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:

Administer each dose with a fat-containing meal or snack consumed just before or after dosing.
If the patient's genotype is unknown, an FDA-cleared cystic fibrosis (CF) mutation test should be used to detect the presence of the F508del mutation on both alleles of the CFTR gene.
The safety and efficacy of this drug in patients with cystic fibrosis other than homozygous F508del mutation has not been established.

Use: For the treatment of CF in patients who are homozygous for the F508del mutation in the CFTR gene

Usual Pediatric Dose for Cystic Fibrosis

AGE 1 TO 2 YEARS:

Weight 7 kg to less than 9 kg: Lumacaftor 75 mg-ivacaftor 94 mg orally every 12 hours
Weight 9 kg to less than 14 kg: Lumacaftor 100 mg-ivacaftor 125 mg orally every 12 hours
Weight 14 kg or greater: Lumacaftor 150 mg-ivacaftor 188 mg orally every 12 hours

AGE 2 THROUGH 5 YEARS:

Weight less than 14 kg: Lumacaftor 100 mg-ivacaftor 125 mg orally every 12 hours
Weight 14 kg or greater: Lumacaftor 150 mg-ivacaftor 188 mg orally every 12 hours

AGE 6 THROUGH 11 YEARS: Lumacaftor 200 mg-ivacaftor 250 mg orally every 12 hours

AGE 12 YEARS OR OLDER: Lumacaftor 400 mg-ivacaftor 250 mg orally every 12 hours

Comments:

Administer each dose with a fat-containing meal or snack consumed just before or after dosing.
Pediatric patients 1 through 5 years of age should receive oral granules.
Pediatric patients over 6 years of age should be dosed with oral tablets.
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 safety and efficacy of this drug in patients with cystic fibrosis other than homozygous F508del mutation has not been established.

Use: For the treatment of CF in patients 1 year or older who are homozygous for the F508del mutation in the CFTR gene

Renal Dose Adjustments

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

Comments:

This drug has not been studied in patients with any degree of renal impairment.

Liver Dose Adjustments

MILD LIVER DYSFUNCTION (Child-Pugh A): No adjustment recommended

MODERATE LIVER DYSFUNCTION (Child-Pugh B):
Age 1 to 2 Years:

Weight 7 kg to less than 9 kg: Reduce dose to lumacaftor 75 mg-ivacaftor 94 mg orally every morning and every other day in the evening
Weight 9 kg to less than 14 kg: Reduce dose to lumacaftor 100 mg-ivacaftor 125 mg orally every morning and every other day in the evening
Weight 14 kg or greater: Reduce dose to lumacaftor 150 mg-ivacaftor 188 mg orally every morning and every other day in the evening

Age 2 through 5 Years:

Weight less than 14 kg: Reduce dose to lumacaftor 100 mg-ivacaftor 125 mg orally every morning and every other day in the evening
Weight 14 kg or greater: Reduce dose to lumacaftor 150 mg-ivacaftor 188 mg orally every morning and 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 orally 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 orally in the evening (12 hours later)

SEVERE LIVER DYSFUNCTION (Child-Pugh C): Consider the risk and benefits prior to use.
Age 1 to 2 Years:

Weight 7 kg to less than 9 kg: Reduce dose to lumacaftor 75 mg-ivacaftor 94 mg orally once a day in the morning or less frequently
Weight 9 kg to less than 14 kg: Reduce dose to lumacaftor 100 mg-ivacaftor 125 mg orally once a day in the morning or less frequently
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 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
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

TRANSAMINASE ELEVATIONS:

For patients developing AST/ALT elevations greater than 5 times the upper limit of normal (5 x ULN) without elevated bilirubin, OR for AST/ALT elevations greater than 3 x ULN with bilirubin greater than 2 x ULN: Interrupt dosing; once levels have normalized, consider the risk and benefits of therapy before resuming therapy

Dose Adjustments

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 when interrupting therapy for more than 1 week while concomitantly taking a strong CYP450 3A inhibitor:
Age 1 to 2 Years:

Weight 7 kg to less than 9 kg: Lumacaftor 75 mg-ivacaftor 94 mg orally every other day for 1 week, then resume recommended daily dose
Weight 9 kg to less than 14 kg: Lumacaftor 100 mg-ivacaftor 125 mg orally every other day for 1 week, then resume recommended daily dose
Weight 14 kg or greater: Lumacaftor 150 mg-ivacaftor 188 mg orally every other day for 1 week, then resume recommended daily dose

Age 2 through 5 Years:

Weight less than 14 kg: Lumacaftor 100 mg-ivacaftor 125 mg orally every other day for 1 week, then resume recommended daily dose
Weight 14 kg or greater: Lumacaftor 150 mg-ivacaftor 188 mg orally every other day for 1 week, then resume recommended daily dose

Age 6 through 11 Years: Lumacaftor 100 mg-ivacaftor 125 mg orally once a day for 1 week, then resume recommended daily dose

Age 12 Years or Older: Lumacaftor 200 mg-ivacaftor 125 mg orally once a day for 1 week, then resume recommended daily dose

CONCOMITANT USE WITH STRONG CYP450 3A INDUCERS: Not recommended

Precautions

CONTRAINDICATIONS: None

Safety and efficacy have not been established in patients younger than 1 year old.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

For oral use
Administer each dose in the morning and evening, every 12 hours.
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.
Oral granules: Mix 1 packet with 5 mL of soft food or liquid at room temperature; consume promptly.
Missed dose: If a dose is missed within 6 hours of 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.

Storage and stability:

Store at 20C to 25C (68F to 77F); excursions permitted to 15C to 30C (59F to 86F).
Oral granules: Stable for 1 hour once mixed with soft food or liquid, such as pureed fruit, yogurt, pudding, milk, juice, or formula.

General:

Safety and efficacy have not been established in patients with CF other than those homozygous for the F508del mutation.
There is no safety and efficacy data on the use of this drug in older adults. As cystic fibrosis is largely a disease of children and adults, clinical trials did not include sufficient patients over 65 years.
Use is not recommended in patients who have undergone organ transplantation due to potential drug-drug interactions.

Monitoring:

Cardiovascular: Blood pressure (periodically during therapy)
Hepatic: 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 US FDA-approved patient labeling (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.