Usual Adult Dose for Cystic Fibrosis

1 tablet (tezacaftor 100 mg/ivacaftor 150 mg) orally in the morning and 1 tablet (ivacaftor 150 mg) orally in the evening

Comments:

• Dosing should be approximately 12 hours apart; tablets should be swallowed whole with fat-containing foods such as those prepared with butter or oils, those containing eggs, cheeses, nuts, whole milk, or meats.
• When the genotype is not known, an FDA-cleared cystic fibrosis (CF) mutation test should be used to detect the presence of a CF transmembrane conductance regulator (CFTR) mutation followed by verification with bi-directional sequencing when recommended by the mutation test instructions for use.

Use: For the treatment of patients with cystic fibrosis who are homozygous for the F508del mutation or who have at least 1 mutation in the CFTR gene that is responsive to this combination drug based on in vitro data and/or clinical evidence.

Usual Pediatric Dose for Cystic Fibrosis

6 to less than 12 years; weight less than 30 kg:

• Take 1 tablet (tezacaftor 50 mg/ivacaftor 75 mg) orally in the morning and 1 tablet (ivacaftor 75 mg) orally in the evening

6 to less than 12 years; weight 30 kg or more:

• Take 1 tablet (tezacaftor 100 mg/ivacaftor 150 mg) orally in the morning and 1 tablet (ivacaftor 150 mg) orally in the evening

12 years or older:
Take 1 tablet (tezacaftor 100 mg/ivacaftor 150 mg) orally in the morning and 1 tablet (ivacaftor 150 mg) orally in the evening

Comments:

• Dosing should be approximately 12 hours apart; tablets should be swallowed whole with fat-containing foods such as those prepared with butter or oils, those containing eggs, cheeses, nuts, whole milk, or meats.
• When the genotype is not known, an FDA-cleared cystic fibrosis (CF) mutation test should be used to detect the presence of a CF transmembrane conductance regulator (CFTR) mutation followed by verification with bi-directional sequencing when recommended by the mutation test instructions for use.

Use: For the treatment of patients with cystic fibrosis who are homozygous for the F508del mutation or who have at least 1 mutation in the CFTR gene that is responsive to this combination drug based on in vitro data and/or clinical evidence.

Renal Dose Adjustments

Mild to moderate renal impairment: No adjustment recommended
Severe renal impairment or ESRD: Use with caution

Liver Dose Adjustments

MILD hepatic impairment (Child-Pugh Class A): No adjustment recommended
MODERATE hepatic impairment (Child-Pugh Class B):

• Age: 6 to less than 12 years weighing less than 30 kg: 1 tablet (tezacaftor 50 mg/ivacaftor 75 mg) orally once a day in the morning; no evening dose
• Age: 6 to less than 12 years weighing 30 kg or greater: 1 tablet (tezacaftor 100 mg/ivacaftor 150 mg) orally once a day in the morning; no evening dose
• Age: 12 years or older: 1 tablet (tezacaftor 100 mg/ivacaftor 150 mg) orally once a day in the morning; no evening dose

SEVERE hepatic impairment (Child-Pugh C):

• Age: 6 to less than 12 years weighing less than 30 kg: 1 tablet (tezacaftor 50 mg/ivacaftor 75 mg) orally once a day in the morning or less frequently; no evening dose
• Age: 6 to less than 12 years weighing 30 kg or greater: 1 tablet (tezacaftor 100 mg/ivacaftor 150 mg) orally once a day in the morning or less frequently; no evening dose
• Age: 12 years or older: 1 tablet (tezacaftor 100 mg/ivacaftor 150 mg) orally once a day in the morning or less frequently; no evening dose

If transaminase elevations occur during therapy (i.e, ALT or AST greater than 5 x upper limit of normal (ULN), or ALT or AST greater than 3 x ULN with bilirubin greater than 2 x ULN, dosing should be interrupted and laboratory tests closely followed until abnormalities resolve; following resolution of transaminase elevations consider the benefits and risks of resuming treatment

