Usual Adult Dose for Cystic Fibrosis

Morning dose: 2 (elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg) tablets orally each morning
Evening dose: 1 (ivacaftor 150 mg) tablet orally each evening

Comments:

• Doses should be taken approximately 12 hours apart; swallow tablets whole; tablets should be taken with fat-containing food.
• If genotype is unknown, an FDA-cleared cystic fibrosis (CF) mutation test should be used to confirm the presence of at least one F508del mutation or a mutation that is responsive based on in vitro data.

Use: For the treatment of CF in patients who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene or a mutation in the CFTR gene that is responsive based on in vitro data.

Usual Pediatric Dose for Cystic Fibrosis

Age: 6 to 12 years; weight: Less than 30 kg:

• Morning dose: 2 (elexacaftor 50 mg/tezacaftor 25 mg/ivacaftor 37.5 mg) tablets orally each morning
• Evening dose: 1 (ivacaftor 75 mg) tablet orally each evening

Age: 6 to 12 years; weight: 30 kg or more:

• Morning dose: 2 (elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg) tablets orally each morning
• Evening dose: 1 (ivacaftor 150 mg) tablet orally each evening

Age: 12 years or older:
Morning dose: 2 (elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg) tablets orally each morning
Evening dose: 1 (ivacaftor 150 mg) tablet orally each evening

Comments:

• Doses should be taken approximately 12 hours apart; swallow tablets whole; tablets should be taken with fat-containing food.
• If genotype is unknown, an FDA-cleared cystic fibrosis (CF) mutation test should be used to confirm the presence of at least one F508del mutation or a mutation that is responsive based on in vitro data.

Use: For the treatment of CF in patients aged 6 years or older who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene or a mutation in the CFTR gene that is responsive based on in vitro data.

Renal Dose Adjustments

Mild to moderate renal impairment (CrCl 30 mL/min/1.73 m2 or greater): No adjustment recommended
Severe renal impairment (CrCl less than 30 mL/min/1.73 m2) 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): Not recommended unless clear medical need and benefit exceeds risks; if used, reduce dose and increase liver function test monitoring

• Dose reduction for moderate hepatic impairment:
• Day 1: Two elexacaftor/tezacaftor/ivacaftor tablets in the morning; no evening dose of ivacaftor
• Day 2: One elexacaftor/tezacaftor/ivacaftor tablet in the morning; no evening dose of ivacaftor
• Continue alternating Day 1 and Day 2; no evening doses of ivacaftor are to be taken

SEVERE hepatic impairment (Child-Pugh Class C): Not recommended

DURING THERAPY:

• If significant transaminase elevations occur (e.g., ALT or AST elevations to greater than 5 times the upper limit of normal [5 x ULN], or ALT or AST elevations to greater than 3 x ULN with bilirubin elevations greater than 2 x ULN): Interrupt dosing and follow laboratory tests closely until abnormalities resolve
• Once transaminase elevations resolve, the benefits and risks of resuming treatment should be considered

Dose Adjustments

Concomitant use of Moderate CYP450 3A Inhibitors:

• Omit evening ivacaftor dose and alternate morning dose as follows: Two fixed dose tablets (elexacaftor/tezacaftor/ivacaftor) orally every other morning alternating with one ivacaftor tablet on alternate mornings

Concomitant use of Strong CYP450 3A Inhibitors:

• Omit evening dose and take two fixed dose tablets (elexacaftor/tezacaftor/ivacaftor) orally twice a week, approximately 3 to 4 days apart (i.e., 2 fixed dose tablets on day 1 and day 4; no doses on day 2 and day 3)

Avoid food or drink containing grapefruit during therapy

Concomitant Administration with Strong CYP450 3A Inducers: Not Recommended

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 twice a day approximately 12 hours apart
• Swallow tablet(s) whole
• Take tablets with fat-containing food such as butter, peanut butter, cheeses, nuts, whole milk, or meats
• Co-packaged regimen consists fixed dose combination tablet (elexacaftor/tezacaftor/ivacaftor) and a single ingredient tablet (ivacaftor):
• Elexacaftor 50 mg/tezacaftor 25 mg/ivacaftor 37.5 mg tablets are light orange debossed with T50 on one side and plain on the other side
• Ivacaftor 75 mg tablets are light blue with V75 debossed on one side and plain on the other side
• Elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg tablets are orange debossed with T100 on one side and plain on the other side
• Ivacaftor 150 mg tablets are light blue with V150 on one side and plain on the other side

Missed dose:

• If 6 hours or LESS has passed since missed morning or evening dose: Take as soon as remembered with fat containing food and continue on normal schedule
• If MORE than 6 hours has passed since missing the morning dose: Take the morning dose as soon as possible and skip the evening dose; resume normal dosing the following morning
• If MORE than 6 hours has passed since missing evening dose: Skip the evening dose; resume normal dosing the following morning
• Patients should be instructed not to double up and take morning and evening doses at the same time; patients should be instructed to contact their healthcare provided if they have additional questions

General:

• Supplied as co-packaged blister pack; elexacaftor/tezacaftor/ivacaftor are orange tablets and the ivacaftor tablets are light blue.
• This combination drug is for treatment of patients with cystic fibrosis (CF) who have at least one F508del mutation in the CF transmembrane conductance regulator (CFTR) gene; this gene mutation is estimated to represent 90% of the CF population.
• The presence of at least one F508del mutation should be confirmed with an FDA-cleared genotyping assay prior to initiating therapy.

Monitoring:

• Perform liver function tests (ALT, AST, and bilirubin) prior to therapy, every 3 months during the first year, and annually thereafter; more frequent testing should be considered in patients with a history of hepatobiliary disease or liver function test elevations
• Pediatric patients should undergo baseline and follow-up ophthalmological examinations

Patient advice:

• Patients should be instructed to read the US FDA-approved patient labeling (Patient Information).
• Patients should understand that there are a number of drug interactions that may reduce the efficacy of therapy; they should report all medications, herbal supplements, and vitamins they are starting/stopping to their healthcare provider; they should avoid food or drink containing grapefruit during therapy.
• Patients should be instructed to take tablets with fat containing foods approximately 12 hours apart; they should understand what do in case of a missed dose.
• Patients should be instructed to speak with their healthcare provider if they are pregnant or planning to become pregnant or breastfeeding.

Frequently asked questions

• What is Trikafta?