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DOSING & ADMINISTRATION1,2

    2 to <6 Years

    2 to <6 Years

    On this Page:
    Dosing Information Administration Dosing Adjustments Missed Dose
    On this Page:
    Dosing Information Administration Dosing Adjustments Missed Dose

    DOSING INFORMATION

    Recommended dosing for patients aged 2 to <6 years1

    • Laboratory testing for liver function is recommended prior to TRIKAFTA® (elexacaftor/tezacaftor/ivacaftor and ivacaftor) initiation and treatment. Please see Dosage and Administration section of the full Prescribing Information
    • TRIKAFTA should be taken with fat-containing meals or snacks. Examples include food prepared with butter or oils or those containing eggs, cheeses, nuts, whole milk, meats, or peanut butter
    • Laboratory testing for liver function is recommended prior to TRIKAFTA® (elexacaftor/tezacaftor/ivacaftor and ivacaftor) initiation and treatment. Please see Dosage and Administration section of the full Prescribing Information
    • TRIKAFTA  
      should be taken with fat-containing meals or snacks. Examples include food prepared with butter or oils or those containing eggs, cheeses, nuts, whole milk, meats, or peanut butter
    • Morning and evening doses should be taken approximately 12 hours apart
    • Food or drink containing grapefruit should be avoided during treatment with TRIKAFTA

    For patients aged 2 to <6 years weighing <14 kg (<31 lb)1,2

    TRIKAFTA in cartons for patients aged 6 through 11 years weighing ≥30 kg (≥66 lb) and 12 years and older

    For patients aged 2 to <6 years weighing ≥14 kg (≥ 31 lb)1,2

    TRIKAFTA in cartons for patients aged 6 through 11 years weighing ≥30 kg (≥66 lb) and 12 years and older
    WeightMorning DoseEvening Dose 
    <14 kg (<31 lb)1,21 white and blue packet of:
    elexacaftor 80 mg/
    tezacaftor 40 mg/
    ivacaftor 60 mg    		1 white and green packet of:
    ivacaftor 59.5 mg
    ≥14 kg (≥31 lb)1,21 white and orange packet of:
    elexacaftor 100 mg/
    tezacaftor 50 mg/
    ivacaftor 75 mg    		1 white and pink packet of:
    ivacaftor 75 mg
    Weight
    <14 kg (<31 lb)1,2
    Morning Dose
    1 white and blue packet of:
    elexacaftor 80 mg/
    tezacaftor 40 mg/
    ivacaftor 60 mg
    Evening Dose 
    1 white and green packet of:
    ivacaftor 59.5 mg
    Weight
    ≥14 kg (≥31 lb)1,2
    Morning Dose
    1 white and orange packet of:
    elexacaftor 100 mg/
    tezacaftor 50 mg/
    ivacaftor 75 mg
    Evening Dose 
    1 white and pink packet of:
    ivacaftor 75 mg
    • Elexacaftor, tezacaftor, and ivacaftor oral granules are white to off-white, sweetened, unflavored granules approximately 2 mm in diameter
    • Ivacaftor oral granules are white to off-white, sweetened, unflavored granules approximately 2 mm in diameter

    ADMINISTRATION

    How to administer oral granule doses of TRIKAFTA1

    Step 1

    Preparation

    • Caregiver should hold the packet with the perforation on top, shake the packet gently to settle the granules, and tear or cut the packet open along the perforations
    • Caregiver should mix all the granules into 1 teaspoon (5 mL) of age-appropriate soft food or liquid
    • Food or liquid should be at or below room temperature

    Examples of soft foods or liquids include:

    Puréed fruits or vegetablesYogurt or applesauceMilk, juice or water

    Note: Use thickened food/purée in younger patients who are adjusting to solid foods.

    Step 2

    Administration

    • After mixing granules, caregiver should give the dose within 1 hour
    • Caregiver should make sure the child finishes the dose completely

    Step 3

    Give fat-containing food

    • Food that contains fat must be taken just before or after the oral granules dose. Examples of fat-containing foods include:

    • Eggs
    • Avocado
    • Nuts
    • Butter

     

    • Peanut butter
    • Cheese pizza
    • Whole-milk dairy products (eg. whole milk, cheese, and yogurt)

    Note: The list above includes only examples. Parents/caretakers can try other fat- containing foods that work best for the patient. Food or drink containing grapefruit should be avoided during treatment with TRIKAFTA.

    Step 1

    Preparation

    • Caregiver should hold the packet with the perforation on top, shake the packet gently to settle the granules, and tear or cut the packet open along the perforations
    • Caregiver should mix all the granules into 1 teaspoon (5 mL) of age-appropriate soft food or liquid
    • Food or liquid should be at or below room temperature

    Examples of soft foods or liquids include:

    Puréed fruits or vegetables

    Yogurt or applesauce

    Milk, juice or water

    Note: Use thickened food/purée in younger patients who are adjusting to solid foods.

    Step 2

    Administration

    • After mixing granules, caregiver should give the dose within 1 hour
    • Caregiver should make sure the child finishes the dose completely

    Step 3

    Give fat-containing food

    • Food that contains fat must be taken just before or after the oral granules dose. Examples of fat-containing foods include:

    • Eggs
    • Avocado
    • Nuts
    • Butter
    • Peanut butter
    • Cheese pizza
    • Whole-milk dairy products (eg. whole milk, cheese, and yogurt)

    Note: The list above includes only examples. Parents/caretakers can try other fat- containing foods that work best for the patient. Food or drink containing grapefruit should be avoided during treatment with TRIKAFTA.

    It is important for patients to consume the entire dose of granules within 1 hour after mixing

    DOSING ADJUSTMENTS

    Dose adjustments for hepatic impairment in patients aged 2 to <6 years1

    In patients with mild hepatic impairment (Child-Pugh Class A)

    NO DOSE ADJUSTMENT

    • Liver function tests should be closely monitored1
    In patients with moderate hepatic impairment (Child-Pugh Class B)

    TREATMENT IS NOT RECOMMENDED

    USE SHOULD ONLY BE CONSIDERED WHEN THERE IS A CLEAR MEDICAL NEED AND THE BENEFITS ARE EXPECTED TO OUTWEIGH THE RISKS

    If used, TRIKAFTA should be used with caution at a reduced dose, as follows:

    • Days 1-3: one packet of elexacaftor/tezacaftor/ ivacaftor granules each day
    • Day 4: no dose
    • Day 5-6: one packet of elexacaftor/tezacaftor/ ivacaftor granules each day
    • Day 7: no dose

    Repeat above dosing schedule each week.

