1.2. Pediatrics

Tables 7 and 8 summarize ivacaftor dosing recommendations as monotherapy and combination therapy for pediatric patients. Ivacaftor is not recommended in patients less than 4 months of age1-4. Safety and efficacy of lumacaftor/ivacaftor combination therapy in children less than 2 years of age have not been established1-3, 6. Tezacaftor/ivacaftor safety and efficacy have not been determined in children below 6 years of age, while elexacaftor/tezacaftor/ivacaftor efficacy/safety have not been established in children younger than 6 years of age1-3, 7, 10. Dosage adjustments for ivacaftor monotherapy and combination therapy when administered concomitantly with cytochrome P450 3A4 inhibitors are summarized in Table 9. Ivacaftor is not recommended for use concurrently with CYP3A strong inducers.

Table 7. Maximum Recommended Pediatric Ivacaftor Dosages: Monotherapy1-4
Treatment Indication Drug Name Dosage Form/Strength Maximum Recommended Dosage
CF (patients with one mutation in CFTR gene responsive to ivacaftor potentiation) ivacaftor (Kalydeco®)

25 mg, 50 mg, 75 mg oral granules

150 mg oral tablets

children/adolescents 6-17 years: 150 mg orally every 12 hours with fat-containing food

infants/children 6 months to less than 6 years (greater than 14 kg): 75 mg as oral granules every 12 hours with fat-containing food

infants/children 6 months to less than 6 years (7 kg to less than 14 kg): 50 mg as oral granules every 12 hours with fat-containing food

infants/children 6 months to less than 6 years (5 kg to less than 7 kg): 25 mg as oral granules every 12 hours with fat-containing food

infants 4 to 5 months weighing 5 kg or more: 25 mg as oral granules every 12 hours with fat-containing food

Legend:

  • CF = cystic fibrosis
  • CFTR = cystic fibrosis transmembrane conductance regulator
Table 8. Maximum Recommended Pediatric Ivacaftor Dosages: Combination Therapy1-3, 6, 7, 10
Treatment Indication Drug Name Dosage Form/Strength Maximum Recommended Dosage 
CF (patients homozygous for F508del mutation in the CFTR gene) lumacaftor/ivacaftor (Orkambi®)

100 mg/ 125 mg, 150 mg/188 mg oral granules

100 mg/125 mg, 200 mg/125 mg oral tablets
  • children/adolescents 12 years and older:
    • 400 mg/250 mg (2 x 200 mg lumacaftor/125 mg ivacaftor tablets) orally every 12 hours with fat-containing food
  • children 6-11 years:
    • 200 mg/250 mg (2 x 100 mg lumacaftor/125 mg ivacaftor tablets) orally every 12 hours with fat-containing food
  • children 2-5 years (greater than 14 kg):
    • 150 mg/188 mg oral granules every 12 hours with fat-containing food
  • children 2-5 years (less than 14 kg):
    • 100 mg/125 mg oral granules every 12 hours with fat-containing food
CF (patients homozygous for F508del mutation or have at least one mutation in the CFTR gene responsive to tezacaftor/ivacaftor) tezacaftor/ivacaftor (Symdeko®)

tezacaftor 50 mg/ivacaftor 75 mg oral tablet; ivacaftor 75 mg oral tablet

tezacaftor 100 mg/ivacaftor 150 mg oral tablet; ivacaftor 150 mg oral tablet
  • children/adolescents 12-17 years:
    • tezacaftor 100 mg/ivacaftor 150 mg in morning and ivacaftor 150 mg in evening approximately 12 hours apart with fat-containing food
  • children 6-11 years (greater than 30 kg):
    • tezacaftor 100 mg/ ivacaftor 150 mg in morning and ivacaftor 150 mg in evening approximately 12 hours apart with fat-containing food
  • children 6-11 years (less than 30 kg):
    • tezacaftor 50 mg/ ivacaftor 75 mg in morning and ivacaftor 75 mg in evening approximately 12 hours apart with fat-containing food
CF (patients have at least one F508del mutation in the CFTR gene) elexacaftor/tezacaftor/ivacaftor (Trikafta®)

elexacaftor 100 mg/ tezacaftor 50 mg/ ivacaftor 75 mg oral tablet; ivacaftor 150 mg oral tablet

