Ferrous Fumarate

Ferrous fumarate is an oral ferrous iron salt used for the prevention and treatment of iron deficiency. It contains about 33% elemental iron by weight, so a 200 mg tablet supplies about 65 mg of elemental iron; products vary, and all doses here are written as elemental iron.

Classification. Haematinic; oral iron replacement.

Mechanism. Supplies iron for haem synthesis and erythropoiesis. Uptake is through the divalent metal transporter after reduction to the ferrous state, with export by ferroportin under hepcidin control.

Pharmacokinetics. Absorption is about 10 to 20%, falling when hepcidin is raised. Iron is bound to transferrin and stored as ferritin; there is no regulated excretion.

Iron deficiency anaemia, adults.

• Dose: 65 mg elemental iron orally once daily or on alternate days; may be increased to twice or three times daily if tolerated.
• Maximum: 200 mg elemental iron daily. Loading dose: none. Maintenance: the same dose.
• Duration: until haemoglobin is normal, then 3 months more to replenish stores.

Pregnancy.

• Prophylaxis: 30 to 60 mg elemental iron daily, usually with folic acid 400 µg.
• Treatment of anaemia: 65 mg one to three times daily, maximum 200 mg daily.

Children.

• Treatment: 3 mg/kg of elemental iron daily 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. Syrups are common; dose by elemental iron content, which differs between products.

Adjustments. Kidney: no adjustment, but oral absorption is poor in advanced kidney disease. Liver: none; avoid in iron overload.

Contraindications. Iron overload states, haemochromatosis, non-iron-deficiency anaemias and hypersensitivity. Caution in active inflammatory bowel disease and bowel strictures.

Adverse effects. Nausea, abdominal pain, constipation, diarrhoea and black stools. Some patients tolerate fumarate better than sulfate, though evidence for a real difference is weak. Serious: mucosal injury and poisoning.

Boxed-warning-level risk. Accidental overdose is a leading cause of fatal poisoning in young children.

Interactions. Absorption falls with proton pump inhibitors, antacids, calcium, tea and dairy. Iron lowers absorption of levothyroxine, quinolones, tetracyclines, levodopa, methyldopa, penicillamine, bisphosphonates and mycophenolate. Separate by 2 to 4 hours. Dolutegravir is taken 2 hours before or 6 hours after iron, or together with a meal.

Pregnancy and breastfeeding. Suitable in both.

Regional points. Hookworm and schistosomiasis commonly contribute to deficiency in East Africa; treat the cause and review malaria cover in children.

Common errors. Confusing the 200 mg salt weight with elemental iron; failing to find the source of loss.

Administration. Take before food with water or fruit juice, or with food if not tolerated. Alternate-day dosing may improve absorption and tolerability.

Baseline. Full blood count, ferritin, transferrin saturation and C-reactive protein.

Monitoring. Haemoglobin rise of about 10 g/L in 2 to 4 weeks; recheck at 3 months; ferritin to confirm replete stores, with deficiency defined as under 30 µg/L, or under 100 µg/L with inflammation.

Referral and escalation. Switch to intravenous iron for intolerance, non-response after 4 weeks of adherence, malabsorption, ongoing loss or chronic kidney disease. Ingestion above 20 mg/kg elemental iron requires observation and above 60 mg/kg requires emergency treatment.