What other medications are used to treat adult patients with sickle cell disease, in addition to hydroxyurea?

Medications for Sickle Cell Disease Beyond Hydroxyurea

In addition to hydroxyurea, the primary medications used for adults with sickle cell disease include chronic transfusion therapy, erythropoiesis-stimulating agents (for those with chronic kidney disease), crizanlizumab (for reducing vaso-occlusive crises), and iron chelation therapy (for transfusion-related iron overload). 1, 2

Disease-Modifying Therapies

Chronic Transfusion Therapy

• Chronic transfusions are strongly recommended for adults with sickle cell disease who have had a stroke or are at high risk for stroke, with the goal of maintaining sickle hemoglobin levels below 30% prior to the next transfusion. 3
• For patients with elevated mortality risk (tricuspid regurgitant velocity ≥2.5 m/second or elevated NT-pro-BNP), chronic transfusions represent an alternative therapy when hydroxyurea is not tolerated or effective. 1
• Preoperative transfusion to increase hemoglobin to 10 g/dL is strongly recommended before surgery. 3

Crizanlizumab (ADAKVEO)

• Crizanlizumab is FDA-approved at 5 mg/kg intravenously on Week 0, Week 2, then every 4 weeks thereafter to reduce the frequency of vaso-occlusive crises in adults and adolescents aged 16 years and older. 2
• In the SUSTAIN trial, crizanlizumab reduced the median annual rate of vaso-occlusive crises from 2.98 to 1.63 compared to placebo (p=0.010), with 36% of treated patients experiencing no crises versus 17% on placebo. 2
• Crizanlizumab can be used with or without concurrent hydroxyurea therapy. 2

Combination Therapies for Specific Complications

Erythropoiesis-Stimulating Agents (ESAs)

• For adults with sickle cell disease and worsening anemia due to chronic kidney disease, combination therapy with hydroxyurea plus erythropoiesis-stimulating agents is recommended over hydroxyurea alone. 1
• ESAs are appropriate when there is a simultaneous drop in both hemoglobin and absolute reticulocyte count in patients already on steady-state hydroxyurea. 1
• Critical safety threshold: Never exceed hemoglobin of 10 g/dL (hematocrit 30%) to reduce the risk of vaso-occlusive complications, stroke, and venous thromboembolism. 1, 4
• The combination allows for more aggressive hydroxyurea dosing and higher fetal hemoglobin levels. 1, 4

Iron Chelation Therapy

• For patients receiving chronic transfusions who develop iron overload, screen with MRI (R2, T2, or R2) for liver iron content every 1-2 years rather than relying on ferritin levels alone.** 4
• Add cardiac T2* MRI screening if liver iron content exceeds 15 mg/g dry weight for 2 years or more. 4
• Iron chelation can be titrated based on MRI findings regardless of ferritin level. 4

Anticoagulation for Venous Thromboembolism

VTE Management

• For adults with sickle cell disease and first unprovoked venous thromboembolism, indefinite anticoagulation is recommended over shorter, defined periods. 1
• For first provoked VTE (surgical or nonsurgical), use defined periods of anticoagulation (3-6 months) rather than indefinite therapy. 1
• For recurrent provoked VTE, indefinite anticoagulation is recommended. 1

Pulmonary Hypertension-Specific Considerations

PAH-Targeted Therapies

• For most patients with sickle cell disease and elevated tricuspid regurgitant velocity or elevated NT-pro-BNP alone, PAH-specific therapy is strongly contraindicated. 1
• For highly select patients with right heart catheterization-confirmed pulmonary hypertension who have elevated pulmonary vascular resistance and normal pulmonary capillary wedge pressure, prostacyclin agonists or endothelin receptor antagonists may be considered. 1
• Phosphodiesterase-5 inhibitors are strongly contraindicated in sickle cell disease patients with pulmonary hypertension. 1

Important Medication Interactions and Precautions

Hydroxyurea Continuation

• Do not discontinue hydroxyurea when initiating doxycycline or other antibiotics. 5, 4
• Hydroxyurea has no documented hepatotoxicity and can be continued in patients with liver complications. 4
• Only suspend hydroxyurea if severe myelosuppression develops (decreased counts in one or more cell lines), and resume at a lower dose after resolution. 5, 4

Blood Pressure Management

• For adults with sickle cell disease, target blood pressure of ≤130/80 mm Hg rather than ≤140/90 mm Hg, following general population guidelines for African American individuals. 1