1.2. Pediatrics

Since the last update, several new therapies have been approved by the FDA, and several therapies had their approvals expanded to include a younger age demographic. Berotralstat was approved in 2020 for Hereditary Angioedema prophylaxis in patients 12 years of age and older1-3. Elapegademase is indicated for use in infants, children, adolescents and adults with ADA deficiency due to SCID; pegademase, an older agent used to manage ADA deficiency in pediatric SCID patients is no longer commercially available1,2,18. C1 esterase inhibitor safety and efficacy have not been determined in pediatric patients younger than 5 years of age, and in 2020 the FDA approval for Haegarda® was expanded to include patients six years of age and older1,2,4-7.

In 2021, agalsidase beta was approved for pediatric use in patients two years of age and older for the treatment of Fabry Disease, and avalglucosidase alfa was approved to treat Pompe Disease in patients one year of age and older1,2,15,17.

Alglucosidase alfa is FDA-approved and has been evaluated for early use to treat Pompe disease in all age groups from neonates to adolescents. In a small study, investigators found that alglucosidase therapy initiated early after diagnosis in neonates less than 1 month of age can improve clinical outcomes even before onset of clinical symptoms in infants with Pompe disease33 .

Maximum recommended dosages for complement inhibitor and protein/enzyme replacement therapies FDA-approved for use in pediatric patients are summarized in Tables 4-6. Dosages exceeding these recommendations will be reviewed.

Table 4. Pediatric Complement Inhibitor Maximum Dosages1-9,12,14
Drug Name Treatment Indication Dosage Form/Strength Maximum Recommended Dosage
berotralstat (Orladeyo®) Hereditary angioedema (HAE) prophylaxis 110 mg, 150 mg oral capsule 12 to 17 years: 150 mg daily
C1 esterase inhibitor, human (Berinert®) HAE treatment 500 unit single-use vial for reconstitution 5 to 17 years: 20 IU/kg by IV injection as a single dose
C1 esterase inhibitor, human (Cinryze®) HAE attacks, routine prevention 500 unit single-use vial for reconstitution
  • 12 to 17 years:
    • 1000 U by IV infusion every 3-4 days+
  • 6 to 11 years:
    • 500 U by IV infusion every 3-4 days+
C1 esterase inhibitor, human (Haegarda®) HAE attacks, routine prevention 2000, 3000 IU single-use vials for reconstitution 6 years and older: 60 IU/kg subcutaneously twice weekly (every 3 to 4 days)
C1 esterase inhibitor, recombinant (Ruconest®) HAE treatment 2100 IU/14 mL single-use vial for reconstitution
  • 13 to 17 years (less than 84 kg):
    • 50 units/kg as single IV dose up to a maximum of 4200 units per dose; may repeat x1 if attack symptoms persist in 24 hour period
  • 13 to 17 years (Greater than 84 kg):
    • 4200 units as a single IV dose; may repeat x1 if attack symptoms persist in 24 hour period
ecallantide (Kalbitor®) HAE treatment 10 mg/ml single-use vials x 3
  • 12 to 17 years:
    • 30 mg subcutaneously as three separate 10 mg injections; may repeat x1 in 24 hour period if attack symptoms persist
eculizumab (Soliris®) Atypical hemolytic uremic syndrome (aHUS) 300 mg/ 30 mL single-dose vial
  • 2 months to 17 years:
    • Greater than or equal to 40 kg:
      • Initial 900 mg IV infusion once weekly for four weeks followed by a 1200 mg IV infusion one week later, maintenance 1200 mg IV infusion over 1-4 hours every two weeks
    • 30-39 kg:
      • Initial 600 mg IV infusion once weekly for two weeks followed by a 900 mg IV infusion one week later, maintenance 900 mg IV infusion over 1-4 hours every two weeks
    • 20-29 kg:
      • Initial 600 mg IV infusion once weekly for three weeks, maintenance 600 mg IV infusion over 1-4 hours every two weeks
  • 10-19 kg:
    • Initial 600 mg IV infusion followed by 300 mg IV infusion one week later, maintenance 300 mg IV infusion over 1-4 hours every two weeks
  • 5-9 kg: Initial 300 mg IV infusion followed by 300 mg IV infusion one week later, maintenance dose of 300 mg IV infusion over 1-4 hours every 3 weeks
lanadelumab-flyo (Takhzyro®) HAE, routine prevention 300 mg/2 mL vial 12 years and older: 300 mg subcutaneously every 2 weeks; every 4-week dosing possible in patients well-controlled for greater than 6 months
ravulizumab (Ultomiris®) aHUS^
Paroxysmal nocturnal hemoglobinuria (PNH)
300 mg/3 mL, 1100 mg/11 mL intravenous solution
  • adolescents greater than or equal to  100 kg:
    • 3600 mg as intravenous infusion every 8 weeks starting 2 weeks after loading dose (loading dose = 3000 mg)
  • adolescents, children 60-99 kg:
    • 3300 mg as intravenous infusion every 8 weeks starting 2 weeks after loading dose (loading dose = 2700 mg)
  • adolescents, children 40-59 kg:
    • 3000 mg as intravenous infusion every 8 weeks starting 2 weeks after loading dose (loading dose = 2400 mg)
  • adolescents, children 30-39 kg:
    • 2700 mg as intravenous infusion every 8 weeks starting 2 weeks after loading dose (loading dose = 1200 mg)
  • children 20-29 kg:
    • 2100 mg as intravenous infusion every 8 weeks starting 2 weeks after loading dose (loading dose = 900 mg)
  • infants, children 10-19 kg:
    • 600 mg as intravenous infusion every 4 weeks starting 2 weeks after loading dose (loading dose = 600 mg)
  • infants, children 5-9 kg:
    • 300 mg as intravenous infusion every 4 weeks starting 2 weeks after loading dose (loading dose = 600 mg)

