Should oral iron tablets be started during an acute upper gastrointestinal bleed, or only after hemostasis and when the patient can tolerate oral intake?

Oral Iron in Acute Upper GI Bleed: Timing and Safety

Oral iron tablets should be started immediately after hemostasis is achieved and the patient can tolerate oral intake, but not during active bleeding. 1, 2

Contraindications During Active Bleeding

• Do not administer oral iron during active upper gastrointestinal hemorrhage because the priority is hemodynamic resuscitation, endoscopic hemostasis, and high-dose proton pump inhibitor therapy. 3
• Oral iron can interfere with endoscopic visualization if colonoscopy or repeat endoscopy is imminent, and iron replacement therapy should be deferred only in this specific circumstance. 1, 2
• During the acute bleeding phase, management focuses on hemodynamic stabilization, early endoscopy (within 24 hours), endoscopic hemostasis for high-risk lesions (Forrest Ia, Ib, IIa), and intravenous PPI therapy (80 mg bolus then 8 mg/hour infusion for 72 hours). 3

When to Initiate Oral Iron

Begin oral iron supplementation as soon as the bleeding source is controlled and the patient can safely swallow, typically within 24–72 hours post-hemostasis. 1, 2

• Iron replacement therapy should not be deferred while awaiting further investigations for iron deficiency anemia unless endoscopy is scheduled within days. 1, 2
• The British Society of Gastroenterology explicitly recommends that iron replacement should begin promptly after hemostasis, as delaying treatment worsens anemia and prolongs recovery. 1, 2

Recommended Oral Iron Regimen Post-Hemostasis

• Prescribe ferrous sulfate 200 mg (65 mg elemental iron) once daily on an empty stomach as first-line therapy. 1, 2, 4
• Once-daily dosing is superior to multiple daily doses because hepcidin elevation persists for 48 hours after iron intake, blocking subsequent absorption and increasing gastrointestinal side effects without improving efficacy. 1, 2, 4
• Add vitamin C 500 mg with each iron dose to enhance absorption, especially critical when transferrin saturation is severely low after acute blood loss. 1, 2, 4
• Alternative formulations (ferrous fumarate or ferrous gluconate) are equally effective if ferrous sulfate is not tolerated. 1, 2, 4

Monitoring and Expected Response

• Check hemoglobin at 2–4 weeks; expect a rise of approximately 2 g/dL (20 g/L) if oral therapy is effective. 1, 2, 4
• Failure to achieve at least a 10 g/L rise by 2 weeks strongly predicts treatment failure (sensitivity 90.1%, specificity 79.3%) and warrants reassessment for ongoing blood loss, malabsorption, or need for intravenous iron. 4
• Continue oral iron for 3 months after hemoglobin normalizes to fully replenish iron stores; total treatment duration is typically 6–7 months. 1, 2, 4

When to Use Intravenous Iron Instead

Switch to intravenous iron if oral therapy fails or specific high-risk conditions are present:

• Intolerance to at least two different oral iron preparations despite trying ferrous sulfate, ferrous fumarate, and ferrous gluconate. 1, 2
• Ferritin levels fail to improve after 4 weeks of compliant oral therapy. 1, 2
• Active inflammatory bowel disease with hemoglobin <10 g/dL, because inflammation-induced hepcidin severely impairs oral iron absorption. 1, 2
• Post-bariatric surgery patients with disrupted duodenal iron absorption. 1, 2
• Ongoing gastrointestinal blood loss exceeding oral replacement capacity. 1, 2
• Severe symptomatic anemia requiring rapid correction (hemoglobin <7 g/dL or hemodynamic instability). 2

Preferred IV Iron Formulations

• Choose formulations that can replace iron deficits in 1–2 infusions: ferric carboxymaltose (750–1000 mg per 15-minute infusion) or ferric derisomaltose (1000 mg single infusion). 2, 5
• All IV iron products have similar safety profiles; true anaphylaxis is rare (0.6–0.7%), and most reactions are complement-activation pseudo-allergies that respond to slower infusion rates. 2, 6
• Administer IV iron only in facilities equipped for resuscitation. 2, 6

Real-World Evidence Gap

Despite clear guidelines, iron deficiency after acute GI bleeding is severely undertreated in clinical practice. A 2025 study of 337 patients hospitalized with severe GI bleeding found that iron studies were ordered in only 50% of cases, iron deficiency was diagnosed in 75% when tested, yet only 7.1% received IV iron and 26.7% received oral iron. 7 This represents a critical quality-of-care gap, as untreated iron deficiency after GI bleeding is associated with poor clinical outcomes, especially in patients with severe comorbidities. 7

Critical Pitfalls to Avoid

• Do not prescribe multiple daily doses of oral iron; this increases side effects without improving efficacy due to hepcidin-mediated absorption blockade. 1, 2, 4
• Do not stop iron therapy when hemoglobin normalizes; continue for 3 additional months to replenish stores. 1, 2, 4
• Do not persist with oral iron beyond 4 weeks without a hemoglobin rise; reassess for ongoing blood loss, malabsorption, or need for IV iron. 1, 2, 4
• Do not overlook vitamin C supplementation when oral iron response is suboptimal. 1, 2, 4
• Do not fail to investigate and treat the underlying bleeding source while providing iron supplementation. 1, 2
• Do not use oral iron during active bleeding or immediately before scheduled endoscopy, as it can interfere with visualization. 1, 2