Inborn errors of metabolism:
Indications for KALYDECO:
Treatment of cystic fibrosis (CF) in patients ≥4mos who have one mutation in the CFTR gene that is responsive to ivacaftor potentiation based on clinical and/or in vitro assay data.
Adults and Children:
<4mos, 4–<6mos (with hepatic impairment and/or on concomitant moderate or strong CYP3A inhibitors): not recommended. Oral granules should be mixed with 1 tsp (5mL) of soft-food or liquid (eg, yogurt, applesauce, milk, or juice) and completely consumed. Take with fat-containing food (eg, eggs, butter, peanut butter, cheese pizza, dairy products). 4–<6mos (≥5kg): 25mg packet every 12hrs. 6mos–<6yrs (5–<7kg): 25mg packet every 12hrs; (7–<14kg): 50mg packet every 12hrs; (≥14kg): 75mg packet every 12hrs. ≥6yrs: 150mg tab every 12hrs. Concomitant CYP3A inhibitors (≥6mos): reduce to twice weekly (strong inhibitors) or once daily (moderate inhibitors). Hepatic impairment (≥6mos): reduce to once daily for moderate impairment, once daily or less frequently if severe.
If genotype is unknown, use an FDA-cleared CF mutation test to detect the presence of a CFTR mutation followed by verification with bi-directional sequencing when recommended by the mutation test instructions. Assess ALT/AST levels prior to initiating therapy, every 3 months during the first year of treatment, and annually thereafter. History of ALT/AST elevations: monitor LFTs more frequently. If increased ALT/AST levels develop, monitor closely until abnormalities resolved. Interrupt dosing if ALT/AST is >5xULN; after resolution, consider restarting. Perform baseline and follow-up eye exams. Hepatic impairment. Severe renal impairment or ESRD. Pregnancy. Nursing mothers.
Cystic fibrosis transmembrane conductance regulator (CFTR) potentiator.
Potentiated by strong CYP3A inhibitors (eg, ketoconazole, itraconazole, posaconazole, voriconazole, telithromycin, clarithromycin) and moderate CYP3A inhibitors (eg, fluconazole, erythromycin); see Adults and Children. May be potentiated by grapefruit and Seville oranges; avoid. Antagonized by strong CYP3A inducers (eg, rifampin, rifabutin, phenobarbital, carbamazepine, phenytoin, St. John’s Wort); use not recommended. Potentiates CYP3A and/or P-gp substrates (eg, digoxin, cyclosporine, tacrolimus); monitor.
Headache, oropharyngeal pain, upper respiratory tract infection, nasal congestion, abdominal pain, nasopharyngitis, diarrhea, rash, nausea, dizziness; non-congenital lens opacities/cataracts.
Generic Drug Availability:
Tabs—56, 60; Oral granules—56