Complement Inhibitor and Enzyme/Protein Replacement Therapy

Last Updated

Medications listed in the tables and non-FDA approved indications included in these retrospective criteria are not indicative of Texas Vendor Drug Program formulary coverage.

  • Revision history
    • April 2022; March 2020; March 2018; March 2017; April 2015; March 2015; Feb. 2013. 
  • Initially developed
    • Dec. 2012

1. Dosage

  • Adenosine deaminase (ADA) deficiency in severe combined immunodeficiency (SCID)
  • Atypical hemolytic uremic syndrome (aHUS) 
  • Congenital sucrase isomaltase deficiency (CSID)
  • Fabry disease
  • Gaucher disease 
  • Hereditary angioedema (HAE)
  • Hypophosphatasia
  • Wolman disease (lysosomal acid lipase (LAL) deficiency)
  • Mucopolysaccharidoses (MPS) 
    • Hurler and Hurler-Scheie forms of MPS I; 
    • Hunter syndrome (MPS II); 
    • Morquio A syndrome (MPS IVA);
    • Maroteaux-Lamy syndrome (MPS VI);
    • Sly syndrome (MPS VII)
  • Myasthenia gravis
  • Neuromyelitis optica spectrum disorder
  • Paroxysmal nocturnal hemoglobinuria
  • Pompe disease
  • Severe congenital protein C deficiency

1.1. Adults

Recommended doses for complement inhibitor as well as enzyme/protein replacement therapy FDA-approved for use in adults are summarized in Tables 1-3.  Patient profiles containing doses exceeding maximum recommendations will be reviewed.

Table 1. Adult Complement Inhibitor Maximum Dosages1-14
Drug Name Treatment Indication Dosage Form/Strength Maximum Recommended Dosage 
Berotralstat (Orladeyo®) Hereditary angioedema (HAE) prophylaxis 110 mg, 150 mg oral capsule 150 mg by mouth daily*
C1 esterase inhibitor, human (Berinert®) HAE treatment 500 international unit (IU) single-use vial for reconstitution 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 1000 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 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
  • Greater than or equal to  84 kg:
    • 4200 units as a single IV dose; may repeat x1 if attack symptoms persist in 24-hour period
  • 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
Ecallantide (Kalbitor®) HAE treatment 10 mg/ml single-use vials x 3 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 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 thereafter 
  Myasthenia gravis, generalized   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
  Neuromyelitis optica spectrum disorder   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
  Paroxysmal nocturnal hemoglobinuria (PNH)   Initial 600 mg IV infusion once weekly for four weeks followed by a 900 mg IV infusion one week later, maintenance 900 mg IV infusion over 1-4 hours every two weeks thereafter
icatibant acetate (Firazyr®, Sajazir®) HAE treatment 30 mg/3 mL prefilled syringe, 30 mg/ 3 mL solution for injection 30 mg subcutaneously as single dose; may repeat x2 with 6 hours between doses in 24-hour period if attack symptoms persist (maximum 3 doses per 24-hour period) 
lanadelumab-flyo (Takhzyro®) HAE, routine prevention 300 mg/2 mL vial 300 mg subcutaneously every 2 weeks; every 4-week dosing possible in patients well-controlled for Greater than 6 months
pegcetacoplan (Empaveli®) PNH 1080 mg/ 20 mL solution for injection 1080 mg subcutaneously twice weekly
ravulizumab (Ultomiris®) aHUS^
PNH
300 mg/3 mL, 100 mg/11 mL intravenous solution in single-dose vial
  • 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)
  • 60-99 kg:
    • 3300 mg as intravenous infusion every 8 weeks starting 2 weeks after loading dose (loading dose = 2700 mg)
  • 40-59 kg:
    • 3000 mg as intravenous infusion every 8 weeks starting 2 weeks after loading dose (loading dose = 2400 mg)
  • 30-39 kg:
    • 2700 mg as intravenous infusion every 8 weeks starting 2 weeks after loading dose (loading dose = 1200 mg)
  • 20-29 kg:
    • 2100 mg as intravenous infusion every 8 weeks starting 2 weeks after loading dose (loading dose = 900 mg)
  • 10-19 kg:
    • 600 mg as intravenous infusion every 4 weeks starting 2 weeks after loading dose (loading dose = 600 mg)
  • 5-9 kg:
    • 300 mg as intravenous infusion every 4 weeks starting 2 weeks after loading dose (loading dose = 600 mg)

