In a 28‑year‑old woman with ferritin rising from 9 ng/mL to 22 ng/mL after three months of over‑the‑counter oral iron, what is the preferred prescription oral iron formulation, dosing schedule, and is there a combined iron‑vitamin C product available?

Prescription Iron for Iron Deficiency Anemia

For your 28-year-old patient with persistent iron deficiency (ferritin 22 ng/mL after 3 months of OTC iron), prescribe ferrous sulfate 200 mg (65 mg elemental iron) once daily, taken on an empty stomach, and there is no need for a combined iron-vitamin C prescription product. 1

Optimal Prescription Iron Dosing

The most recent British Society of Gastroenterology guidelines (2021) recommend a once-daily dose of 50–100 mg elemental iron (equivalent to one ferrous sulfate 200 mg tablet) taken in the fasting state as the best initial treatment approach. 1

Key Dosing Principles:

• Once-daily dosing is superior to multiple daily doses because hepcidin levels rise after iron intake and remain elevated for up to 48 hours, blocking further absorption. 1

• Ferrous sulfate 200 mg tablets (containing ~65 mg elemental iron) are the most cost-effective first-line option, though ferrous gluconate and ferrous fumarate are equally effective. 1

• Fasting administration (without food) maximizes absorption, though some patients tolerate taking it with meals better. 1

• Alternate-day dosing (e.g., 120 mg elemental iron every other day) produces similar hemoglobin increments with significantly lower nausea rates compared to twice-daily dosing, though it may be less effective for rapidly replenishing stores. 1

Vitamin C Supplementation: Not Routinely Necessary

There is no prescription product combining iron with vitamin C that offers meaningful clinical advantage. The evidence on vitamin C co-administration is mixed:

• Older guidelines suggested ascorbic acid enhances iron absorption and should be considered when response is poor. 1

• However, a 2020 randomized trial (n=440) demonstrated that oral iron alone was equivalent to iron plus vitamin C for hemoglobin recovery (mean difference only 0.16 g/dL), meeting equivalence criteria. 2

• A 2024 meta-analysis confirmed vitamin C supplementation produced only a clinically insignificant increase in hemoglobin (MD 0.14 g/dL) and does not support routine supplementation. 3

• The 2024 AGA Clinical Practice Update notes that while 80 mg ascorbic acid on an empty stomach may improve absorption, evidence is mixed and further study is needed. 1

Practical approach: If you want to optimize absorption, advise the patient to take 500 mg vitamin C separately (not as a prescription combination product) or consume vitamin C-rich foods, but this is optional rather than essential. 1

Monitoring and Response Assessment

• Recheck hemoglobin in 2–4 weeks: Absence of at least 10 g/L (1 g/dL) rise after 2 weeks of daily oral iron predicts subsequent treatment failure with 90% sensitivity. 1

• Monitor every 4 weeks until hemoglobin normalizes. 1

• Continue iron for 2–3 months after hemoglobin correction to replenish stores. 1

• Follow-up monitoring: Check CBC every 3 months for 1 year, then every 6–12 months. 1

When to Consider Intravenous Iron

Switch to IV iron if: 1

• No adequate hemoglobin response after 2 weeks of oral therapy
• Intolerance to at least two different oral preparations
• Chronic disease, continuing blood loss, or GI inflammatory pathology (where parenteral iron is more effective than oral therapy)
• Patient preference in cases of severe intolerance

Available IV formulations include ferric carboxymaltose (1000 mg single dose, 15-minute infusion), ferric derisomaltose, iron sucrose, and iron dextran. 1

Common Pitfalls to Avoid

• Don't prescribe multiple daily doses: This increases side effects without improving absorption due to hepcidin elevation. 1

• Don't switch between different ferrous salts for intolerance: This practice is not evidence-based; consider alternate-day dosing, ferric maltol, or IV iron instead. 1

• Don't forget to investigate the underlying cause: In a 28-year-old woman, evaluate menstrual blood loss, dietary intake, and consider testing for celiac disease and H. pylori if response is inadequate. 1, 4

• Avoid tea and coffee within 1 hour of iron intake: These are powerful inhibitors of absorption. 1