Inborn errors of metabolism:
Indications for: ORKAMBI ORAL GRANULES
Treatment of cystic fibrosis (CF) in patients ≥2yrs 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: 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): max 1 tab in the AM and 1 tab in the PM, or less; use with caution.
<2yrs: not established. Take with fat-containing food (eg, eggs, avocados, nuts, butter, peanut butter, cheese pizza, whole-milk dairy products). Mix oral granules in 5mL soft food or liquid (eg, pureed fruits, yogurt, pudding, milk, juice). 2–5yrs (<14kg): 1 pkt (100mg/125mg) every 12hrs; (≥14kg): 1 pkt (150mg/188mg) every 12hrs. 6–11yrs: 2 tabs (100mg/125mg) every 12hrs. Currently taking strong CYP3A inhibitors: initially 1 tab once daily or 1 pkt every other day (2–5yrs) for 1st week then continue with recommended daily dose. Hepatic impairment: 2–5yrs (moderate): 1 pkt in the AM and 1 pkt every other day in the PM; (severe): max 1 pkt in the AM, or less; ≥6yrs (moderate): 2 tabs in the AM and 1 tab in the PM; (severe): max 1 tab in the AM and 1 tab in the PM, or less; all: use with caution.
ORKAMBI ORAL GRANULES Warnings/Precautions:
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 liver disease: monitor closely after initiation and reduce dose. 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.
ORKAMBI ORAL GRANULES Classification:
Cystic fibrosis transmembrane conductance regulator (CFTR) potentiator.
ORKAMBI ORAL GRANULES Interactions:
Ivacaftor potentiated by strong CYP3A inhibitors (eg, itraconazole, ketoconazole, posaconazole, voriconazole, telithromycin, clarithromycin); see Adults, Children. 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 antifungals (eg, 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.
Dyspnea, nasopharyngitis, nausea, diarrhea, upper respiratory tract infection, fatigue, abnormal respiration, increased blood creatinine phosphokinase, rash, flatulence, rhinorrhea, influenza; elevated transaminases, respiratory events.
Generic Drug Availability:
Tabs—112; Oral granules—56