Legend

  • * Berotralstat is dosed at 110 mg by mouth daily in patients with moderate to severe hepatic impairment, chronic use of P-glycoprotein (P-gp) or BCRP (breast cancer resistance protein) inhibitors, or patients with persistent gastrointestinal (GI) reactions 
  • + in patients 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 2. Adult Enzyme Replacement Therapy Maximum Dosages1,2,15-29
Drug Name Treatment Indication Dosage Form/Strength Maximum Recommended Dosage
agalsidase beta (Fabrazyme®) Fabry disease 5 mg, 35 mg single-use vials 1 mg/kg by intravenous (IV) infusion every 2 weeks
alglucosidase alfa (Lumizyme®) Pompe disease (lysosomal acid alpha-glucosidase (GAA) deficiency) 50 mg single-use vial 20 mg/kg as IV infusion every 2 weeks
Avalglucosidase alfa (Nexviazyme®) Late onset Pompe disease (lysosomal acid alpha-glucosidase (GAA) deficiency) 100 mg single use vial
  • 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
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 alfa (Vimizim®) Mucopoly-saccharidosis (MPS) IVA (Morquio A syndrome) 5 mg/5 mL single-use vial 2 mg/kg by IV infusion once weekly
galsulfase (Naglazyme®) MPS VI (Maroteaux-Lamy syndrome) 5 mg/5 mL preservative-free vials 1 mg/kg by IV infusion once weekly
idursulfase (Elaprase®) MPS II (Hunter syndrome) 6 mg/3 mL single-use vial 0.5 mg/kg as IV infusion once weekly
imiglucerase (Cerezyme®) Gaucher disease, type 1 (non-neuropathic) 400 mg vials for reconstitution 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 0.58 mg/kg by IV infusion once weekly
migalastat (Galafold®) Fabry disease with amenable galactosidase alpha gene (GLA) variant 123 mg oral capsule 123 mg by mouth every other day
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 Greater than 15 kg: 17,000 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 3 mg/kg by IV infusion once every other week
taliglucerase alfa (Elelyso®) Gaucher disease, type 1 200 unit single-use vials for reconstitution
  • treatment-naïve:
    • 60 U/kg by IV infusion once every 2 weeks
  • previously treated with imiglucerase:
    • 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:
    • 60 U/kg as IV infusion every 2 weeks
  • previously treated with imiglucerase:
    • 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 4 mg/kg as IV infusion every two weeks

Legend

  • * elapegademase equivalent dose to pegademase: pegademase dose (U/kg) divided by 150
Table 3. Adult Protein Replacement Therapy Maximum Dosages1,2,30
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 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*)   45-60 IU/kg every 6 to 12 hours by IV infusion
  Severe congenital protein C deficiency (long-term prophylaxis*)   45-60 IU/kg every 12 hours by IV infusion

Legend

  • * maximum protein C concentrate infusion rate: 2 ml/min

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

2. Duration of Therapy

There is no basis for limiting the duration of complement inhibitor and enzyme/protein replacement therapy as enzyme deficiencies represent chronic disorders and require sustained treatment1-32.

3. Duplicative Therapy

FDA-approved enzyme replacement therapies are indicated for specific enzyme deficiencies. Patients with multiple enzyme deficiencies may be prescribed multiple enzyme replacement therapies concurrently. Adjunctive administration of enzyme replacement therapies without multiple enzyme deficiency diagnoses is not clinically reasonable and will be evaluated.

