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 crises [1-5]. 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, 4]. Voxelotor is a first-in-class hemoglobin S (HbS) polymerization inhibitor which increases the affinity of HbS for oxygen by stabilizing the oxygenated hemoglobin state [1, 5]. Several products have been introduced to the market that will not be covered under Texas pharmacy benefits including crizanlizumab (Adakveo), exagamglogene (Casgevy), and lovotibeglogene (Lyfgenia). Crizanlizumab is a selectin blocker requiring intravenous infusion administered by a healthcare professional. Exagamglogene and lovotibeglogene are single dose gene therapies [1, 6-8].
Maximum recommended adult dosages are summarized in Table 1. Medication profiles identifying patients prescribed dosages exceeding these recommendations will be reviewed.
| 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