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 patients [1-5]. Hydroxyurea (Siklos) is approved for patients 2 years of age and older to reduce the frequency of recurrent moderate-to-severe painful crises [1, 3]. 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 years [1, 3]. L-glutamine is approved for pediatric patients 5 years and older, while voxelotor is approved for patients 4 years of age and older [1, 4, 5].

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 Products [1, 3-5]

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®)	300 mg tablets 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 Inducers [1,5]

Body Weight	Concomitant Use of Strong CYP3A4 Inducers	Concomitant Use of Moderate CYP3A4 Inducers
10 kg to less than 20 kg	900 mg	900 mg
20 kg to less than	40 kg	1500 mg    1200 mg
40 kg or greater	2500 mg (five 500 mg tablets) or 2400 mg (eight 300 mg tablets for oral suspension or tablets)	2000 mg (four 500 mg tablets) OR 2100 mg (seven 300 mg tablets for oral suspension or tablets)

Table 4: Recommended Daily Dosage of Voxelotor (Oxbryta) for Patients 4 Years to Less Than 12 Years with Severe Hepatic Impairment (Child-Pugh C) [1,5]

Body Weight	Recommended Dose (once daily)
10 kg to less than 20 kg	300 mg
20 kg to less than 40 kg	600 mg
40 kg or greater	1000 mg (two 500 mg tablets) OR 900 mg (three 300 mg tablets for oral suspension or tablets)