From the Guidelines
For patients with sickle cell disease who are allergic to hydroxyurea, the most effective alternative medications are Voxelotor (Oxbryta), Crizanlizumab (Adakveo), and L-glutamine (Endari), as they have been shown to reduce sickling and its complications through different mechanisms 1.
Alternative Medications
- Voxelotor is taken orally at 1,500 mg daily and works by preventing hemoglobin polymerization.
- Crizanlizumab is administered intravenously at 5 mg/kg on weeks 0, 2, and then every 4 weeks thereafter; it reduces vaso-occlusive crises by blocking P-selectin adhesion.
- L-glutamine is taken orally at 5-15 grams twice daily (based on weight) and reduces oxidative stress in red blood cells.
Considerations
These medications can be used alone or in combination depending on disease severity. Blood transfusions remain another important option, particularly for acute complications or when medication therapy is insufficient. The choice between these alternatives should be based on the patient's specific symptoms, disease severity, comorbidities, and access to care. Unlike hydroxyurea, which primarily increases fetal hemoglobin production, these newer agents work through different mechanisms to reduce sickling and its complications. According to the American Society of Hematology 2021 guidelines, these alternatives are preferred over hematopoietic stem cell transplantation, which is a potential curative therapy, but with significant risks and limited donor availability 1.
From the FDA Drug Label
The efficacy of L-glutamine in sickle cell disease was evaluated in a randomized, double-blind, placebo-controlled, multi-center clinical trial entitled "A Phase III Safety and Efficacy Study of L-Glutamine to Treat Sickle Cell Disease or Sickle β0-thalassemia" [NCT01179217] Eligible patients stabilized on hydroxyurea for at least 3 months continued their therapy throughout the study Efficacy was demonstrated by a reduction in the number of sickle cell crises through Week 48 and prior to the start of tapering among patients that received L-glutamine compared to patients who received placebo. This clinical benefit was observed irrespective of hydroxyurea use
For patients with sickle cell disease who are allergic to hydroxyurea, L-glutamine is an alternative treatment option, as demonstrated by a reduction in sickle cell crises in a clinical trial 2.
- Key benefits of L-glutamine include: + Reduction in sickle cell crises + Fewer hospitalizations due to sickle cell pain + Fewer cumulative days in hospital + Lower incidence of acute chest syndrome Another alternative is voxelotor, which is used for the treatment of sickle cell disease in adults and children 4 years of age and older 3.
From the Research
Alternative Treatments for Sickle Cell Disease
Allergic reactions to hydroxyurea can be a significant concern for patients with sickle cell disease. Fortunately, there are alternative treatments available. Some of these alternatives include:
- Voxelotor: a first-in-class small-molecule agent that binds to Hb and increases oxygen affinity, preventing polymerization 4
- Crizanlizumab: associated with a reduction in pain crises and time to first crisis, with reduction in need for opioid use 5
- L-glutamine: associated with decrease in pain crises, hospitalizations, and time to first and second crises, with a decrease in RBC transfusion rate 5
Comparison of Alternative Treatments
Each of these alternative treatments has its own unique characteristics, benefits, and drawbacks. For example:
- Voxelotor has been shown to increase Hb concentration and reduce hemolysis in patients with SCD 4
- Crizanlizumab has been associated with adverse effects such as headache, nausea, and infusion reactions 5
- L-glutamine has been associated with barriers to use such as insurance denial, high deductible, and intolerability, especially abdominal pain 5
Considerations for Treatment Selection
When selecting an alternative treatment for sickle cell disease, several factors should be considered, including: