lumacaftor/ivacaftor (Orkambi®)

SELF ADMINISTRATION - ORAL

Indications for Prior Authorization:

Cystic fibrosis

  • Treatment of cystic fibrosis (CF) in patients 12 years and older who are homozygous for the F508del mutation in the CFTR gene. If the patient's genotype is unknown, an FDA-cleared CF mutation test should be used to detect the presence of the F508del mutation on both alleles of the CFTR gene
  • Limitations of use: Efficacy and safety have not been established in patients with CF other than those homozygous for the F508del mutation

Patients must meet the following criteria for the indications above:

Cystic fibrosis

  • Patient is 12 years and older AND
  • Patient is homozygous for the F508del mutation in the CFTR gene OR
  • If the patient's genotype is unknown, an FDA-cleared CF mutation test should be used to detect the presence of the F508del mutation on both alleles of the CFTR gene

The Following Conditions Do Not Meet the Criteria for Use as Established by the WHA P & T Committee:

  • All non-FDA approved uses not listed in the approved indications

Dosing:

Maximum dose

  • Severe hepatic impairment (Child-Pugh class C): Lumacaftor 200 mg/ivacaftor 125 mg every 12 hours according to the prescribing information

Adult

  • Initial dosage: Lumacaftor 400 mg/ivacaftor 250 mg every 12 hours
  • Concomitant therapy:
    • Cytochrome P450 3A inhibitors: When initiating lumacaftor/ivacaftor in patients currently taking strong cytochrome P450 (CYP-450) 3A inhibitors (eg, itraconazole), reduce lumacaftor/ivacaftor dose to lumacaftor 200 mg/ivacaftor 125 mg once daily for the first week of treatment. Following this period, increase to lumacaftor 400 mg/ivacaftor 250 mg every 12 hours
    • If lumacaftor/ivacaftor is interrupted for more than 1 week while taking strong CYP3A inhibitors, re-titration must occur
    • No dosage adjustment is necessary when CYP3A inhibitors are initiated in patients already taking lumacaftor/ivacaftor

Pediatric 12 years and older

  • Initial dosage: Lumacaftor 400 mg/ivacaftor 250 mg every 12 hours
  • Concomitant therapy:
    • CYP3A inhibitors: When initiating lumacaftor/ivacaftor in patients currently taking strong CYP3A inhibitors (eg, itraconazole), reduce lumacaftor/ivacaftor dose to lumacaftor 200 mg/ivacaftor 125 mg once daily for the first week of treatment. Following this period, increase to lumacaftor 400 mg/ivacaftor 250 mg every 12 hours
    • If lumacaftor/ivacaftor is interrupted for more than 1 week while taking strong CYP3A inhibitors, re-titration must occur
    • No dosage adjustment is necessary when CYP3A inhibitors are initiated in patients already taking lumacaftor/ivacaftor

Younger than 12 years

  • Safety and efficacy have not been established

Renal function impairment

  • Creatinine clearance more than 30 mL/minute: No dosage adjustment necessary
  • Creatinine clearance 30 mL/minute or less: There are no dosage adjustments provided in the manufacturer's labeling; use with caution
  • End-stage renal disease: There are no dosage adjustments provided in the manufacturer's labeling; use with caution

Hepatic function impairment

  • Mild impairment (Child-Pugh class A): No dosage adjustment necessary
  • Moderate impairment (Child-Pugh class B): Reduce the dose to lumacaftor 400 mg /ivacaftor 250 mg in the morning and lumacaftor 200 mg/ivacaftor 125 mg in the evening
  • Severe impairment (Child-Pugh class C): Use with caution, weighing the risks and benefits of treatment. If therapy is appropriate, administer a maximum dose of lumacaftor 200 mg/ivacaftor 125 mg every 12 hours

Administration:  

  • Administer with fat-containing food (eg, eggs, avocados, nuts, butter, peanut butter, cheese pizza, whole-milk dairy products [eg, whole milk, cheese, yogurt])

Approval:

One year


 

Last review date: July 24, 2016