    The evening dose of the ivacaftor granules should not be taken.

    • Liver function tests should be closely monitored1
    In patients with severe hepatic impairment (Child-Pugh Class C)

    SHOULD NOT BE USED

    • TRIKAFTA has not been studied in patients with severe hepatic impairment, but the exposure is expected to be higher than in patients with moderate hepatic impairment1
    In patients with mild hepatic impairment (Child-Pugh Class A)

    NO DOSE ADJUSTMENT

    • Liver function tests should be closely monitored1
    In patients with moderate hepatic impairment (Child-Pugh Class B)

    TREATMENT IS NOT RECOMMENDED

    USE SHOULD ONLY BE CONSIDERED WHEN THERE IS A CLEAR MEDICAL NEED AND THE BENEFITS ARE EXPECTED TO OUTWEIGH THE RISKS

    If used, TRIKAFTA should be used with caution at a reduced dose, as follows:

    • Days 1-3: one packet of 
      elexacaftor/tezacaftor/ivacaftor granules each day
    • Day 4: no dose
    • Day 5-6: one packet of 
      elexacaftor/tezacaftor/ivacaftor granules each day
    • Day 7: no dose

    Repeat above dosing schedule each week.

    The evening dose of the ivacaftor granules should not be taken.

    • Liver function tests should be closely monitored1
    In patients with severe hepatic impairment (Child-Pugh Class C)

    SHOULD NOT BE USED

    • TRIKAFTA has not been studied in patients with severe hepatic impairment, but the exposure is expected to be higher than in patients with moderate hepatic impairment1

    Dose adjustments for renal impairment in patients aged 2 to <6 years

    • No dose adjustment is recommended in patients with mild (eGFR 60 to <90 mL/min/1.73 m2) or moderate (eGFR 30 to <60 mL/min/1.73 m2) renal impairment. TRIKAFTA has not been studied in patients with severe (eGFR <30 mL/min/1.73 m2) renal impairment or end-stage renal disease and should be used with caution in these patients1

    Drug interaction profiles and related dosing considerations for patients aged 2 to <6 years

    WeightDrug Interaction ProfileDosing Considerations
    <14 kg (<31 lb)1,2Strong CYP3A inducers including1: rifampin, rifabutin, phenobarbital, carbamazepine, phenytoin, St. John's wort (Hypericum perforatum)CONCOMITANT USE
    NOT RECOMMENDED
    Strong CYP3A inhibitors including1: ketoconazole, itraconazole, posaconazole, voriconazole, telithromycin, clarithromycin

    IN THE MORNING (TWICE A WEEK)

    • DAY 1: elexacaftor 80 mg/
      tezacaftor 40 mg/
      ivacaftor 60 mg
      (1 white and blue packet)
    • DAY 4a: elexacaftor 80 mg/
      tezacaftor 40 mg/
      ivacaftor 60 mg
      (1 white and blue packet)

    NO PACKET IN THE EVENING

    Moderate CYP3A inhibitors including1: fluconazole, erythromycin

    ALTERNATE GRANULES EVERY MORNING2

    • DAY 1: elexacaftor 80 mg/
      tezacaftor 40 mg/
      ivacaftor 60 mg
      (1 white and blue packet)
    • DAY 2b: ivacaftor 59.5 mg
      (1 white and green packet)

    NO PACKET IN THE EVENING

    ≥14 kg (≥31 lb)1,2Strong CYP3A inducers including1: rifampin, rifabutin, phenobarbital, carbamazepine, phenytoin, St. John’s wort (Hypericum perforatum)CONCOMITANT USE 
    NOT RECOMMENDED
    Strong CYP3A inhibitors including1: ketoconazole, itraconazole, posaconazole, voriconazole, telithromycin, clarithromycin

    IN THE MORNING (TWICE A WEEK)

    • DAY 1: elexacaftor 100 mg/
      tezacaftor 50 mg/
      ivacaftor 75 mg
      (1 white and orange packet)
    • DAY 4a: elexacaftor 100 mg/
      tezacaftor 50 mg/
      ivacaftor 75 mg
      (1 white and orange packet)

    NO PACKET IN THE EVENING

    Moderate CYP3A inhibitors including1: fluconazole, erythromycin

    ALTERNATE GRANULES EVERY MORNING2

    • DAY 1: elexacaftor 100 mg/
      tezacaftor 50 mg/
      ivacaftor 75 mg
      (1 white and orange packet)
    • DAY 2b: ivacaftor 75 mg
      (1 white and pink packet)

    NO PACKET IN THE EVENING

    Weight
    <14 kg (<31 lb)1,2

    Drug Interaction Profile

    Strong CYP3A inducers including1: rifampin, rifabutin, phenobarbital, carbamazepine, phenytoin, St. John's wort (Hypericum perforatum)

    Dosing Considerations

    CONCOMITANT USE
    NOT RECOMMENDED

    Drug Interaction Profile

    Strong CYP3A inhibitors including1: ketoconazole, itraconazole, posaconazole, voriconazole, telithromycin, clarithromycin

    Dosing Considerations

    IN THE MORNING (TWICE A WEEK)

    • DAY 1: elexacaftor 80 mg/
      tezacaftor 40 mg/
      ivacaftor 60 mg
      (1 white and blue packet)
    • DAY 4a: elexacaftor 80 mg/
      tezacaftor 40 mg/
      ivacaftor 60 mg
      (1 white and blue packet)

    NO PACKET IN THE EVENING

    Drug Interaction Profile

    Moderate CYP3A inhibitors including1: 
    fluconazole, erythromycin

    Dosing Considerations

    ALTERNATE GRANULES EVERY MORNING2

    • DAY 1: elexacaftor 80 mg/
      tezacaftor 40 mg/
      ivacaftor 60 mg
      (1 white and blue packet)
    • DAY 2b: ivacaftor 59.5 mg
      (1 white and green packet)

    NO PACKET IN THE EVENING

    Weight
    ≥14 kg (≥31 lb)1,2

    Drug Interaction Profile

    Strong CYP3A inducers including1: rifampin, rifabutin, phenobarbital, carbamazepine, phenytoin, St. John's wort (Hypericum perforatum)

