Usual Adult Dose for Cystic Fibrosis

Lumacaftor 400 mg/Ivacaftor 250 mg orally every 12 hours with fat-containing food

Comments:

• A fat containing meal or snack should be consumed just before or just after dosing. Examples include eggs, avocados, nuts, butter, peanut butter, cheese pizza, or whole-milk dairy products.
• 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; safety and efficacy in patients with cystic fibrosis other than homozygous F508del mutation has not been established.

Use: For the treatment of cystic fibrosis (CF) in patients who are homozygous for the F508del mutation in the CFTR gene.

Usual Pediatric Dose for Cystic Fibrosis

Age: 2 through 5 years; weight less than 14 kg: Lumacaftor 100 mg/Ivacaftor 125 mg orally every 12 hours with fat-containing food
Age: 2 through 5 years: weight 14 kg or greater: Lumacaftor 150 mg/Ivacaftor 188 mg orally every 12 hours with fat-containing food

Age: 6 through 11 years: Lumacaftor 200 mg/Ivacaftor 250 mg orally every 12 hours with fat-containing food

Age: 12 years or older: Lumacaftor 400 mg/Ivacaftor 250 mg orally every 12 hours with fat-containing food

Comments:

• Pediatric patients 2 through 5 years of age should receive oral granules; pediatric patients over 6 years of age, should be dosed with tablets.
• A fat containing meal or snack should be consumed just before or just after dosing. Examples include eggs, avocados, nuts, butter, peanut butter, cheese pizza, or whole-milk dairy products.
• 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; safety and efficacy in patients with cystic fibrosis other than homozygous F508del mutation has not been established.

Use: For the treatment of cystic fibrosis (CF) in patients 2 years or older who are homozygous for the F508del mutation in the CFTR gene.

Renal Dose Adjustments

• Mild to moderate renal disease: No adjustment recommended
• Severe renal impairment (CrCl less than or equal to 30 mL/min) or end-stage renal disease: Caution is recommended

Liver Dose Adjustments

Mild liver dysfunction (Child-Pugh Class A): No adjustment recommended

Moderate liver dysfunction (Child-Pugh Class B):

• Age: 2 through 5 years; weight less than 14 kg: Reduce dose to lumacaftor 100 mg/ivacaftor 125 mg orally once a day in the morning and lumacaftor 100 mg/ivacaftor 125 mg orally every other day in the evening
• Age: 2 through 5 years: weight 14 kg or greater: Reduce dose to lumacaftor 150 mg/ivacaftor 188 mg orally once a day in the morning and lumacaftor 150 mg/ivacaftor 188 mg orally every other day in the evening
• Age: 6 through 11 years: Reduce dose to lumacaftor 200 mg/ivacaftor 250 mg orally in the morning and lumacaftor 100 mg/ivacaftor 125 mg in the evening (12 hours later)
• Age: 12 years or older: Reduce dose to lumacaftor 400 mg/Ivacaftor 250 mg orally in the morning and lumacaftor 200 mg/ivacaftor 125 mg in the evening (12 hours later)

Severe liver dysfunction (Child-Pugh Class C): First weigh the risk and benefits of use, if used:

• Age: 2 through 5 years; weight less than 14 kg: Reduce dose to lumacaftor 100 mg/ivacaftor 125 mg orally once a day in the morning or less frequently
• Age: 2 through 5 years: weight 14 kg or greater: Reduce dose to lumacaftor 150 mg/ivacaftor 188 mg orally once a day in the morning or less frequently
• Age: 6 through 11 years: Reduce dose to lumacaftor 100 mg/ivacaftor 125 mg orally every 12 hours or less frequently
• Age: 12 years or older: Reduce dose to lumacaftor 200 mg/Ivacaftor 125 mg orally every 12 hours or less frequently

For patients developing AST or ALT elevations greater than 5 times the upper limit of normal (5 x ULN) or AST or ALT elevations 3 x ULN with bilirubin elevated to 2 x ULN: Interrupt dosing; once levels have normalized, consider the risk and benefits of therapy before resuming therapy

Dose Adjustments

Elderly: As cystic fibrosis is largely a disease of children and adults, clinical trials did not include sufficient numbers of patients over 65 years to determine whether they responded differently.

Concomitant Use of CYP450 3A Inhibitors: Initiating CYP450 3A4 Inhibitors while already on lumacaftor/ivacaftor: No dose adjustment is necessary
Initiating lumacaftor/ivacaftor while taking strong CYP450 3A inhibitors OR Interrupting therapy for more than 1 week while concomitantly taking a strong CYP450 3A inhibitor (e.g., itraconazole):

• Age: 2 through 5 years; weight less than 14 kg: Reduce dose to lumacaftor 100 mg/ivacaftor 125 mg orally every other day for 1 week, then resume recommended daily dose
• Age: 2 through 5 years: weight 14 kg or greater: Reduce dose to lumacaftor 150 mg/ivacaftor 188 mg orally every other day for 1 week, then resume recommended daily dose
• Age: 6 through 11 years: Reduce dose lumacaftor 100 mg/ivacaftor 125 mg orally once a day for first week, then resume recommended daily dose.
• Age: 12 years or older: Reduce dose to lumacaftor 200 mg/ivacaftor 125 mg orally once a day for first week, then resume recommended daily dose.

Concomitant Use with Strong CYP450 3A Inducers: Not recommended

Patients who have Undergone Organ Transplantation: Use is not recommended due to potential drug-drug interactions

Precautions

CONTRAINDICATIONS: None

Safety and efficacy have not been established in patients younger than 2 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:
Take orally every 12 hours with fat-containing food (e.g., butter, eggs, cheeses, nuts, peanut butter, whole-milk dairy products, avocados)

• Tablets: Swallow whole; do not break, crush, chew, or dissolve
• Granules: Mix 1 packet with 5 mL of soft food or liquid; consume entire mixture promptly

Missed dose: If a dose is missed within 6 hours of the usual scheduled time, take the dose immediately with a fat-containing meal; if more than 6 hours have elapsed, skip that dose and resume the normal schedule for the following dose; a double dose should not be taken to make up for a missed dose

Stability:

• Oral granules: once mixed with soft food or liquid (examples: pureed fruit, yogurt, pudding, milk, or juice): Stable for 1 hour
• Food should be at room temperature or below prior to mixing with granules

General:

• The efficacy for use of this product in patients 2 through 11 years is extrapolated from efficacy in patients 12 years or older homozygous for the F508del mutation in the CFTR gene; additionally, pharmacokinetic analyses and safety profiles are similar.

Monitoring:

• Cardiovascular: Monitor blood pressure periodically throughout treatment
• Hepatic: Measure ALT, AST, and bilirubin prior to initiation, every 3 months for first year, then annually; consider more frequent monitoring in patients with a history of ALT, AST, or bilirubin elevations
• Ophthalmologic: Baseline and follow-up ophthalmological exams are recommended in pediatric patients
• Respiratory Additional monitoring during initiation is recommended in patients with percent predicted FEV1 less than 40

Patient advice:

• Read the Patient Information
• Patients should be informed that worsening liver function has been reported and if signs or symptoms of hepatotoxicity develop, they should contact a health professional right away (e.g., loss of appetite, dark urine, nausea or vomiting, yellowing skin or eyes)
• Patients should be instructed to not to start or stop any medications without discussing this with their healthcare provider as drug interactions are a concern with this drug.
• Patients should understand that hormonal contraceptives should not be relied upon as an effective method of birth control when used with this drug.

Frequently asked questions

• How do you take Orkambi?
• What is the difference between Symdeko and Orkambi?