Inborn errors of metabolism:
Indications for: TRIKAFTA
Cystic fibrosis (CF) in patients ≥6yrs who have at least one F508del mutation in the CFTR gene or a mutation in the CFTR gene that is responsive based on in vitro data.
Swallow whole. Take with fat-containing food (eg, eggs, cheeses, nuts, whole milk, meats). ≥12yrs: 2 tabs (100mg/50mg/75mg) in the AM and 1 tab (ivacaftor 150mg) in the PM, approx. 12hrs apart. Moderate hepatic impairment (not recommended; if needed, use with caution at reduced dose), concomitant moderate or strong CYP3A inhibitors: see full labeling.
<6yrs: not established. Swallow whole. Take with fat-containing food (eg, eggs, cheeses, nuts, whole milk, meats). 6–<12yrs (<30kg): 2 tabs (50mg/25mg/37.5mg) in the AM and 1 tab (ivacaftor 75mg) in the PM, approx. 12hrs apart; (≥30kg): 2 tabs (100mg/50mg/75mg) in the AM and 1 tab (ivacaftor 150mg) in the PM, approx. 12hrs apart. Moderate hepatic impairment (not recommended; if needed, use with caution at reduced dose), concomitant moderate or strong CYP3A inhibitors: see full labeling.
If genotype is unknown, use an FDA-cleared CF mutation test to confirm the presence of at least 1 F508del mutation. Pre-existing advanced liver disease (eg, cirrhosis, portal hypertension, ascites, hepatic encephalopathy): avoid. Assess ALT/AST and bilirubin levels prior to initiation, every 3 months during the first year of treatment, and annually thereafter. Interrupt dosing and monitor closely if ALT/AST elevations >5×ULN or ALT/AST >3×ULN with bilirubin >2×ULN; after resolution, consider resuming therapy. History of hepatobiliary disease or LFT elevations; consider more frequent monitoring. Perform baseline and follow-up eye exams. Moderate hepatic impairment: see Adult, Children. Severe hepatic impairment: do not use. Severe renal impairment or ESRD. Pregnancy. Nursing mothers.
Cystic fibrosis transmembrane conductance regulator (CFTR) corrector + CFTR potentiator.
Potentiated by strong (eg, ketoconazole, itraconazole, posaconazole, voriconazole, telithromycin, and clarithromycin) or moderate (eg, fluconazole, erythromycin) CYP3A inhibitors; adjust dose. Avoid food or drink containing grapefruit. Antagonized by strong CYP3A inducers (eg, rifampin, rifabutin, phenobarbital, carbamazepine, phenytoin, St. John’s wort); use not recommended. Caution with concomitant CYP2C9 substrates (eg, warfarin, glimepiride, glipizide), digoxin or other P-gp substrates with a narrow therapeutic index (eg, cyclosporine, everolimus, sirolimus, tacrolimus), OATP1B1 or OATP1B3 substrates (eg, statins, glyburide, nateglinide, repaglinide); monitor.
Headache, upper respiratory tract infection, abdominal pain, diarrhea, rash, ALT/AST increased, nasal congestion, blood CPK increased, rhinorrhea, rhinitis, influenza, sinusitis, blood bilirubin increased; non-congenital lens opacities/cataracts, hepatic injury.
Generic Drug Availability: