Iron Supplementation for Ferritin <50 ng/mL
For patients with ferritin <50 ng/mL, start with oral ferrous sulfate 325 mg daily (65 mg elemental iron) or on alternate days, which provides adequate iron repletion for most patients without chronic inflammatory conditions. 1, 2, 3
Oral Iron as First-Line Therapy
Oral ferrous sulfate 325 mg daily (equivalent to 65 mg elemental iron) is the standard initial dose for adults with iron deficiency when ferritin is <50 ng/mL 1, 2, 3
Alternate-day dosing (325 mg every other day) may improve absorption and reduce gastrointestinal side effects while maintaining therapeutic efficacy 1
Pediatric patients require 2-3 mg/kg of elemental iron daily 1
Ferrous iron (Fe2+) is absorbed 4-10 times better than ferric iron (Fe3+), making ferrous sulfate superior to ferric compounds like ferric gluconate 4
Common side effects include constipation, diarrhea, and nausea, which occur less frequently with alternate-day dosing 1
When to Use Intravenous Iron Instead
IV iron should be the initial choice rather than oral iron in specific clinical scenarios:
Chronic kidney disease patients (both dialysis and non-dialysis dependent) typically require IV iron to maintain adequate iron stores 1
Heart failure patients with ferritin <100 ng/mL or transferrin saturation <20% 1, 3
Inflammatory bowel disease patients, where oral iron absorption is impaired 1, 5, 3
Second and third trimester pregnancy, when rapid iron repletion is needed 3
Patients intolerant to oral iron or with documented poor absorption (celiac disease, post-bariatric surgery) 1, 3
Ongoing blood loss that exceeds oral iron replacement capacity 1, 3
IV Iron Dosing When Indicated
For patients requiring IV iron with ferritin <50 ng/mL:
Ferric carboxymaltose: 1000 mg IV over 15 minutes (can repeat up to 1000 mg per week if needed) is the most efficient option 1, 5, 6
Iron dextran: 500-1000 mg IV as a single infusion after a 25 mg test dose in adults (10-15 mg test dose in children) 1
For hemodialysis patients: 100-125 mg IV weekly for 8-10 doses until ferritin reaches ≥100 ng/mL and transferrin saturation ≥20% 1
Iron sucrose: 200-500 mg IV with minimum infusion time of 30-210 minutes, though less effective than ferric carboxymaltose 1, 5
Monitoring Response
Recheck ferritin and transferrin saturation after 8-10 weeks of oral iron therapy to assess response 1
Do not recheck iron parameters immediately after IV iron infusion: wait 2 weeks after doses ≥1000 mg, or 7 days after 200-500 mg doses 1
Target ferritin ≥100 ng/mL and transferrin saturation ≥20% for patients on erythropoiesis-stimulating agents 1
For general iron deficiency without CKD: target ferritin ≥50 ng/mL, as this represents the physiologic threshold for adequate iron stores 7
Critical Pitfalls to Avoid
Do not use high-molecular weight ferric hydroxide-carbohydrate complexes orally—they are poorly absorbed and therapeutically useless 4
Ferritin <50 ng/mL indicates depleted iron stores even in the absence of anemia, and treatment should not be delayed until anemia develops 3, 7
In inflammatory conditions (cancer, IBD, CKD), ferritin cutoffs should be raised to <100 ng/mL to diagnose iron deficiency, as ferritin is an acute phase reactant 1
Most hemodialysis patients cannot maintain adequate iron status with oral iron alone and will require regular IV iron supplementation 1
Stop IV iron if ferritin exceeds 800 ng/mL or transferrin saturation exceeds 50% to avoid iron overload 1