What is the recommendation for iron infusion in a patient with Restless Legs Syndrome (RLS) and iron deficiency, with a ferritin level indicating hypoferritinemia?

From the Guidelines

Iron infusion is recommended for patients with Restless Legs Syndrome (RLS) and iron deficiency when ferritin levels are below 75 ng/mL, especially if oral iron supplementation has failed or isn't tolerated. The patient in question has a ferritin level of 37 ng/mL, which is below the recommended threshold. According to the American Academy of Sleep Medicine clinical practice guideline 1, iron supplementation should be instituted with oral or IV iron if serum ferritin is ≤ 75 ng/mL or transferrin saturation < 20%.

The typical regimen involves intravenous iron preparations such as iron sucrose (200-300 mg per session), ferric carboxymaltose (500-1000 mg per dose), or iron dextran (1000 mg total dose infusion) 1. Treatment usually requires 1-2 infusions, with potential follow-up infusions based on clinical response and ferritin levels. Before starting infusion therapy, patients should undergo baseline complete blood count and iron studies. During administration, vital signs should be monitored for potential infusion reactions.

Iron infusions work by rapidly replenishing iron stores, which is essential for dopamine synthesis in the brain. Dopamine dysfunction is central to RLS pathophysiology, and adequate iron is required as a cofactor for tyrosine hydroxylase, the rate-limiting enzyme in dopamine production. This approach is particularly effective when oral iron hasn't improved symptoms or when rapid correction of iron deficiency is needed for severe RLS symptoms. The use of IV ferric carboxymaltose is strongly recommended for adults with RLS and iron deficiency 1.

Some key points to consider when administering iron infusions include:

• Monitoring for potential infusion reactions
• Baseline complete blood count and iron studies before starting infusion therapy
• Potential follow-up infusions based on clinical response and ferritin levels
• The importance of iron in dopamine synthesis and RLS pathophysiology
• The effectiveness of iron infusions in rapidly replenishing iron stores and improving RLS symptoms.

It's also important to note that iron treatment is an important addition to the management of RLS, and determining better approaches to evaluate brain iron deficiency and the patient populations more likely to respond to iron treatment are needed 1.

From the FDA Drug Label

Injectafer is indicated for the treatment of: • iron deficiency anemia (IDA) in: adult and pediatric patients 1 year of age and older who have either intolerance or an unsatisfactory response to oral iron. The patient has Restless Legs Syndrome (RLS) and iron deficiency with a ferritin level of 37, indicating hypoferritinemia.

• The primary indication for iron infusion is iron deficiency anemia (IDA) or iron deficiency in specific patient populations.
• The recommended dosage for IDA is Injectafer 750 mg intravenously in two doses separated by at least 7 days for a total cumulative dose of 1,500 mg of iron per course.
• However, there is no direct information in the provided drug label that specifically addresses the use of iron infusion for RLS patients with low ferritin levels.
• Given the lack of direct evidence, it is unclear if iron infusion is recommended for this patient.
• A conservative clinical decision would be to consider alternative treatments or consult additional resources before making a decision about iron infusion for this patient 2.

From the Research

Recommendation for Iron Infusion in Patients with RLS and Low Iron

The recommendation for iron infusion in patients with Restless Legs Syndrome (RLS) and iron deficiency, with a ferritin level indicating hypoferritinemia, can be based on several studies.

• A study published in 2019 3 found that intravenous iron was more efficacious than placebo in treating RLS, with a significant decrease in IRLS score after IV iron treatment.
• Another study from 2012 4 showed that IV ferric carboxymaltose improved RLS severity in patients with absolute or functional iron deficiency or low normal serum ferritin, with a significant decrease in IRLS score three weeks after treatment.
• A 2017 study 5 compared the efficacy and tolerability of ferric carboxymaltose versus placebo for RLS treatment in iron-deficient nonanemic patients and found that ferric carboxymaltose treatment led to a significant improvement in IRLS score at week 12.

Ferritin Levels and Iron Infusion

• The studies suggest that iron infusion can be beneficial for patients with RLS and low ferritin levels, even if the levels are not severely low.
• For example, a study from 2012 4 included patients with serum ferritin <45 μg/l, and a 2017 study 5 included patients with serum ferritin <75 μg/L.
• In the case of a patient with a ferritin level of 37, iron infusion may be considered as a treatment option for RLS, based on the findings of these studies 3, 4, 5.

Safety and Efficacy of Iron Infusion

• The studies also suggest that iron infusion is generally safe and well-tolerated in patients with RLS and iron deficiency.
• A 2019 study 3 found that adverse events did not differ significantly between patients receiving intravenous iron or placebo.
• A 2022 study 6 found that IV ferric carboxymaltose was effective and safe in children with autism spectrum disorder and RLS symptoms, with significant improvement in symptoms and serum iron parameters after treatment.

Comparison with Oral Iron

• A 2009 study 7 found that oral iron replacement was effective in improving RLS symptoms in patients with low-normal serum ferritin levels.
• However, the studies suggest that iron infusion may be a more effective treatment option for patients with RLS and iron deficiency, especially those with severe symptoms or who have not responded to oral iron therapy 3, 4, 5.