What is the recommended dose of iron for Restless Leg Syndrome (RLS)?

Iron Supplementation for Restless Legs Syndrome

Iron supplementation should be provided for patients with Restless Legs Syndrome (RLS) when serum ferritin is ≤75 ng/mL or transferrin saturation is <20%, with oral iron as first-line therapy and intravenous iron formulations for those with ferritin between 75-100 ng/mL or when oral supplementation is ineffective. 1, 2, 3

Assessment of Iron Status

• Iron studies should be regularly tested in all patients with clinically significant RLS, including ferritin and transferrin saturation 1, 2
• Testing should ideally be done in the morning, avoiding all iron-containing supplements and foods for at least 24 hours prior to blood draw 1, 4
• Iron supplementation guidelines for RLS patients differ from the general population, with intervention recommended at higher ferritin levels (≤75 ng/mL rather than lower thresholds used for general anemia) 1, 2

Iron Supplementation Recommendations

Oral Iron Therapy

• Oral ferrous sulfate is recommended as first-line therapy for patients with RLS and iron deficiency parameters (ferritin ≤75 ng/mL or transferrin saturation <20%) 2, 3
• The recommended daily dose of oral iron for adults is at least 200 mg of elemental iron 4
• Monitor for adverse effects of oral iron, which commonly include gastrointestinal symptoms such as constipation 4, 5

Intravenous Iron Therapy

• IV iron formulations should be considered if oral iron is ineffective or poorly tolerated 2, 3
• The American Academy of Sleep Medicine strongly recommends IV ferric carboxymaltose for patients with appropriate iron parameters (strong recommendation, moderate certainty) 1, 2
• IV iron is conditionally recommended for patients with ferritin between 75-100 ng/mL 1, 2
• IV low molecular weight iron dextran and IV ferumoxytol are conditionally recommended alternatives 1

Special Populations

• For pediatric RLS patients, iron supplementation is recommended when serum ferritin is <50 ng/mL 2
• For patients with end-stage renal disease and RLS, IV iron sucrose is conditionally recommended if ferritin <200 ng/mL and transferrin saturation <20% 2, 3
• A meta-analysis found that IV iron therapy was associated with improvement in both RLS severity scores and quality of life measures 5

Safety Considerations

• Always check iron studies before initiating iron therapy to avoid potential complications in patients with hemochromatosis or iron overload conditions 6
• If hemoglobin rises significantly during iron therapy, treatment should be temporarily discontinued and the patient evaluated for other causes of polycythemia 4
• While iron therapy is associated with an increased rate of adverse events compared to placebo, these are generally not severe and typically do not require treatment discontinuation 5, 7

Additional Management Considerations

• Address potential exacerbating factors for RLS, such as alcohol, caffeine, antihistaminergic, serotonergic, and antidopaminergic medications 1, 2
• If iron therapy alone is insufficient, alpha-2-delta ligands (gabapentin, gabapentin enacarbil, pregabalin) are recommended as first-line pharmacologic therapy 2, 3
• Dopamine agonists are no longer recommended as first-line therapy due to the risk of augmentation with long-term use 2, 3

Monitoring During Treatment

• Regular follow-up of iron studies is recommended to assess response to therapy and adjust treatment as needed 1, 4
• For patients on oral iron therapy who do not respond adequately after 3 months, consider switching to IV iron formulations 2, 7