    Dosing Considerations

    CONCOMITANT USE
    NOT RECOMMENDED

    Drug Interaction Profile

    Strong CYP3A inhibitors including1: ketoconazole, itraconazole, posaconazole, voriconazole, telithromycin, clarithromycin

    Dosing Considerations

    IN THE MORNING (TWICE A WEEK)

    • DAY 1: elexacaftor 100 mg/
      tezacaftor 50 mg/
      ivacaftor 75 mg
      (1 white and orange packet)
    • DAY 4a: elexacaftor 100 mg/
      tezacaftor 50 mg/
      ivacaftor 75 mg
      (1 white and orange packet)

    NO PACKET IN THE EVENING

    Drug Interaction Profile

    Moderate CYP3A inhibitors including1: 
    fluconazole, erythromycin

    Dosing Considerations

    ALTERNATE GRANULES EVERY MORNING2

    • DAY 1: elexacaftor 100 mg/
      tezacaftor 50 mg/
      ivacaftor 75 mg
      (1 white and blue packet)
    • DAY 2b: ivacaftor 75 mg
      (1 white and pink packet)

    NO PACKET IN THE EVENING

    For more information about specific drug interactions and adjustment recommendations, see the Drug-Drug Interactions Tool.

    MISSED DOSE

    What to do if a dose is missed1

    MISSED MORNING DOSE

    • If ≤6 hours have passed, take as soon as possible and take evening dose as scheduled
    • If >6 hours have passed, take the missed dose as soon as possible but do not take evening dose and continue as scheduled the following day

    MISSED EVENING DOSE

    • If ≤6 hours have passed, take as soon as possible and take next morning dose as scheduled
    • If >6 hours have passed, do not take missed dose and take next morning dose as scheduled the following day
    • If ≤6 hours have passed, take as soon as possible and take evening dose as scheduled
    • If >6 hours have passed, take the missed dose as soon as possible but do not take evening dose and continue as scheduled the following day
    • If ≤6 hours have passed, take as soon as possible and take next morning dose as scheduled
    • If >6 hours have passed, do not take missed dose and take next morning dose as scheduled the following day

    Morning and evening doses should not be taken at the same time

    eGFR, estimated glomerular filtration rate; lb, pounds.

    aContinue dosing with 1 elexacaftor/tezacaftor/ivacaftor packet twice a week, approximately 3 to 4 days apart.1

    bContinue dosing with 1 elexacaftor/tezacaftor/ivacaftor packet and 1 ivacaftor packet on alternate days.1

    6 to <12 Years

    6 to <12 Years

    On this Page:
    Dosing Information Dosing Adjustments Missed Dose
    On this Page:
    Dosing Information Dosing Adjustments Missed Dose

    DOSING INFORMATION

    Recommended dosing for patients aged 6 to <12 years1

    • Laboratory testing for liver function is recommended prior to TRIKAFTA® (elexacaftor/tezacaftor/ivacaftor and ivacaftor) initiation and treatment. Please see Dosage and Administration section of the full Prescribing Information
    • TRIKAFTA should be taken with fat-containing meals or snacks. Examples include food prepared with butter or oils or those containing eggs, cheeses, nuts, whole milk, meats, or peanut butter
    • Laboratory testing for liver function is recommended prior to TRIKAFTA® (elexacaftor/tezacaftor/ivacaftor and ivacaftor) initiation and treatment. Please see Dosage and Administration section of the full Prescribing Information
    • TRIKAFTA should be taken with fat-containing meals or snacks. Examples include food prepared with butter or oils or those containing eggs, cheeses, nuts, whole milk, meats, or peanut butter
    • Morning and evening doses should be taken approximately 12 hours apart
    • Food or drink containing grapefruit should be avoided during treatment with TRIKAFTA

    For patients aged 6 to <12 years weighing <30 kg (<66 lb)1,2

    Image of TRIKAFTA in cartons for patients aged 6 through 11 years weighing <30 kg (<66 lb)

    For patients aged 6 to <12 years weighing ≥30 kg (≥66 lb)1,2

    TRIKAFTA in cartons for patients aged 6 through 11 years weighing ≥30 kg (≥66 lb)
    WeightMorning DoseEvening Dose
    <30 kg (<66 lb)1,22 light orange tablets of:
    elexacaftor 50 mg/
    tezacaftor 25 mg/
    ivacaftor 37.5 mg    		1 light blue tablet of:
    ivacaftor 75 mg
    ≥30 kg (≥66 lb)1,22 orange tablets of:
    elexacaftor 100 mg/
    tezacaftor 50 mg/
    ivacaftor 75 mg    		1 light blue tablet of:
    ivacaftor 150 mg
    Weight
    <30 kg (<66 lb)1,2
    Morning Dose
    2 light orange tablets of:
    elexacaftor 50 mg/
    tezacaftor 25 mg/
    ivacaftor 37.5 mg
    Evening Dose 
    1 light blue tablet of:
    ivacaftor 75 mg
    Weight
    ≥30 kg (≥66 lb)1,2
    Morning Dose
    2 orange tablets of:
    elexacaftor 100 mg/
    tezacaftor 50 mg/
    ivacaftor 75 mg
    Evening Dose 
    1 light blue tablet of:
    ivacaftor 150 mg
    • Elexacaftor 50 mg, tezacaftor 25 mg, and ivacaftor 37.5 mg tablets are light orange, oblong-shaped, and debossed with “T50” on one side and plain on the other
    • Ivacaftor 75 mg tablets are light blue, film-coated, oblong-shaped, and printed with “V 75” in black ink on one side and plain on the other
    • Elexacaftor 100 mg, tezacaftor 50 mg, and ivacaftor 75 mg tablets are orange, oblong-shaped, and debossed with “T100” on one side and plain on the other
    • Ivacaftor 150 mg tablets are light blue, film-coated, oblong-shaped, and printed with “V 150” in black ink on one side and plain on the other

    DOSING ADJUSTMENTS

    Dose adjustments for hepatic impairment in patients aged 6 to <12 years1

    In patients with mild hepatic impairment (Child-Pugh Class A)

    NO DOSE ADJUSTMENT

    • Liver function tests should be closely monitored1
    In patients with moderate hepatic impairment (Child-Pugh Class B)