elexacaftor 50 mg/ tezacaftor 25 mg/ ivacaftor 37.5 mg oral tablet; ivacaftor 75 mg oral tablet
  • children/adolescents 12-17 years:
    • 2 tablets (elexacaftor 100 mg/ tezacaftor 50 mg/ ivacaftor 75 mg) in morning and one ivacaftor 150 mg tablet in evening approximately 12 hours apart with fat-containing food
  • children 6-11 years greater than or equal to 30 kg):
    • 2 tablets (elexacaftor 100 mg/ tezacaftor 50 mg/ ivacaftor 75 mg) in the morning and one ivacaftor 150 mg tablet in the evening approximately 12 hours apart with fat-containing food
  • children 6-11 years (less than 30 kg):
    • 2 tablets (elexacaftor 50 mg/ tezacaftor 25 mg/ ivacaftor 37.5 mg) in the morning and one ivacaftor 75 mg tablet in the evening approximately 12 hours apart with fat-containing food

 Legend:

  • CF = cystic fibrosis
  • CFTR = cystic fibrosis transmembrane conductance regulator
Table 9. Ivacaftor Pediatric Dosage Adjustments with Concurrent CYP3A4 Inhibitor Therapy
Ivacaftor Drug Name Concurrent CYP3A4 Inhibitor Therapy Dosage Recommendations*
ivacaftor (Kalydeco®) strong CYP3A inhibitors (e.g., ketoconazole)
  • greater than 6 years of age:
    • 150 mg twice weekly
  • 6 months to less than 6 years of age:
    • greater than 14 kg:
      • 75 mg granule packet twice weekly
  • 7 to less than 14 kg:
    • 50 mg granule packet twice weekly
  • 5 to less than 7 kg:
    • 25 mg granule packet twice weekly
  • 4 months to less than 6 months of age:
    • Use not recommended
ivacaftor (Kalydeco®) moderate CYP3A inhibitors (e.g., erythromycin, fluconazole)
  • greater than 6 years of age:
    • 150 mg orally once daily
  • 6 months to less than 6 years of age:
    • greater than 14 kg:
      • 75 mg granule packet orally once daily
  • 7 to less than 14 kg:
    • 50 mg granule packet orally once daily
  • 5 to less than 7 kg:
    • 25 mg granule packet orally once daily
  • 4 months to less than 6 months of age:
    • Use not recommended
lumacaftor/ivacaftor (Orkambi®) strong CYP3A inhibitors (e.g., ketoconazole)
  • greater than or equal to 12 years:
    • lumacaftor/ivacaftor dosages should be reduced to 200 mg/125 mg once daily for the first week, followed by 2 tablets (lumacaftor 400 mg/ivacaftor 250 mg) every 12 hours thereafter; no dosage adjustments are needed if CYP3A inhibitors are initiated in patients already taking lumacaftor/ivacaftor
  • 6 to 11 years:
    • lumacaftor/ivacaftor dosages should be reduced to 100 mg/125 mg once daily for the first week, followed by 2 tablets (lumacaftor 200 mg/ivacaftor 250 mg) every 12 hours thereafter; no dosage adjustments are needed if CYP3A inhibitors are initiated in patients already taking lumacaftor/ivacaftor
lumacaftor/ivacaftor (Orkambi®) strong CYP3A inhibitors (e.g., ketoconazole)
  • 2 to 5 years (greater than or equal to 14 kg):
    • lumacaftor/ivacaftor dosages should be reduced to 1 granule packet (150 mg/188 mg) every other day for the first week, followed by 1 granule packet (lumacaftor 150 mg/ivacaftor 188 mg) every 12 hours thereafter; no dosage adjustments are needed if CYP3A inhibitors are initiated in patients already taking lumacaftor/ivacaftor
  • 2 to 5 years (less than 14 kg):
    • lumacaftor/ivacaftor dosages should be reduced to 1 granule packet (100 mg/125 mg) every other day for the first week, followed by 1 granule packet (lumacaftor 100 mg/ivacaftor 125 mg) every 12 hours thereafter; no dosage adjustments are needed if CYP3A inhibitors are initiated in patients already taking lumacaftor/ivacaftor
lumacaftor/ivacaftor (Orkambi®) moderate CYP3A inhibitors (e.g., erythromycin, fluconazole) no dosage adjustments recommended
