Select therapeutic use:
Indications for ORKAMBI:
Treatment of cystic fibrosis (CF) in patients ≥6yrs who are homozygous for the F508del mutation in the CFTR gene.
Limitations Of use:
Efficacy and safety not established in patients with CF other than those homozygous for the F508del mutation.
Take with fat-containing food (eg, eggs, avocados, nuts, butter, peanut butter, cheese pizza, whole-milk dairy products). 2 tabs (200mg/125mg) every 12hrs. Currently taking strong CYP3A inhibitors (eg, itraconazole, ketoconazole, posaconazole, voriconazole, telithromycin, clarithromycin): initially 1 tab (200mg/125mg) once daily for 1st week then continue with recommended daily dose. Hepatic impairment (moderate): 2 tabs in the AM and 1 tab in the PM; (severe): 1 tab in the AM and 1 tab in the PM, or less; use with caution.
<6yrs: not established. Take with fat-containing food (eg, eggs, avocados, nuts, butter, peanut butter, cheese pizza, whole-milk dairy products). 6–11yrs: 2 tabs (100mg/125mg) every 12hrs. Currently taking strong CYP3A inhibitors (eg, itraconazole, ketoconazole, posaconazole, voriconazole, telithromycin, clarithromycin): initially 1 tab (100mg/125mg) once daily for 1st week then continue with recommended daily dose. Hepatic impairment (moderate): 2 tabs in the AM and 1 tab in the PM; (severe): 1 tab in the AM and 1 tab in the PM, or less; use with caution.
If genotype is unknown, use an FDA cleared CF mutation test to detect the presence of the F508del mutation on both alleles of the CFTR gene. Advanced hepatic impairment. Assess ALT/AST and bilirubin levels prior to initiating therapy, every 3 months during the first year of treatment, and annually thereafter. If ALT/AST or bilirubin levels increased, monitor closely until resolved. Interrupt dosing if ALT/AST is >5XULN or if ALT/AST is >3XULN with bilirubin elevations >2XULN; after resolution, consider restarting. Monitor BP periodically and for respiratory events during treatment initiation in patients with ppFEV1 <40. Perform baseline and follow-up eye exams. Transplanted patients: not recommended. Severe renal impairment (CrCl ≤30mL/min) or ESRD. Pregnancy. Nursing mothers.
See Adults. Concomitant strong CYP3A inducers (eg, rifampin, rifabutin, phenobarbital, carbamazepine, phenytoin, St. John’s wort): not recommended. Concomitant sensitive CYP3A substrates or those with a narrow therapeutic index (eg, midazolam, triazolam, cyclosporine, everolimus, sirolimus, tacrolimus): not recommended. May affect CYP2B6, CYP2C8, CYP2C9, CYP2C19, P-gp substrates. Monitor digoxin. May antagonize montelukast, systemic corticosteroids (eg, prednisone, methylprednisolone), ibuprofen, citalopram, escitalopram, sertraline, omeprazole, esomeprazole, lansoprazole, ranitidine; dose adjustment may be needed. May antagonize clarithromycin, erythromycin, telithromycin; consider alternatives (eg, ciprofloxacin, azithromycin, levofloxacin). Concomitant itraconazole, ketoconazole, posaconazole, voriconazole: not recommended; if necessary, monitor closely or consider alternatives (eg, fluconazole). May antagonize repaglinide or affect sulfonylureas; dose adjustment may be needed. Concomitant warfarin; monitor INR. May reduce effectiveness of hormonal contraceptives and increase menstruation abnormality events; avoid.
Cystic fibrosis transmembrane conductance regulator (CFTR) potentiator.
Dyspnea, nasopharyngitis, nausea, diarrhea, upper respiratory tract infection, fatigue, abnormal respiration, increased blood creatinine phosphokinase, rash, flatulence, rhinorrhea, influenza.