What are the recommended doses for medications used to manage Sickle Cell Disease?

Recommended Doses for Medications Used to Manage Sickle Cell Disease

Hydroxyurea is the first-line disease-modifying therapy for sickle cell disease, with a recommended starting dose of 15-20 mg/kg/day orally, which can be titrated up based on laboratory monitoring.1

Hydroxyurea Dosing and Monitoring

• Initial dosing for hydroxyurea is 15-20 mg/kg/day orally as a single daily dose for both adults and children with HbSS or Sβ0-thalassemia 1
• For infants as young as 9 months of age with HbSS or Sβ0-thalassemia, hydroxyurea should be initiated at this same dose even without clinical symptoms 1
• Dose adjustments are made based on laboratory monitoring every 1-3 months, depending on how long the patient has been taking the medication and whether they have attained a stable dose 1
• Myelosuppression is a potential adverse effect requiring regular monitoring of complete blood count (CBC) and reticulocyte count 1, 2
• Temporary discontinuation of hydroxyurea is recommended if bone marrow suppression occurs, with resumption at a lower dose after counts recover (typically within 2 weeks) 1

L-glutamine (Endari)

• Recommended for children 5 years and older to reduce pain events 1
• Administered as a powder packet mixed in liquid or food twice daily 1
• Does not require laboratory monitoring 1

Crizanlizumab (Adakveo)

• Recommended dose is 5 mg/kg intravenously 3
• Administration schedule: first two doses 2 weeks apart, then every 4 weeks thereafter 3
• Indicated for patients 16 years and older to reduce frequency of vaso-occlusive crises 3
• In clinical trials, crizanlizumab reduced pain crises from 2.98 to 1.63 per year compared with placebo 4

Penicillin Prophylaxis

• For infants with HbSS and Sβ0-thalassemia: 125 mg orally twice daily, starting by 2 months of age 1
• Increase to 250 mg orally twice daily at 3 years of age 1
• Continue until age 5 years or completion of pneumococcal vaccine series 1
• Alternative for penicillin allergy: erythromycin 1
• Amoxicillin 20 mg/kg/day can be substituted based on medication cost or taste preferences 1

Transfusion Therapy

• For chronic transfusion therapy, automated red cell exchange (RCE) is preferred over simple transfusion or manual RCE 1
• Target hemoglobin concentration of 10-12 g/dl is often attainable via chronic transfusion therapy 1
• Goal is to reduce HbS to less than 50% 1

Combination Therapy for Chronic Kidney Disease

• For patients with SCD and chronic kidney disease, combination therapy with hydroxyurea and erythropoiesis-stimulating agents is recommended 1
• This combination allows for more aggressive dosing of hydroxyurea while managing anemia 1
• Treatment thresholds for hemoglobin levels may need to be set lower for individuals with SCD given the theoretical risk for increased pain with higher hemoglobin levels 1

Immunosuppressive Therapy for Hemolytic Transfusion Reactions

• For delayed hemolytic transfusion reactions with hyperhemolysis:
  • First-line: High-dose steroids (methylprednisolone or prednisone at 1-4 mg/kg/day) and IVIg (0.4-1 g/kg/day for 3-5 days, up to total dose of 2 g/kg) 1
  • Second-line: Eculizumab (900-1200 mg weekly for adults >40 kg) for patients who continue to experience clinical deterioration despite first-line agents 1
  • Rituximab (375 mg/m² repeated after 2 weeks) may be used for prevention of additional alloantibody formation 1

Practical Considerations and Monitoring

• Hydroxyurea has been shown to increase total and fetal hemoglobin and decrease vaso-occlusive complications including episodes of painful events, acute chest syndrome, hospitalizations, and need for transfusion 1, 2, 5
• Long-term hydroxyurea use has been demonstrated to be safe, even when initiated in early infancy and continued for more than a decade 1
• Patients on chronic transfusion therapy will require iron chelation after 12-20 transfusions to treat iron overload 1
• For patients experiencing splenic sequestration crisis, prompt recognition and careful administration of red blood cell transfusions (3-5 mg/kg) are recommended, with post-transfusion hemoglobin checked before the next aliquot of red cells is ordered 6

Common Pitfalls and Caveats

• Avoid overtransfusion to a hemoglobin greater than 10 g/dL in splenic sequestration crisis, as sequestered red cells may be acutely released from the spleen as the event resolves 6
• For patients with SCD undergoing surgery, dehydration must be avoided, particularly in those with pre-existing renal dysfunction 1
• When administering immunosuppressive therapy for hemolytic transfusion reactions, immediate vaccination with meningococcal vaccines and ciprofloxacin prophylaxis are advised if using eculizumab to reduce the risk for meningococcal infection 1
• Folic acid supplementation is no longer needed given the widespread supplementation of formula and grain products in the western world 1