    TREATMENT IS NOT RECOMMENDED

    USE SHOULD ONLY BE CONSIDERED WHEN THERE IS A CLEAR MEDICAL NEED AND THE BENEFITS ARE EXPECTED TO OUTWEIGH THE RISKS

    If used, TRIKAFTA should be used with caution at a reduced dose, as follows:

    • Day 1: Patients should take 2 elexacaftor/ tezacaftor/ivacaftor tablets in the morning
    • Day 2: Patients should take 1 elexacaftor/ tezacaftor/ivacaftor tablet in the morning

    Continue alternating Day 1 and Day 2 dosing thereafter No evening dose of ivacaftor should be taken

    • Liver function tests should be closely monitored1
    In patients with severe hepatic impairment (Child-Pugh Class C)

    SHOULD NOT BE USED

    • TRIKAFTA has not been studied in patients with severe hepatic impairment, but the exposure is expected to be higher than in patients with moderate hepatic impairment1
    In patients with mild hepatic impairment (Child-Pugh Class A)

    NO DOSE ADJUSTMENT

    • Liver function tests should be closely monitored1
    In patients with moderate hepatic impairment (Child-Pugh Class B)

    TREATMENT IS NOT RECOMMENDED

    USE SHOULD ONLY BE CONSIDERED WHEN THERE IS A CLEAR MEDICAL NEED AND THE BENEFITS ARE EXPECTED TO OUTWEIGH THE RISKS

    If used, TRIKAFTA should be used with caution at a reduced dose, as follows:

    • Day 1: Patients should take 2 
      elexacaftor/tezacaftor/ivacaftor tablets in the morning
    • Day 2: Patients should take 1 
      elexacaftor/tezacaftor/ivacaftor tablet in the morning

    Continue alternating Day 1 and Day 2 dosing thereafter No evening dose of ivacaftor should be taken

    • Liver function tests should be closely monitored1
    In patients with severe hepatic impairment (Child-Pugh Class C)

    SHOULD NOT BE USED

    • TRIKAFTA has not been studied in patients with severe hepatic impairment, but the exposure is expected to be higher than in patients with moderate hepatic impairment1

    Dose adjustments for renal impairment in patients aged 6 to <12 years

    • No dose adjustment is recommended in patients with mild (eGFR 60 to <90 mL/min/1.73 m2) or moderate (eGFR 30 to <60 mL/min/1.73 m2) renal impairment. TRIKAFTA has not been studied in patients with severe (eGFR <30 mL/min/1.73 m2) renal impairment or end-stage renal disease and should be used with caution in these patients1

    Drug interaction profiles and related dosing considerations for patients aged 6 to <12 years

    WeightDrug Interaction ProfileDosing Considerations
    <30 kg (<66 lb)1,2Strong CYP3A inducers including1: rifampin, rifabutin, phenobarbital, carbamazepine, phenytoin, St. John's wort (Hypericum perforatum)CONCOMITANT USE
    NOT RECOMMENDED
    Strong CYP3A inhibitors including1: ketoconazole, itraconazole, posaconazole, voriconazole, telithromycin, clarithromycin

    IN THE MORNING (TWICE A WEEK)

    • DAY 1: elexacaftor 50 mg/
      tezacaftor 25 mg/
      ivacaftor 37.5 mg
      (2 light orange tablets)
    • DAY 4c: elexacaftor 50 mg/
      tezacaftor 25 mg/
      ivacaftor 37.5 mg
      (2 light orange tablets)

    NO TABLET IN THE EVENING

    Moderate CYP3A inhibitors including1: fluconazole, erythromycin

    ALTERNATE TABLETS EVERY MORNING

    • DAY 1: elexacaftor 50 mg/
      tezacaftor 25 mg/
      ivacaftor 37.5 mg
      (2 light orange tablets)
    • DAY 2d: ivacaftor 75 mg
      (1 light blue tablet)

    NO TABLET IN THE EVENING

    ≥30 kg (≥66 lb)1,2Strong CYP3A inducers including1: rifampin, rifabutin, phenobarbital, carbamazepine, phenytoin, St. John’s wort (Hypericum perforatum)CONCOMITANT USE 
    NOT RECOMMENDED
    Strong CYP3A inhibitors including1: ketoconazole, itraconazole, posaconazole, voriconazole, telithromycin, clarithromycin

    IN THE MORNING (TWICE A WEEK)

    • DAY 1: elexacaftor 100 mg/
      tezacaftor 50 mg/
      ivacaftor 75 mg
      (2 orange tablets)
    • DAY 4c: elexacaftor 100 mg/
      tezacaftor 50 mg/
      ivacaftor 75 mg
      (2 orange tablets)

    NO TABLET IN THE EVENING

    Moderate CYP3A inhibitors including1: fluconazole, erythromycin

    ALTERNATE TABLETS EVERY MORNING2

    • DAY 1: elexacaftor 100 mg/
      tezacaftor 50 mg/
      ivacaftor 75 mg
      (2 orange tablets)
    • DAY 2d: ivacaftor 150 mg
      (1 light blue tablet)

    NO TABLET IN THE EVENING

    Weight
    <30 kg (<66 lb)1,2

    Drug Interaction Profile

    Strong CYP3A inducers including1: rifampin, rifabutin, phenobarbital, carbamazepine, phenytoin, St. John's wort (Hypericum perforatum)

    Dosing Considerations

    CONCOMITANT USE
    NOT RECOMMENDED

    Drug Interaction Profile

    Strong CYP3A inhibitors including1: ketoconazole, itraconazole, posaconazole, voriconazole, telithromycin, clarithromycin

    Dosing Considerations

    IN THE MORNING (TWICE A WEEK)

    • DAY 1: elexacaftor 50 mg/
      tezacaftor 25 mg/
      ivacaftor 37.5 mg
      (2 light orange tablets)
    • DAY 4c: elexacaftor 50 mg/
      tezacaftor 25 mg/
      ivacaftor 37.5 mg
      (2 light orange tablets)

    NO TABLET IN THE EVENING

    Drug Interaction Profile

    Moderate CYP3A inhibitors including1: 
    fluconazole, erythromycin

    Dosing Considerations

    ALTERNATE TABLETS EVERY MORNING

    • DAY 1: elexacaftor 50 mg/
      tezacaftor 25 mg/
      ivacaftor 37.5 mg
      (2 light orange tablets)
    • DAY 2d: ivacaftor 75 mg
      (1 light blue tablet)

