Ivacaftor / Lumacaftor Dosage

Medically reviewed by Drugs.com. Last updated on Aug 22, 2023.

Applies to the following strengths: 94 mg-75 mg; 188 mg-150 mg; 125 mg-100 mg; 125 mg-200 mg

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.