give with malaria diagnosis and treatment, and treat helminths; sickle cell disease does not need iron unless deficiency is proved.

Monitoring. Haemoglobin at 2 and 4 weeks; reticulocytes at 1 week; ferritin and transferrin saturation at 3 months after normal haemoglobin; compliance.

Referral and escalation. No haemoglobin rise by 4 weeks; suspected gastrointestinal bleeding or malignancy; iron overdose (immediate emergency care); bowel obstruction.

Comparison with alternative classes. Oral iron is cheap and effective in most patients, but slower and less tolerated than parenteral iron, which is preferred when absorption or adherence is poor or rapid repletion matters.