    NO TABLET IN THE EVENING

    Weight
    ≥30 kg (≥66 lb)1,2

    Drug Interaction Profile

    Strong CYP3A inducers including1: rifampin, rifabutin, phenobarbital, carbamazepine, phenytoin, St. John's wort (Hypericum perforatum)

    Dosing Considerations

    CONCOMITANT USE
    NOT RECOMMENDED

    Drug Interaction Profile

    Strong CYP3A inhibitors including1: ketoconazole, itraconazole, posaconazole, voriconazole, telithromycin, clarithromycin

    Dosing Considerations

    IN THE MORNING (TWICE A WEEK)2

    • DAY 1: elexacaftor 100 mg/
      tezacaftor 50 mg/
      ivacaftor 75 mg
      (2 orange tablets)
    • DAY 4c: elexacaftor 100 mg/
      tezacaftor 50 mg/
      ivacaftor 75 mg
      (2 orange tablets)

    NO TABLET IN THE EVENING

    Drug Interaction Profile

    Moderate CYP3A inhibitors including1: 
    fluconazole, erythromycin

    Dosing Considerations

    ALTERNATE TABLETS EVERY MORNING2

    • DAY 1: elexacaftor 100 mg/
      tezacaftor 50 mg/
      ivacaftor 75 mg
      (2 orange tablets)
    • DAY 2d: ivacaftor 150 mg
      (1 light blue tablet)

    NO TABLET IN THE EVENING

    For more information about specific drug interactions and adjustment recommendations, see the Drug-Drug Interactions Tool.

    MISSED DOSE

    What to do if a dose is missed1

    MISSED MORNING DOSE

    • If ≤6 hours have passed, take as soon as possible and take evening dose as scheduled
    • If >6 hours have passed, take the missed dose as soon as possible but do not take evening dose and continue as scheduled the following day

    MISSED EVENING DOSE

    • If ≤6 hours have passed, take as soon as possible and take next morning dose as scheduled
    • If >6 hours have passed, do not take missed dose and take next morning dose as scheduled the following day
    • If ≤6 hours have passed, take as soon as possible and take evening dose as scheduled
    • If >6 hours have passed, take the missed dose as soon as possible but do not take evening dose and continue as scheduled the following day
    • If ≤6 hours have passed, take as soon as possible and take next morning dose as scheduled
    • If >6 hours have passed, do not take missed dose and take next morning dose as scheduled the following day

    Morning and evening doses should not be taken at the same time

    eGFR, estimated glomerular filtration rate; lb, pounds.

    cContinue dosing with 2 elexacaftor/tezacaftor/ivacaftor tablets twice a week, approximately 3 to 4 days apart.1

    dContinue dosing with 2 elexacaftor/tezacaftor/ivacaftor tablets and 1 ivacaftor tablet on alternate days.1

    12 Years and Older

    On this Page:
    Dosing Information Dosing Adjustments Missed Dose
    On this Page:
    Dosing Information Dosing Adjustments Missed Dose

    DOSING INFORMATION

    Recommended dosing for patients aged 12 years and older1

    • Laboratory testing for liver function is recommended prior to TRIKAFTA® (elexacaftor/tezacaftor/ivacaftor and ivacaftor) initiation and treatment. Please see Dosage and Administration section of the full Prescribing Information
    • TRIKAFTA should be taken with fat-containing meals or snacks. Examples include food prepared with butter or oils or those containing eggs, cheeses, nuts, whole milk, meats, or peanut butter
    • Laboratory testing for liver function is recommended prior to TRIKAFTA® (elexacaftor/tezacaftor/ivacaftor and ivacaftor) initiation and treatment. Please see Dosage and Administration section of the full Prescribing Information
    • TRIKAFTA should be taken with fat-containing meals or snacks. Examples include food prepared with butter or oils or those containing eggs, cheeses, nuts, whole milk, meats, or peanut butter
    • Morning and evening doses should be taken approximately 12 hours apart
    • Food or drink containing grapefruit should be avoided during treatment with TRIKAFTA

    For patients aged 12 years and older1

    TRIKAFTA in cartons for patients aged 12 years and older TRIKAFTA in cartons for patients aged 12 years and older

    Not actual size.

    Morning Dose Evening Dose 
    2 orange tablets of:
    elexacaftor 100 mg/
    tezacaftor 50 mg/
    ivacaftor 75 mg    		1 light blue tablet of:
    ivacaftor 150 mg
    Morning Dose 
    2 orange tablets of:
    elexacaftor 100 mg/
    tezacaftor 50 mg/
    ivacaftor 75 mg
    Evening Dose 
    1 light blue tablet of:
    ivacaftor 150 mg
    • Elexacaftor, tezacaftor, and ivacaftor tablets are orange, oblong-shaped, and debossed with “T100” on one side and plain on the other
    • Ivacaftor tablets are light blue, film-coated, oblong-shaped, and printed with “V 150” in black ink on one side and plain on the other

    DOSING ADJUSTMENTS

    Dose adjustments for hepatic impairment in patients aged 12 years and older1

    In patients with mild hepatic impairment (Child-Pugh Class A)

    NO DOSE ADJUSTMENT

    • Liver function tests should be closely monitored1
    In patients with moderate hepatic impairment (Child-Pugh Class B)

    TREATMENT IS NOT RECOMMENDED

    USE SHOULD ONLY BE CONSIDERED WHEN THERE IS A CLEAR MEDICAL NEED AND THE BENEFITS ARE EXPECTED TO OUTWEIGH THE RISKS

    If used, TRIKAFTA should be used with caution at a reduced dose, as follows:

    • Day 1: Patients should take 2 elexacaftor/ tezacaftor/ivacaftor tablets in the morning
    • Day 2: Patients should take 1 elexacaftor/ tezacaftor/ivacaftor tablet in the morning

    Continue alternating Day 1 and Day 2 dosing thereafter No evening dose of ivacaftor should be taken

    • Liver function tests should be closely monitored1
    In patients with severe hepatic impairment (Child-Pugh Class C)

    SHOULD NOT BE USED

    • TRIKAFTA has not been studied in patients with severe hepatic impairment, but the exposure is expected to be higher than in patients with moderate hepatic impairment1
    In patients with mild hepatic impairment (Child-Pugh Class A)

