1.1. Adults
Recommended adult ivacaftor doses as monotherapy and combination therapy are summarized in Tables 4 and 5. Dosage adjustments for ivacaftor monotherapy and combination therapy when administered adjunctively with cytochrome P450 3A4 inhibitors are summarized in Table 6 1-3, 4, 6, 7, 10. Dosages in patient profiles exceeding these recommendations will be reviewed.
| Treatment Indication | Drug Name | Dosage Form/Strength | Maximum Recommended Dosage |
|---|---|---|---|
| CF (patients with one mutation in CFTR gene responsive to ivacaftor potentiation) | ivacaftor (Kalydeco®) | 150 mg oral tablets | 150 mg orally every 12 hours with fat-containing food |
Legend:
- CF = cystic fibrosis
- CFTR = cystic fibrosis transmembrane conductance regulator
| Treatment Indication | Drug Name | Dosage Form/Strength | Maximum Recommended Dosage |
|---|---|---|---|
| CF (patients homozygous for F508del mutation in the CFTR gene) | lumacaftor/ivacaftor (Orkambi®) | 200 mg/125 mg oral tablets | 400 mg/250 mg (2 x 200 mg lumacaftor/125 mg ivacaftor tablets) orally 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 100 mg/ivacaftor 150 mg; ivacaftor 150 mg oral tablets | tezacaftor 100 mg/ivacaftor 150 mg in morning and ivacaftor 150 mg in evening approximately 12 hours apart with fat-containing food |
| CF (patients have at least one F508del mutation in the CFTR gene or have at least one mutation in the CFTR gene responsive to elexacaftor/tezacaftor/ivacaftor) |
elexacaftor/tezacaftor/ivacaftor (Trikafta®) | elexacaftor 100 mg/ tezacaftor 50 mg/ ivacaftor 75 mg oral tablet; ivacaftor 150 mg oral tablet | 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 |
Legend:
- CF = cystic fibrosis
- CFTR = cystic fibrosis transmembrane conductance regulator
| Ivacaftor Drug Name | Concurrent CYP3A4 Inhibitor Therapy | Dosage Recommendations* |
|---|---|---|
| ivacaftor (Kalydeco®) | strong CYP3A inhibitors (e.g., ketoconazole) | ivacaftor dosages should be reduced to 150 mg twice weekly |
| ivacaftor (Kalydeco®) | moderate CYP3A inhibitors (e.g., erythromycin, fluconazole) | ivacaftor dosages should be reduced to 150 mg once daily |
| lumacaftor/ivacaftor (Orkambi®) | strong CYP3A inhibitors (e.g., ketoconazole) | lumacaftor/ivacaftor dosages should be reduced to 200 mg/125 mg once daily in patients receiving strong CYP3A inhibitors for the first week, followed by 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 |
| lumacaftor/ivacaftor (Orkambi®) | moderate CYP3A inhibitors (e.g., erythromycin, fluconazole) | no dosage adjustments recommended |
| tezacaftor/ivacaftor (Symdeko®) | strong CYP3A inhibitors (e.g., ketoconazole) |
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 |
| tezacaftor/ivacaftor (Symdeko®) | moderate CYP3A inhibitors (e.g., erythromycin, fluconazole) |
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 |
| elexacaftor/tezacaftor/ivacaftor (Trikafta®) | strong CYP3A inhibitors (e.g., ketoconazole) |
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) |
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/3A4 = cytochrome P450 3A/3A4
- *all dosages should be given with a fat-containing meal