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. Ivacaftor is not recommended for use concurrently with strong CYP3A inducers. Concomitant use decreases exposure of ivacaftor and may decrease effectiveness1-5. Dosages in patient profiles exceeding these recommendations will be reviewed.
| Drug Name | Treatment Indication | Dosage Form/Strength | Maximum Recommended Dosage |
|---|---|---|---|
| ivacaftor (Kalydeco) | CF (patients with one mutation in CFTR gene responsive to ivacaftor) | 150 mg oral tablets | 150 mg orally every 12 hours with fat-containing food |
Legend:
- CF = cystic fibrosis
- CFTR = cystic fibrosis transmembrane conductance regulator
| Drug Name | Treatment Indication | Dosage Form/Strength | Maximum Recommended Dosage |
|---|---|---|---|
| lumacaftor/ivacaftor (Orkambi) | CF (patients homozygous for F508del mutation in the CFTR gene) | 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 |
| tezacaftor/ivacaftor (Symdeko) | CF (patients homozygous for F508del mutation or have at least one mutation in the CFTR gene responsive to tezacaftor/ivacaftor) | tezacaftor 100 mg/ivacaftor 150 mg co-packaged with 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 |
| elexacaftor/tezacaftor/ivacaftor (Trikafta) | 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 100 mg/ tezacaftor 50 mg/ ivacaftor 75 mg oral tablet co-packaged with 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 100 mg/ivacaftor 150 mg once daily in morning Days 2 and 3: no dosages administered Day 4: tezacaftor 100 mg/ivacaftor 150 mg 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 100 mg/ivacaftor 150 mg once daily in morning ay 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