    NO DOSE ADJUSTMENT

    • Liver function tests should be closely monitored1
    In patients with moderate hepatic impairment (Child-Pugh Class B)

    TREATMENT IS NOT RECOMMENDED

    USE SHOULD ONLY BE CONSIDERED WHEN THERE IS A CLEAR MEDICAL NEED AND THE BENEFITS ARE EXPECTED TO OUTWEIGH THE RISKS

    If used, TRIKAFTA should be used with caution at a reduced dose, as follows:

    • Day 1: Patients should take 2 
      elexacaftor/tezacaftor/ivacaftor tablets in the morning
    • Day 2: Patients should take 1 
      elexacaftor/tezacaftor/ivacaftor tablet in the morning

    Continue alternating Day 1 and Day 2 dosing thereafter No evening dose of ivacaftor should be taken

    • Liver function tests should be closely monitored1
    In patients with severe hepatic impairment (Child-Pugh Class C)

    SHOULD NOT BE USED

    • TRIKAFTA has not been studied in patients with severe hepatic impairment, but the exposure is expected to be higher than in patients with moderate hepatic impairment1

    Dose adjustments for renal impairment in patients aged 12 years and older

    • No dose adjustment is recommended in patients with mild (eGFR 60 to <90 mL/min/1.73 m2) or moderate (eGFR 30 to <60 mL/min/1.73 m2) renal impairment. TRIKAFTA has not been studied in patients with severe (eGFR <30 mL/min/1.73 m2) renal impairment or end-stage renal disease and should be used with caution in these patients1

    Drug interaction profiles and related dosing considerations for patients aged 12 years and older

    Drug Interaction ProfileDosing Considerations
    Strong CYP3A inducers including1:
    rifampin, rifabutin, phenobarbital,
    carbamazepine, phenytoin, St. John's
    wort (Hypericum perforatum)

    CONCOMITANT USE
    NOT RECOMMENDED

    Strong CYP3A inhibitors including1:
    ketoconazole, itraconazole,
    posaconazole, voriconazole,
    telithromycin, clarithromycin

    IN THE MORNING (TWICE A WEEK)

    • DAY 1: elexacaftor 100 mg/
      tezacaftor 50 mg/
      ivacaftor 75 mg
      (2 orange tablets)
    • DAY 4c: elexacaftor 100 mg/
      tezacaftor 50 mg/
      ivacaftor 75 mg
      (2 orange tablets)

    NO TABLET IN THE EVENING

    Moderate CYP3A inhibitors including1:
    fluconazole, erythromycin

    ALTERNATE TABLETS EVERY MORNING

    • DAY 1: elexacaftor 100 mg/
      tezacaftor 50 mg/
      ivacaftor 75 mg
      (2 orange tablets)
    • DAY 2d: ivacaftor 150 mg
      (1 light blue tablet)

    NO TABLET IN THE EVENING

    Drug Interaction Profile

    Strong CYP3A inducers including1: rifampin, rifabutin, phenobarbital, carbamazepine, phenytoin, St. John's wort (Hypericum perforatum)

    Dosing Considerations

    CONCOMITANT USE
    NOT RECOMMENDED

    Drug Interaction Profile

    Strong CYP3A inhibitors including1: ketoconazole, itraconazole, posaconazole, voriconazole, telithromycin, clarithromycin

    Dosing Considerations

    IN THE MORNING (TWICE A WEEK)

    • DAY 1: elexacaftor 50 mg/
      tezacaftor 25 mg/
      ivacaftor 37.5 mg
      (2 orange tablets)
    • DAY 4c: elexacaftor 50 mg/
      tezacaftor 25 mg/
      ivacaftor 37.5 mg
      (2 orange tablets)

    NO TABLET IN THE EVENING

    Drug Interaction Profile

    Moderate CYP3A inhibitors including1: 
    fluconazole, erythromycin

    Dosing Considerations

    ALTERNATE TABLETS EVERY MORNING

    • DAY 1: elexacaftor 50 mg/
      tezacaftor 25 mg/
      ivacaftor 37.5 mg
      (2 orange tablets)
    • DAY 2d: ivacaftor 75 mg
      (1 light blue tablet)

    NO TABLET IN THE EVENING

    For more information about specific drug interactions and adjustment recommendations, see the Drug-Drug Interactions Tool.

    MISSED DOSE

    What to do if a dose is missed1

    MISSED MORNING DOSE

    • If ≤6 hours have passed, take as soon as possible and take evening dose as scheduled
    • If >6 hours have passed, take the missed dose as soon as possible but do not take evening dose and continue as scheduled the following day

    MISSED EVENING DOSE

    • If ≤6 hours have passed, take as soon as possible and take next morning dose as scheduled
    • If >6 hours have passed, do not take missed dose and take next morning dose as scheduled the following day
    • If ≤6 hours have passed, take as soon as possible and take evening dose as scheduled
    • If >6 hours have passed, take the missed dose as soon as possible but do not take evening dose and continue as scheduled the following day
    • If ≤6 hours have passed, take as soon as possible and take next morning dose as scheduled
    • If >6 hours have passed, do not take missed dose and take next morning dose as scheduled the following day

    Morning and evening doses should not be taken at the same time

    eGFR, estimated glomerular filtration rate; lb, pounds.

    cContinue dosing with 2 elexacaftor/tezacaftor/ivacaftor tablets twice a week, approximately 3 to 4 days apart.1

    dContinue dosing with 2 elexacaftor/tezacaftor/ivacaftor tablets and 1 ivacaftor tablet on alternate days.1

    See potential drug-drug interactions

    View clinical trials of TRIKAFTA

    IMPORTANT SAFETY INFORMATION

    WARNING: DRUG-INDUCED LIVER INJURY AND LIVER FAILURE

    • TRIKAFTA can cause serious and potentially fatal drug-induced liver injury. Cases of liver failure leading to transplantation and death have been reported in patients with and without a history of liver disease taking TRIKAFTA, in both clinical trials and the postmarketing setting. Liver injury has been reported within the first month of therapy and up to 15 months following initiation of TRIKAFTA.
    • Assess liver function tests (ALT, AST, alkaline phosphatase, and bilirubin) in all patients prior to initiating TRIKAFTA, then every month during the first 6 months of treatment, every 3 months for the next 12 months, and at least annually thereafter. Consider more frequent monitoring for patients with a history of liver disease or liver function test (LFT) elevations at baseline.
    • Interrupt TRIKAFTA for significant elevations in LFTs or in the event of signs or symptoms of liver injury. Consider referral to a hepatologist. Follow patients closely with clinical and laboratory monitoring until abnormalities resolve. If resolved, resume treatment only if benefit is expected to outweigh risk. Closer monitoring is advised after resuming TRIKAFTA.
    • TRIKAFTA should not be used in patients with severe hepatic impairment (Child-Pugh Class C). TRIKAFTA is not recommended in patients with moderate hepatic impairment (Child-Pugh Class B). If used, use with caution at a reduced dosage and monitor patients closely.