4. References

  1. IBM Micromedex® DRUGDEX® (electronic version). IBM Watson Health, Greenwood Village, Colorado, USA. Available at: https://www-micromedexsolutions-com.libproxy.uthscsa.edu/ (cited: March 9, 2022).
  2. Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.; 2022. Available at: http://www.clinicalpharmacology-ip.com.ezproxy.lib.utexas.edu/. Accessed March 9, 2022.
  3. Berotralstat oral capsules (Orladeyo®) package insert. BioCryst Pharmaceuticals, Inc., December 2020.
  4. C1 esterase inhibitor, human (Berinert®) package insert. CSL Behring, September 2021.
  5. C1 esterase inhibitor, human intravenous injection (Cinryze®) package insert. ViroPharma Biologics LLC, January 2021.
  6. C1 esterase inhibitor subcutaneous injection (Haegarda®) package insert. CSL Behring, October 2020.
  7. C1 esterase inhibitor, recombinant (Ruconest®) package insert.  Pharming Healthcare Inc., April 2020.
  8. Ecallantide subcutaneous injection (Kalbitor®) package insert. Takeda Pharmaceuticals America, Inc., November 2021.
  9. Eculizumab intravenous injection (Soliris®) package insert. Alexion Pharmaceuticals, Inc., April 2021.
  10. Icatibant subcutaneous injection (Firazyr®) package insert. Takeda Pharmaceuticals America, Inc., September 2020.
  11. Icatibant subcutaneous injection (Sajazir®) package insert. Cycle Pharmaceuticals LTD., June 2021.
  12. Lanadelumab subcutaneous injection (Takhzyro®) package insert. Takeda Pharmaceuticals America, Inc., February 2022.
  13. Pegcetacoplan subcutaneous solution (Empaveli®) package insert. Apellis Pharmaceuticals, Inc., August 2021.
  14. Ravulizumab intravenous injection (Ultomiris®) package insert. Alexion Pharmaceuticals, Inc., January 2022.
  15. Agalsidase beta injection (Fabrazyme®) package insert. Genzyme Corporation, August 2021.
  16. Alglucosidase alfa injection (Lumizyme®) package insert. Genzyme Corporation, July 2021.
  17. Avalglucosidase alfa intravenous injection (Nexviazyme®) package insert. Genzyme Corporation, August 2021.
  18. Elapegademase intramuscular injection (Revcovi®) package insert. Leadiant Biosciences, November 2021.
  19. Elosulfase injection (Vimizim®) package insert. BioMarin Pharmaceutical Inc., January 2021.
  20. Galsulfase injection (Naglazyme®) package insert. BioMarin Pharmaceutical Inc., April 2020.
  21. Idursulfase injection (Elaprase®) package insert. Shire Human Genetic Therapies, Inc., October 2021.
  22. Imiglucerase injection (Cerezyme®) package insert. Genzyme Corporation, January 2022.
  23. Laronidase intravenous infusion (Aldurazyme®) package insert.  Genzyme Corporation, December 2019.
  24. Migalastat oral capsules (Galafold®) package insert. Amicus Therapeutics US, LLC, December 2021.
  25. Sacrosidase oral solution (Sucraid®) package insert. QOL Medical, LLC, August 2021.
  26. Sebelipase injection (Kanuma®) package insert. Alexion Pharmaceuticals, Inc., November 2021. 
  27. Taliglucerase alfa injection (Elelyso®) package insert. Pfizer, July 2021.
  28. Velaglucerase alfa injection (Vpriv®) package insert. Takeda Pharmaceuticals America, Inc., October 2021.
  29. Vestronidase alfa-vjbk injection (Mepsevii®) package insert. Ultragenyx Pharmaceutical Inc., December 2020.
  30. Protein C concentrate (Ceprotin®) package insert. Baxalta US Inc., September 2021.
  31. Asfotase alfa injection (Strensiq®) package insert. Alexion Pharmaceuticals, Inc., April 2021.
  32. Cerliponase alfa injection (Brineura®) package insert. BioMarin Pharmaceutical Inc., July 2020.
  33. Ramaswami U, Parini R, Kampmann C, Beck M. Safety of agalsidase alfa in patients with Fabry disease under 7 years. Acta Paediatrica. 2011;100(4):605-11.