What is the recommended regimen for elemental iron supplementation in patients at risk of iron deficiency anemia, particularly pregnant women, individuals with a history of gastrointestinal bleeding, or those with chronic kidney disease?

Elemental Iron Supplementation Regimens

For most patients at risk of iron deficiency anemia, start with oral elemental iron 60-120 mg daily taken as a single morning dose on alternate days to maximize absorption and minimize side effects, with specific adjustments based on patient population and clinical context. 1, 2

General Adult Population (Non-Pregnant)

Oral iron is first-line therapy for most patients with iron deficiency anemia, as it is effective, available, inexpensive, and safe. 1

Dosing Strategy

• Standard dose: 100-200 mg elemental iron daily, though recent evidence suggests lower or alternate-day dosing may be superior 1, 3
• Optimal regimen: 60-120 mg elemental iron given as a single morning dose on alternate days rather than daily 2
  • Doses ≥60 mg stimulate hepcidin elevation that persists 24 hours, reducing absorption of subsequent doses 2
  • Alternate-day dosing maximizes fractional iron absorption and reduces gastrointestinal side effects 2
  • Morning dosing is preferred over afternoon/evening to avoid circadian hepcidin increases 2

Enhancing Absorption and Tolerability

• Take with ascorbic acid (vitamin C) to improve absorption, though evidence is limited 1, 2
• Avoid concurrent calcium supplements and antacids—separate by several hours as they significantly decrease iron absorption 1, 4
• Taking with food or using enteric-coated formulations improves tolerability but decreases absorption 1
• Consider bedtime dosing if gastrointestinal side effects are problematic 4

Monitoring Response

• Recheck hemoglobin after 1 month of treatment 1
• Expected response: hemoglobin increase ≥1 g/dL 4
• If no response after 1 month, assess for:
  • Non-adherence due to side effects 1
  • Malabsorption syndromes 1
  • Ongoing blood loss exceeding iron intake 1

Pregnant Women

Prophylaxis (All Pregnant Women)

• 30 mg elemental iron daily starting at first prenatal visit for universal prophylaxis 1, 4, 5
• Most prenatal vitamins contain 30-48 mg elemental iron, meeting this requirement 4, 5

Treatment of Confirmed Iron Deficiency Anemia

• 60-120 mg elemental iron daily as first-line treatment 4, 6
• Begin treatment immediately without waiting for additional confirmatory testing if patient is not acutely ill 4, 6
• Continue throughout pregnancy and into postpartum period 4, 6
• Recheck hemoglobin/hematocrit after 4 weeks 4, 6
• Once hemoglobin normalizes for gestational age, decrease to 30 mg/day 4

Special Considerations in Pregnancy

• Vegetarian women may require almost twice as much iron due to lower absorption of non-heme iron from plant sources 4, 6, 5
• Higher-risk groups (non-Hispanic Black and Mexican American women, short interpregnancy intervals, gastrointestinal conditions) may need closer monitoring and higher-dose prophylaxis 4, 6, 5
• Severe anemia (hemoglobin <9.0 g/dL or hematocrit <27.0%): refer to physician familiar with anemia management in pregnancy 4

Postpartum Management

• Screen for anemia at 4-6 weeks postpartum only if risk factors present (anemia continued through third trimester, excessive blood loss at delivery, multiple birth) 4, 6
• If no risk factors, discontinue iron supplementation at delivery 4
• For postpartum iron deficiency anemia, treat with 60-120 mg elemental iron daily and continue for 2-3 months after hemoglobin normalizes 4

Chronic Kidney Disease Patients

Diagnostic Criteria (Different from General Population)

• Absolute iron deficiency in CKD: transferrin saturation (TSAT) ≤20% AND 7
  • Serum ferritin ≤100 ng/mL (predialysis and peritoneal dialysis patients) 7
  • Serum ferritin ≤200 ng/mL (hemodialysis patients) 7
• Functional iron deficiency: TSAT ≤20% with elevated ferritin levels 7

Treatment Approach

• CKD stage 5D (on dialysis): Intravenous iron is the preferred method 7, 8
• CKD stages 3-5 (non-dialysis): Either intravenous or oral iron is recommended 7
  • Trial of oral iron for 1-3 months can be attempted 8
  • Oral iron is often insufficient in patients treated with erythropoiesis-stimulating agents 8
• High circulating hepcidin in CKD patients reduces iron bioavailability despite normal/high total iron content 8

Patients with History of Gastrointestinal Bleeding

Initial Approach

• Perform bidirectional endoscopy (gastroscopy and colonoscopy) to identify source 1, 3
• Test for H. pylori and celiac disease non-invasively before endoscopy 1, 3
• Treat underlying cause while simultaneously providing iron supplementation 1

Iron Supplementation Strategy

• Start oral iron 100-200 mg elemental iron daily 3
• Lower dose if side effects occur 3
• 3-6 months of oral iron therapy is often required to normalize hemoglobin and replenish iron stores 3

When to Use Intravenous Iron

Intravenous iron is appropriate in selected patients: 1

• Impaired absorption due to prior gastric surgery 1
• Inflammatory bowel disease 1
• Chronic kidney disease (especially dialysis patients) 1, 7
• Blood loss exceeds ability to replete iron orally 1
• Failure of oral iron therapy after 4 weeks despite compliance 6, 3
• Intestinal malabsorption or prolonged inflammation 3

IV Iron Formulations

• Ferric carboxymaltose is preferred in pregnancy due to rapid effectiveness and better tolerability 6
• Ferric gluconate (Ferrlecit): 9
  • Adult dose: 125 mg elemental iron diluted in 100 mL 0.9% saline over 1 hour per dialysis session 9
  • Pediatric dose (≥6 years): 1.5 mg/kg elemental iron diluted in 25 mL 0.9% saline over 1 hour per dialysis session 9
  • Monitor for hypersensitivity reactions during and for at least 30 minutes after administration 9
  • Administer only where resuscitation facilities are immediately available 6, 9

Consultation

• Consultation with hematologist is often helpful when intravenous iron repletion is required 1

Common Pitfalls to Avoid

• Failing to separate calcium supplements and antacids from iron doses by several hours, which significantly reduces absorption 4, 5
• Using daily dosing instead of alternate-day dosing for doses ≥60 mg, which reduces fractional absorption 2
• Giving afternoon/evening doses after a morning dose, which encounters elevated hepcidin 2
• Not identifying higher-risk women (vegetarians, certain ethnic groups, short interpregnancy intervals) who need increased supplementation 4, 5
• Discontinuing treatment too early before iron stores are replenished 4, 5
• Assuming low iron intake is the cause of anemia in men and postmenopausal women without investigating for gastrointestinal bleeding or chronic disease 1

Expected Side Effects

• Common gastrointestinal effects: nausea, constipation, diarrhea 4, 5
• Darkening of stool or urine (expected and harmless) 4, 5
• Possible staining of teeth and gums 4, 5