    INDICATIONS AND USAGE

    TRIKAFTA is indicated for the treatment of cystic fibrosis (CF) in patients aged 2 years and 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 clinical and/or in vitro data.

    If the patient’s genotype is unknown, an FDA-cleared CF mutation test should be used to confirm the presence of at least one indicated mutation.

    WARNINGS AND PRECAUTIONS

    Drug-Induced Liver Injury and Liver Failure

    • TRIKAFTA can cause serious and potentially fatal drug-induced liver injury. Liver failure leading to transplantation and death has been reported in patients with and without a history of liver disease taking TRIKAFTA. Liver injury has been reported within the first month of therapy and up to 15 months following initiation of TRIKAFTA
    • Assess LFTs (ALT, AST, alkaline phosphatase, and bilirubin) in all patients prior to initiating TRIKAFTA, then every month during the first 6 months of treatment, every 3 months for the next 12 months, and at least annually thereafter. Consider more frequent monitoring for patients with a history of liver disease or LFT elevations at baseline
    • Interrupt TRIKAFTA in the event of signs or symptoms of liver injury, which may include:
      • Significant elevations in LFTs (e.g., ALT or AST >5x the upper limit of normal (ULN) or ALT or AST >3x ULN with bilirubin >2x ULN)
      • Clinical symptoms suggestive of liver injury (e.g., jaundice, right upper quadrant pain, nausea, vomiting, altered mental status, ascites)
    • Consider referral to a hepatologist and follow patients closely with clinical and laboratory monitoring until abnormalities resolve. If resolved, and if benefit is expected to outweigh risk, resume TRIKAFTA with close monitoring
    • TRIKAFTA should not be used in patients with severe hepatic impairment. TRIKAFTA is not recommended in patients with moderate hepatic impairment and should only be considered when there is a clear medical need and benefit outweighs risk. If used, use with caution at a reduced dosage and monitor patients closely

    Hypersensitivity Reactions, Including Anaphylaxis

    • Hypersensitivity reactions, including cases of angioedema and anaphylaxis, have been reported in the postmarketing setting. If signs or symptoms of serious hypersensitivity reactions develop during treatment, discontinue TRIKAFTA and institute appropriate therapy. Consider benefits and risks for the individual patient to determine whether to resume treatment with TRIKAFTA

    Concomitant Use With CYP3A Inducers

    • Exposure to ivacaftor is significantly decreased and exposure to elexacaftor and tezacaftor are expected to decrease by concomitant use of strong CYP3A inducers, which may reduce therapeutic effectiveness of TRIKAFTA. Concomitant use with strong CYP3A inducers is not recommended

    Concomitant Use With CYP3A Inhibitors

    • Exposure to elexacaftor, tezacaftor, and ivacaftor are increased when used concomitantly with strong or moderate CYP3A inhibitors. The dose of TRIKAFTA should be reduced when used concomitantly with moderate or strong CYP3A inhibitors

    Cataracts

    • Non-congenital lens opacities have been reported in pediatric patients treated with ivacaftor-containing regimens. Baseline and follow‑up ophthalmological examinations are recommended in pediatric patients initiating treatment with TRIKAFTA

    ADVERSE REACTIONS

    Serious Adverse Reactions

    • Serious adverse reactions that occurred more frequently in patients treated with TRIKAFTA compared to placebo were rash (1% vs <1%) and influenza (1% vs 0%)

    Most Common Adverse Reactions

    • The most common adverse reactions occurring in ≥5% of patients treated with TRIKAFTA and higher than placebo by ≥1% were headache, upper respiratory tract infection, abdominal pain, diarrhea, rash, alanine aminotransferase increased, nasal congestion, blood creatine phosphokinase increased, aspartate aminotransferase increased, rhinorrhea, rhinitis, influenza, sinusitis, blood bilirubin increased and constipation

    USE IN SPECIFIC POPULATIONS

    Pediatric Use

    • The safety and effectiveness of TRIKAFTA in patients with CF younger than 2 years of age have not been established

    Please see full Prescribing Information, including Boxed WARNING.

    References:
    1. TRIKAFTA [prescribing information]. Boston, MA: Vertex Pharmaceuticals Incorporated; December 2024. 2. Data on file. Vertex Pharmaceuticals Incorporated. Boston, MA. REF-6607 (v2.0); 2021.

     

    Indication and Important Safety Information, including Boxed WARNING

    EXPAND

    COLLAPSE

    INDICATIONS AND USAGE

    TRIKAFTA is indicated for the treatment of cystic fibrosis (CF) in patients aged 2 years and 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 clinical and/or in vitro data.

    If the patient’s genotype is unknown, an FDA-cleared CF mutation test should be used to confirm the presence of at least one indicated mutation.

    INDICATIONS AND USAGE

    TRIKAFTA is indicated for the treatment of cystic fibrosis (CF) in patients aged 2 years and 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 clinical and/or in vitro data.

    If the patient’s genotype is unknown, an FDA-cleared CF mutation test should be used to confirm the presence of at least one indicated mutation.