tezacaftor/ivacaftor (Symdeko®) strong CYP3A inhibitors (e.g., ketoconazole)
  • greater than or equal to 6 years to less than 12 years greater than or equal to 30 kg;
    • children/ adolescents greater than or equal to 12 years:
      • Day 1: tezacaftor/ivacaftor 100 mg/150 once daily in morning
      • Days 2 and 3: no dosages administered
      • Day 4: tezacaftor/ivacaftor 100 mg/150 once daily in morning 
    • The evening ivacaftor dose should NOT be given
  • Continue twice weekly (morning) administration schedule, with 3-4 days between dosages
  • Greater than or equal to 6 years to less than 12 years less than 30 kg:
    • Day 1: tezacaftor/ivacaftor 50 mg/75 once daily in morning
    • Days 2 and 3: no dosages administered
    • Day 4: tezacaftor/ivacaftor 50 mg/75 once daily in morning 
    • The evening ivacaftor dose should NOT be given
  • Continue twice weekly (morning) administration schedule, with 3-4 days between dosages
tezacaftor/ivacaftor (Symdeko®) moderate CYP3A inhibitors (e.g., erythromycin, fluconazole)
  • greater than or equal to 6 years to less than 12 years
    • Greater than or equal to 30 kg;
    • children/adolescents greater than or equal to 12 years:
      • Day 1: tezacaftor/ivacaftor 100 mg/150 once daily in morning
      • Day 2: ivacaftor 150 mg once daily in morning
      • The evening ivacaftor dose should NOT be given
      • Continue alternate day (morning) administration schedule
  • Greater than or equal to 6 years to less than 12 years
    • Less than 30 kg:
      • Day 1: tezacaftor/ivacaftor 50 mg/75 once daily in morning
      • Day 2:  ivacaftor 75 mg once daily in morning
  • The evening ivacaftor dose should NOT be given
  • Continue alternate day (morning) administration schedule
elexacaftor/tezacaftor/ivacaftor (Trikafta®) strong CYP3A inhibitors (e.g., ketoconazole)
  • 6-11 years of age: 
    • Weight less than 30 kg:
      • 2 tablets (elexacaftor 50 mg/ tezacaftor 25 mg/ ivacaftor 37.5 mg) in morning twice weekly, with 3-4 days between doses
    • The evening ivacaftor dose should NOT be given
  • 6-11 years of age:
    • Weight greater than or equal to 30 kg:
      • 2 tablets (elexacaftor 100 mg/ tezacaftor 50 mg/ ivacaftor 75 mg) in morning twice weekly, with 3-4 days between doses 
    • The evening ivacaftor dose should NOT be given
  • Greater than or equal to 12 years of age: 
    • 2 tablets (elexacaftor 100 mg/ tezacaftor 50 mg/ ivacaftor 75 mg) in morning twice weekly, with 3-4 days between dosages
    • The evening ivacaftor dose should NOT be given
elexacaftor/tezacaftor/ivacaftor (Trikafta®) moderate CYP3A inhibitors (e.g., erythromycin, fluconazole)
  • 6-11 years of age:
    • Weight less than 30 kg:
      • Day 1: 2 tablets (elexacaftor 50 mg/ tezacaftor 25 mg/ ivacaftor 37.5 mg) in morning
      • Day 2: ivacaftor 75 mg once daily in morning
    • The evening ivacaftor dose should NOT be given
    • Continue alternate day (morning) administration schedule
  • 6-11 years of age:
    • Weight greater than or equal to 30 kg:
      • Day 1: 2 tablets (elexacaftor 100 mg/ tezacaftor 50 mg/ ivacaftor 75 mg) in morning
      • Day 2: ivacaftor 75 mg once daily in morning
    • The evening ivacaftor dose should NOT be given
    • Continue alternate day (morning) administration schedule
  • Greater than or equal to 12 years of age:
    • Day 1: 2 tablets (elexacaftor 100 mg/ tezacaftor 50 mg/ ivacaftor 75 mg) in morning
    • Day 2: ivacaftor 150 mg once daily in morning
    • The evening ivacaftor dose should NOT be given
    • Continue alternate day (morning) administration schedule

Legend:

  • CYP3A = cytochrome P450 3A