Legend

  • + in patients 6 to 11 years of age not responding adequately, doses up to 1000 units every 3 or 4 days may be utilized based on individual response. In patients 12 years of age and older not responding adequately, doses up to 2500 units (not exceeding 100 u/kg) every 3 or 4 days may be utilized based on individual patient response
  • ^ treat atypical hemolytic-uremic syndrome with ravulizumab for at least six months
Table 5. Pediatric Enzyme Replacement Therapy Maximum Dosages1,2,15-29,31,32
Drug Name Treatment Indication Dosage Form/Strength Maximum Recommended Dosage 
agalsidase beta (Fabrazyme®) Fabry disease 5 mg, 35 mg single-use vials 2-17 years: 1 mg/kg by intravenous (IV) infusion every 2 weeks
alglucosidase alfa (Lumizyme®) Pompe disease 50 mg single-use vial Birth to any age: 20 mg/kg as IV infusion every 2 weeks
asfotase alfa (Strensiq®) hypophosphatasia (perinatal/infantile- or juvenile-onset) 18 mg/0.45 mL, 28 mg/0.7 mL, 40 mg/1 mL, or 80 mg/0.8 mL single-use vials
  • Hypophosphatasia (perinatal/infantile-onset): 
    • birth to any age: 9 mg/kg weekly as subcutaneous injection as 3 mg/kg three times weekly
  • Hypophosphatasia (juvenile-onset): 
    • 6 years and older: 6 mg/kg weekly as subcutaneous injection, given either as 2 mg/kg three times weekly or 1 mg/kg six times weekly
avalglucosidase alfa (Nexviazyme®) Late onset Pompe disease (lysosomal acid alpha-glucosidase (GAA) deficiency) 100 mg single use vial
  • 1 year of age and older:
    • Greater than or equal to  30 kg: 20 mg/kg as IV infusion every 2 weeks
    • Less than 30 kg: 40 mg/ kg as IV infusion every 2 weeks
cerliponase alfa (Brineura®) late infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease 150 mg/5 ml as 2 single-use vials copackaged with intraventricular electrolytes 3 years and older: 300 mg every other week by intraventricular infusion, followed by intraventricular electrolytes
elapegademase (Revcovi®) Adenosine deaminase severe combined immunodeficiency 2.4 mg/1.5 mL intramuscular solution
  • treatment naïve:
    • 0.2 mg/kg as intramuscular injection twice weekly for a minimum of 12 to 24 weeks; titrate up by 0.033 mg/kg/week to maintain ADA trough greater than 30 mmol/hr/L, trough deoxyadenosine nucleotides less than 0.02 mmol/L, and maintain immune reconstitution
  • patients transitioning from pegademase:
    • Patients receiving pegademase doses less than or equal to 30 U/kg should receive elapegademase 0.2 mg/kg intramuscularly once weekly; patients with pegademase doses Greater than 30 U/kg should receive equivalent elapegademase dose*
elosulfase (Vimizim®) Mucopolysaccharidoses (MPS) IVA (Morquio A syndrome) 5 mg/5 mL single-use vial 5 years and older: 2 mg/kg by IV infusion over a minimum of 3.5-4.5 hours once weekly
galsulfase (Naglazyme®) MPS VI (Maroteaux-Lamy syndrome) 5 mg/5 mL preservative-free vials 3 months and older: 1 mg/kg by IV infusion once weekly
idursulfase (Elaprase®) MPS II (Hunter syndrome) 6 mg/3 mL single-use vial 16 months to 17 years: 0.5 mg/kg as IV infusion once weekly
