1.2. Pediatrics

L-glutamine (Endari®), voxelotor (Oxbryta®), and hydroxyurea as Siklos® have been approved for use in pediatric patients, but the safety and efficacy of hydroxyurea (Droxia®) has not been established in pediatric patients6-10. Hydroxyurea (Siklos®) is approved for patients 2 years of age and older to reduce the frequency of recurrent moderate-to-severe painful crises7. Growth should be continuously monitored in pediatric patients prescribed hydroxyurea; additionally, pediatric patients 2-16 years of age are at greater risk of developing neutropenia compared to patients older than 16 years7. L-glutamine is approved for pediatric patients 5 years and older, while voxelotor is approved for patients 4 years of age and older2,8,9 .

The maximum recommended pediatric dose for individual agents is summarized in Table 2. Table 3 provides dosing recommendations for patients 4 years of age to less than 12 years of age while taking concomitant strong or moderate CYP3A4 inducers while taking voxelotor therapy. Table 4 provides dosing recommendations for patients 4 years of age to less than 12 years of age with severe hepatic impairment (Child-Pugh Class C) while taking voxelotor therapy. Prescribed dosages exceeding these recommendations will be reviewed.

Table 2: Maximum Daily Pediatric Dosages for Sickle Cell Disease Products2-9
Drug Name Dosage Form/Strength Treatment Indication Maximum Recommended Dosage 
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 2-17 years of age: 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

5 – 17 years of age: 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, 300 mg tablet for suspension Treatment of sickle cell disease
  • 4 – 11 years of age:
    • 40 kg or greater: 1,500 mg
    • 2 – 39 kg: 900 mg
    • 10 – 19 kg: 600 mg+
  • 12 years of age and older:
    • 1500 mg+

Legend:

  • +Voxelotor for those 12 years of age and older: dose should be increased to 2000mg 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.9 Further recommendations can be found for children less than 12 years of age in Table 3 and Table 4.
Table 3: Recommended Daily Dosage of Voxelotor (Oxbryta®) for Patients 4 Years to Less Than 12 Years When Used with Concomitant Strong or Moderate CYP3A4 Inducers9
Body Weight Concomitant Use of Strong CYP3A4 Inducers Concomitant Use of Moderate CYP3A4 Inducers
40 kg or greater 2500 mg (five 500 mg tablets) or 2400 mg (eight 300 mg tablets for oral suspension) 2000 mg (four 500 mg tablets) OR 2100 mg (seven 300 mg tablets for oral suspension)
20 kg to less than 40 kg 1500 mg    1200 mg
10 kg to less than 20 kg 900 mg 900 mg
Table 4: Recommended Daily Dosage of Voxelotor (Oxbryta®) for Patients 4 Years to Less Than 12 Years with Severe Hepatic Impairment (Child-Pugh C)9
Body Weight Recommended Dose (once daily)
40 kg or greater 1000 mg (two 500 mg tablets) OR 900 mg (three 300 mg tablets for oral suspension)
20 kg to less than 40 kg 600 mg
10 kg to less than 20 kg 300 mg