Inborn errors of metabolism:

Indications for SYMDEKO:

Treatment of cystic fibrosis (CF) in patients ≥6yrs who are homozygous for the F508del mutation or have ≥1 mutation in the CFTR gene that is responsive to tezacaftor/ivacaftor.

Adults and Children:

<6yrs: not established. Swallow whole. Take with fat-containing food (eg, eggs, cheeses, nuts, whole milk, meats). 6–<12yrs (weighing <30kg): 1 tab (50mg/75mg) in the AM and 1 tab (75mg) in the PM, approx. 12hrs apart; 6–<12yrs (weighing ≥30kg) or ≥12yrs: 1 tab (100mg/150mg) in the AM and 1 tab (150mg) in the PM, approx. 12hrs apart. Concomitant moderate CYP3A inhibitors (6–<12yrs [weighing <30kg]): alternate 1 tab (50mg/75mg) in the AM or 1 tab (75mg) in the AM every other day; (6–<12yrs [weighing ≥30kg]) or ≥12yrs: alternate 1 tab (100mg/150mg) in the AM or 1 tab (150mg) in the AM every other day. Concomitant strong CYP3A inhibitors (6–<12yrs [weighing <30kg]): 1 tab (50mg/75mg) in the AM twice weekly, approx. 3–4 days apart; (6–<12yrs [weighing ≥30kg]) or ≥12yrs: 1 tab (100mg/150mg) in the AM twice weekly, approx. 3–4 days apart. Moderate hepatic impairment (6–<12yrs [weighing <30kg]): 1 tab (50mg/75mg) once daily, or less frequently if severe; (6–<12yrs [weighing ≥30kg]) or ≥12yrs: 1 tab (100mg/150mg) once daily, or less frequently if severe.

Warnings/Precautions:

If genotype is unknown, use an FDA-cleared CF mutation test to detect the presence of the CFTR mutation followed by bi-directional sequencing verification. Assess ALT/AST and bilirubin levels prior to initiating therapy, every 3 months during the first year of treatment, and annually thereafter. History of transaminase elevations; consider more frequent monitoring. Interrupt dosing and monitor closely if ALT/AST is >5×ULN or if ALT/AST is >3×ULN with bilirubin elevations >2×ULN; after resolution, consider restarting. Severe hepatic impairment. Perform baseline and follow-up eye exams. Severe renal impairment or ESRD. Pregnancy. Nursing mothers.

Pharmacologic Class:

Cystic fibrosis transmembrane conductance regulator (CFTR) corrector + CFTR potentiator.

Interactions:

Potentiated by strong (eg, ketoconazole, itraconazole, posaconazole, voriconazole, telithromycin, and clarithromycin) or moderate (eg, fluconazole, erythromycin) CYP3A inhibitors; adjust dose (see Adults and Children). Avoid food or drink containing grapefruit or Seville oranges. Concomitant strong CYP3A inducers (eg, rifampin, rifabutin, phenobarbital, carbamazepine, phenytoin, St. John’s wort): not recommended. Caution with concomitant digoxin or other P-gp substrates with a narrow therapeutic index (eg, cyclosporine, everolimus, sirolimus, tacrolimus): monitor.

Adverse Reactions:

Headache, nausea, sinus congestion, dizziness; transaminase elevations.

Generic Availability:

NO

How Supplied:

Tabs—56 (4x14)