What iron and vitamin D supplements to order for a patient with suspected iron and vitamin D deficiency?

Iron and Vitamin D Supplementation Recommendations

For iron deficiency, prescribe ferrous sulfate 200 mg (65 mg elemental iron) twice daily taken on an empty stomach in the morning with vitamin C, and for vitamin D deficiency, prescribe cholecalciferol 50,000 IU weekly for 8-12 weeks followed by 800-2,000 IU daily maintenance. 1, 2

Iron Supplementation Protocol

First-Line Oral Iron Therapy

• Prescribe ferrous sulfate 200 mg tablets (containing 65 mg elemental iron) twice daily 1, 3
• Lower doses may be equally effective and better tolerated—consider starting with 200 mg once daily if tolerability is a concern 1
• Continue oral iron for 3 months after iron deficiency is corrected to replenish stores 1

Optimal Dosing Strategy for Maximum Absorption

• Administer iron in the morning on an empty stomach with approximately 100 mg vitamin C (as a tablet or glass of orange/citrus juice) 4
• Consider alternate-day dosing rather than consecutive daily dosing—this increases fractional iron absorption from 16.3% to 21.8% and reduces side effects 5
• If twice-daily dosing is used, separate doses by at least 8-9 hours, though single daily dosing optimizes absorption better 5
• Separate calcium supplements and iron by at least 2 hours as calcium inhibits iron absorption 1, 2

What Impairs Iron Absorption (Avoid These)

• Afternoon dosing reduces absorption compared to morning administration 4
• Food (especially cereals, grains), milk, tea, and coffee markedly reduce absorption 4
• Antacids, H2 inhibitors, and proton pump inhibitors decrease absorption 4
• In patients with active inflammatory disease, limit to no more than 100 mg elemental iron daily as inflammation inhibits absorption 1

Alternative Iron Formulations

• Slow-release ferrous sulfate formulations are recommended as most effective and tolerable 1
• Alternative compounds include ferrous fumarate 210 mg or ferrous gluconate 300 mg daily if ferrous sulfate is not tolerated 1

When to Use Intravenous Iron

• Reserve IV iron for patients intolerant of oral iron, those with active inflammatory disease and moderate-to-severe anemia (Hb <100 g/L), or those with enteral absorption disruption 1
• IV options include iron sucrose (Venofer) 200 mg over 10 minutes, ferric carboxymaltose (Ferinject) 1000 mg over 15 minutes, or iron dextran (Cosmofer) 20 mg/kg over 6 hours 1
• Resuscitation facilities must be available due to anaphylaxis risk 1

Vitamin D Supplementation Protocol

Loading Phase for Deficiency (25-OH-D <30 ng/mL)

• Prescribe cholecalciferol (vitamin D3) 50,000 IU weekly for 8-12 weeks 2, 6
• Cholecalciferol (D3) is strongly preferred over ergocalciferol (D2) because it maintains serum levels longer and has superior bioavailability 2
• Recheck 25-OH-D levels after 3 months of treatment to confirm adequate response 2

Maintenance Therapy

• After achieving target levels ≥30 ng/mL, prescribe 800-2,000 IU daily 2, 6
• Alternative: 50,000 IU monthly (equivalent to approximately 1,600 IU daily) 2
• Note that 2,000 IU daily maintenance may be insufficient for some patients—one study showed levels dropped from 37 ng/mL to 20 ng/mL on this dose, suggesting higher maintenance doses (2,000-4,000 IU daily) may be needed 1, 7

Calcium Co-Supplementation

• Ensure adequate calcium intake of 1,000-1,500 mg daily from diet plus supplements as calcium is necessary for clinical response to vitamin D therapy 2
• Divide calcium doses to no more than 600 mg at once for optimal absorption 2
• Calcium citrate is preferred over calcium carbonate, especially for patients at risk of kidney stones 1

Safety Considerations

• Daily vitamin D doses up to 4,000 IU are generally safe, with upper safety limit for 25-OH-D being 100 ng/mL 2
• Avoid single very large doses (>300,000 IU) as they may be inefficient or harmful 2
• Do not use active vitamin D analogs (calcitriol, alfacalcidol) to treat nutritional deficiency—these are reserved for advanced chronic kidney disease 2

Can Iron and Vitamin D Be Given Together?

Yes, iron and vitamin D can be administered at the same time without affecting treatment efficacy. 8

• A pediatric study demonstrated no difference in anemia recovery whether vitamin D prophylaxis was given simultaneously with iron or at different times 8
• Administering both together improves medication compliance 8
• However, maintain the 2-hour separation between iron and calcium supplements if calcium is being co-administered with vitamin D 1, 2

Monitoring and Follow-Up

• Recheck hemoglobin and iron studies after 8-12 weeks of iron therapy 1
• Recheck 25-OH-D levels 3 months after initiating vitamin D supplementation 2
• If target hemoglobin is not achieved with oral iron, consider further evaluation for ongoing blood loss or malabsorption 1
• Monitor for ferritin levels up to 100 µg/L in presence of inflammation, as this may still reflect iron deficiency—transferrin saturation measurement may be helpful 1

Common Pitfalls to Avoid

• Do not initiate empiric iron supplementation without physician evaluation—this could mask severe underlying disease 1
• Avoid dosing iron with food, tea, coffee, or milk as this dramatically reduces absorption 4
• Do not assume standard maintenance vitamin D doses (800-1,000 IU) will maintain levels in all patients—some require 2,000-4,000 IU daily 1, 7
• Avoid administering iron tablets without adequate fluid and ensure patient remains upright for 30-60 minutes to prevent pill esophagitis 4