Dose Adjustments

Concomitant use with Strong CYP450 3A Inhibitors:

• Age: 12 years or older: 1 tablet (tezacaftor 100 mg/ivacaftor 150 mg) orally twice a week, approximately every 3 to 4 days; no evening doses
• Age: 6 to less than 12 years weighing 30 kg or greater: 1 tablet (tezacaftor 100 mg/ivacaftor 150 mg) orally twice a week, approximately every 3 to 4 days; no evening doses
• Age: 6 to less than 12 years weighing less than 30 kg: 1 tablet (tezacaftor 50 mg/ivacaftor 75 mg) orally twice a week, approximately every 3 to 4 days; no evening doses

Concomitant use with Moderate CYP450 3A Inhibitors:

• Age: 12 years or older: 1 tablet (tezacaftor 100 mg/ivacaftor 150 mg) orally every other morning alternating with one tablet (ivacaftor 150 mg) orally every other morning on alternate days; no evening dose
• Age: 6 to less than 12 years weighing 30 kg or greater: 1 tablet (tezacaftor 100 mg/ivacaftor 150 mg) orally every other morning alternating with one tablet (ivacaftor 150 mg) orally every other morning on alternate days; no evening dose
• Age: 6 to less than 12 years weighing less than 30 kg: 1 tablet (tezacaftor 50 mg/ivacaftor 75 mg) orally every other morning alternating with one tablet (ivacaftor 75 mg) orally every other morning on alternate days; no evening dose

Co-administration with Strong CYP450 3A inducers is not recommended
AVOID food or drink containing grapefruit or Seville oranges during treatment

Precautions

CONTRAINDICATIONS: None

Safety and efficacy have not been established in patients younger than 6 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Take orally in the morning and in the evening (approximately 12 hours apart) with food that contains fat
• Tablets should be swallowed whole
• A typical cystic fibrosis diet will satisfy the fat requirement; examples of foods that contains fat include: eggs, butter, peanut butter, cheese pizza, and whole-milk dairy products such as whole milk, cheese, and yogurt
• Therapy requires 2 different tablets, the morning dose is a combination tablet consisting of tezacaftor and ivacaftor, the evening dose is ivacaftor alone; dose modifications may be needed which may result in omitting the evening dose and taking morning dose less frequently

Missed dose:

• If 6 hours or less has passed since dose has been missed: Take dose as soon as possible with fat-containing food
• If more than 6 hours has passed since dose has been missed: Skip the missed dose and resume usual dosing schedule

General:

• Comparable results were obtained among patients with severe lung dysfunction and those without.
• This drug should be administered with food that contains fat to ensure optimal absorption; a typical cystic fibrosis diet should satisfy this requirement.

Monitoring:

• Obtain transaminase levels (ALT and AST) prior to initiating therapy, every 3 months for the first year, and annually thereafter; more frequent monitoring should be considered in patients with a history of transaminase elevations.
• Ophthalmological exam should be performed at baseline and periodically in pediatric patients.

Patient advice:

• Patients should be instructed to read the US FDA-approved patient labeling (Patient Information).
• Patients should understand that this therapy requires them to take 2 different tablets, the morning dose is a combination of tezacaftor and ivacaftor, while the evening dose is ivacaftor only; tablets should be taken orally approximately 12 hours apart with a food that contains fat; dose adjustments may be needed which could result in omitting the evening dose and taking the morning dose less frequently.
• Patients should be advised that there are major drug interactions that affect how well this drug may work; patients should be instructed to speak with their healthcare provider regarding all medications they are taking or plan to take including over the counter medicines, vitamins, and herbal supplements.
• Patients should be instructed to avoid food or drink that contain grapefruit or Seville oranges.
• Patients should be instructed to avoid driving or operating hazardous machinery until it is known how this drug affects them; this drug may cause dizziness.

Frequently asked questions

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