imiglucerase (Cerezyme®) Gaucher disease, type 1 (nonneuropathic) 400 mg vials for reconstitution 2 to 16 years: 60 U/kg by IV infusion over 1-2 hours every 2 weeks
imiglucerase (Cerezyme®) Gaucher disease, type 1 (nonneuropathic) 400 mg vials for reconstitution 2 to 16 years: 60 U/kg by IV infusion over 1-2 hours every 2 weeks
laronidase (Aldurazyme®) MPS 1 (Hurler, Hurler-Scheie forms; Scheie form with moderate to severe symptoms) 2.9 mg/5 mL single-use vials 6 months of age and older: 0.58 mg/kg by IV infusion over 3-4 hours once weekly
sacrosidase (Sucraid®) Congenital sucrase-isomaltase deficiency (CSID) 8500 international units/mL as 118 mL oral solution bottles, 8500 units/ mL as 2 mL oral solution
  • 5 months to 17 years:
    • less than or equal to 15 kg:
      • 8500 units orally mixed in 2-4 ounces of water, milk, or infant formula with each meal or snack
    • Greater than 15 kg:
      • 7,000 units orally mixed in 2-4 ounces of water or milk with each meal or snack
sebelipase alfa (Kanuma®) Wolman Disease (Lysosomal acid lipase (LAL) deficiency) 20 mg/10 mL single-use vial Greater than or equal to  1 month of age to 17 years: 3 mg/kg by IV infusion once every other week
  Wolman Disease (Rapidly progressive LAL deficiency developing in first 6 months of life)   1-12 months of age: 5 mg/kg by IV infusion once weekly
taliglucerase alfa (Elelyso®) Gaucher disease, type 1 200 unit single-use vials for reconstitution    treatment-naïve (4 years and older): 60 U/kg by IV infusion once every 2 weeks previously treated with imiglucerase (4 years and older): use same unit/kg dosage for taliglucerase that was prescribed for imiglucerase and administer every two weeks
velaglucerase alfa (Vpriv®) Gaucher disease, type 1 400 unit single-use vials for reconstitution    treatment-naïve (4 years and older): 60 U/kg by IV infusion once every 2 weeks previously treated with imiglucerase (4 years and older): use same unit/kg dosage for velaglucerase that was prescribed for imiglucerase and administer every two weeks
vestronidase alfa-vjbk (Mepsevii®) MPS VII (Sly syndrome), excluding central nervous system symptoms 10 mg/5 mL single-use vial birth to 17 years: 4 mg/kg as IV infusion every two weeks

Legend

  • * elapegademase equivalent dose to pegademase: pegademase dose (U/kg) divided by 150
Table 6. Pediatric Protein Replacement Therapy Maximum Dosages1,2,32
Drug Name Treatment Indication Dosage Form/Strength Maximum Recommended Dosage
protein C concentrate (Ceprotin®) Severe congenital protein C deficiency (acute episode) 500 IU, 1000 IU single-use vial for reconstitution birth to 17 years:  100-120 IU/kg initial dose by IV infusion, followed by 60-80 IU/kg every 6 hours for 3 doses by IV infusion*
  Severe congenital protein C deficiency (short-term prophylaxis/ maintenance dose)   birth to 17 years:  45-60 IU/kg every 6 to 12 hours by IV infusion*
  Severe congenital protein C deficiency (long-term prophylaxis)   birth to 17 years:  45-60 IU/kg every 12 hours by IV infusion*

Legend

  • * maximum protein C concentrate infusion rate: 2 ml/min, except in children less than 10 kg, where infusion rate should not exceed 0.2 ml/kg/min