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.
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 |
|
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 |
|
ecallantide (Kalbitor®) | HAE treatment | 10 mg/ml single-use vials x 3 |
|
eculizumab (Soliris®) | Atypical hemolytic uremic syndrome (aHUS) | 300 mg/ 30 mL single-dose vial |
|
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 |
|
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
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 |
|
avalglucosidase alfa (Nexviazyme®) | Late onset Pompe disease (lysosomal acid alpha-glucosidase (GAA) deficiency) | 100 mg single use vial |
|
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 |
|
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 |
|
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
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