1.1. Adults

Current therapeutic options available for the outpatient management of sickle cell disease include hydroxyurea (Droxia®, Siklos®), L-glutamine (Endari®), and voxelotor (Oxbryta®). Hydroxyurea is a chemotherapeutic agent used to stimulate red blood cell (RBC) fetal hemoglobin (HbF) production, which is associated with a lower risk of acute sickle cell complications. Although the exact mechanism of action for sickle cell disease is unknown, hydroxyurea is FDA approved for patients with recurrent moderate-to-severe painful crises to reduce the frequency of painful crises and the need for blood transfusions. However, hydroxyurea cannot be used to treat crises1-7. L-glutamine is an essential amino acid thought to decrease oxidative damage to sickled RBCs by increasing nicotinamide adenine dinucleotide (NAD+) synthesis, thereby reducing the complications of sickle cell disease such as chronic hemolysis and vasoocclusive events.1-5,8 Voxelotor is a first-in-class hemoglobin S (HbS) polymerization inhibitor which increases the affinity of HbS for oxygen by stabilizing the oxygenated hemoglobin state2-5,9.

Maximum recommended adult dosages are summarized in Table 1. Medication profiles identifying patients prescribed dosages exceeding these recommendations will be reviewed.

Table 1: Maximum Daily Adult Dosages for Sickle Cell Disease Products2-9
Drug Name Dosage Form/Strength Treatment Indication Maximum Recommended Dosage
hydroxyurea (Droxia®) 200 mg, 300 mg, 400 mg capsules Reduction in frequency of painful crises and to reduce the need for blood transfusions in patients with moderate to severe painful crises 35 mg/kg/day as long as blood counts are within acceptable range
hydroxyurea (Siklos®) 100 mg, 1000 mg tablets Reduction in frequency of painful crises and to reduce the need for blood transfusions in patients with moderate to severe painful crises 35 mg/kg/day as long as blood counts are within acceptable range
L-glutamine (Endari®) 5 gram powder packets Reduction in acute complications of sickle cell disease

Based on patient weight:

Less than 30 kg 5 g twice daily 30-65 kg 10 g twice daily

Greater than 65 kb 15 g twice daily
voxelotor (Oxbryta®) 500 mg tablets Treatment of sickle cell disease 1500 mg once daily+

Legend:

  • + voxelotor dose should be increased to 2000 mg once daily if prescribed with a moderate CYP3A4 inducer and 2500 mg once daily if prescribed concurrently with strong CYP3A4 inducers or reduced to 1000 mg once daily in patients with severe hepatic impairment