Ivacaftor / Lumacaftor Dosage

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

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.

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Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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