    IMPORTANT SAFETY INFORMATION

    WARNING: DRUG-INDUCED LIVER INJURY AND LIVER FAILURE

    • TRIKAFTA can cause serious and potentially fatal drug-induced liver injury. Cases of liver failure leading to transplantation and death have been reported in patients with and without a history of liver disease taking TRIKAFTA, in both clinical trials and the postmarketing setting. Liver injury has been reported within the first month of therapy and up to 15 months following initiation of TRIKAFTA.
    • Assess liver function tests (ALT, AST, alkaline phosphatase, and bilirubin) in all patients prior to initiating TRIKAFTA, then every month during the first 6 months of treatment, every 3 months for the next 12 months, and at least annually thereafter. Consider more frequent monitoring for patients with a history of liver disease or liver function test (LFT) elevations at baseline.
    • Interrupt TRIKAFTA for significant elevations in LFTs or in the event of signs or symptoms of liver injury. Consider referral to a hepatologist. Follow patients closely with clinical and laboratory monitoring until abnormalities resolve. If resolved, resume treatment only if benefit is expected to outweigh risk. Closer monitoring is advised after resuming TRIKAFTA.
    • TRIKAFTA should not be used in patients with severe hepatic impairment (Child-Pugh Class C). TRIKAFTA is not recommended in patients with moderate hepatic impairment (Child-Pugh Class B). If used, use with caution at a reduced dosage and monitor patients closely.

    INDICATIONS AND USAGE

    TRIKAFTA is indicated for the treatment of cystic fibrosis (CF) in patients aged 2 years and 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 clinical and/or in vitro data.

    If the patient’s genotype is unknown, an FDA-cleared CF mutation test should be used to confirm the presence of at least one indicated mutation.

    IMPORTANT SAFETY INFORMATION

    WARNING: DRUG-INDUCED LIVER INJURY AND LIVER FAILURE

    • TRIKAFTA can cause serious and potentially fatal drug-induced liver injury. Cases of liver failure leading to transplantation and death have been reported in patients with and without a history of liver disease taking TRIKAFTA, in both clinical trials and the postmarketing setting. Liver injury has been reported within the first month of therapy and up to 15 months following initiation of TRIKAFTA.
    • Assess liver function tests (ALT, AST, alkaline phosphatase, and bilirubin) in all patients prior to initiating TRIKAFTA, then every month during the first 6 months of treatment, every 3 months for the next 12 months, and at least annually thereafter. Consider more frequent monitoring for patients with a history of liver disease or liver function test (LFT) elevations at baseline.
    • Interrupt TRIKAFTA for significant elevations in LFTs or in the event of signs or symptoms of liver injury. Consider referral to a hepatologist. Follow patients closely with clinical and laboratory monitoring until abnormalities resolve. If resolved, resume treatment only if benefit is expected to outweigh risk. Closer monitoring is advised after resuming TRIKAFTA.
    • TRIKAFTA should not be used in patients with severe hepatic impairment (Child-Pugh Class C). TRIKAFTA is not recommended in patients with moderate hepatic impairment (Child-Pugh Class B). If used, use with caution at a reduced dosage and monitor patients closely.

    WARNINGS AND PRECAUTIONS

    Drug-Induced Liver Injury and Liver Failure

    • TRIKAFTA can cause serious and potentially fatal drug-induced liver injury. Liver failure leading to transplantation and death has been reported in patients with and without a history of liver disease taking TRIKAFTA. Liver injury has been reported within the first month of therapy and up to 15 months following initiation of TRIKAFTA
    • Assess LFTs (ALT, AST, alkaline phosphatase, and bilirubin) in all patients prior to initiating TRIKAFTA, then every month during the first 6 months of treatment, every 3 months for the next 12 months, and at least annually thereafter. Consider more frequent monitoring for patients with a history of liver disease or LFT elevations at baseline
    • Interrupt TRIKAFTA in the event of signs or symptoms of liver injury, which may include:
      • Significant elevations in LFTs (e.g., ALT or AST >5x the upper limit of normal (ULN) or ALT or AST >3x ULN with bilirubin >2x ULN)
      • Clinical symptoms suggestive of liver injury (e.g., jaundice, right upper quadrant pain, nausea, vomiting, altered mental status, ascites)
    • Consider referral to a hepatologist and follow patients closely with clinical and laboratory monitoring until abnormalities resolve. If resolved, and if benefit is expected to outweigh risk, resume TRIKAFTA with close monitoring
    • TRIKAFTA should not be used in patients with severe hepatic impairment. TRIKAFTA is not recommended in patients with moderate hepatic impairment and should only be considered when there is a clear medical need and benefit outweighs risk. If used, use with caution at a reduced dosage and monitor patients closely

    Hypersensitivity Reactions, Including Anaphylaxis

    • Hypersensitivity reactions, including cases of angioedema and anaphylaxis, have been reported in the postmarketing setting. If signs or symptoms of serious hypersensitivity reactions develop during treatment, discontinue TRIKAFTA and institute appropriate therapy. Consider benefits and risks for the individual patient to determine whether to resume treatment with TRIKAFTA

    Concomitant Use With CYP3A Inducers

    • Exposure to ivacaftor is significantly decreased and exposure to elexacaftor and tezacaftor are expected to decrease by concomitant use of strong CYP3A inducers, which may reduce therapeutic effectiveness of TRIKAFTA. Concomitant use with strong CYP3A inducers is not recommended

    Concomitant Use With CYP3A Inhibitors

    • Exposure to elexacaftor, tezacaftor, and ivacaftor are increased when used concomitantly with strong or moderate CYP3A inhibitors. The dose of TRIKAFTA should be reduced when used concomitantly with moderate or strong CYP3A inhibitors

    Cataracts

    • Non-congenital lens opacities have been reported in pediatric patients treated with ivacaftor-containing regimens. Baseline and follow‑up ophthalmological examinations are recommended in pediatric patients initiating treatment with TRIKAFTA

    ADVERSE REACTIONS

    Serious Adverse Reactions

    • Serious adverse reactions that occurred more frequently in patients treated with TRIKAFTA compared to placebo were rash (1% vs <1%) and influenza (1% vs 0%)

    Most Common Adverse Reactions

    • The most common adverse reactions occurring in ≥5% of patients treated with TRIKAFTA and higher than placebo by ≥1% were headache, upper respiratory tract infection, abdominal pain, diarrhea, rash, alanine aminotransferase increased, nasal congestion, blood creatine phosphokinase increased, aspartate aminotransferase increased, rhinorrhea, rhinitis, influenza, sinusitis, blood bilirubin increased and constipation

    USE IN SPECIFIC POPULATIONS

    Pediatric Use

    • The safety and effectiveness of TRIKAFTA in patients with CF younger than 2 years of age have not been established

    Please see full Prescribing Information, including Boxed WARNING.

    References:
    1. TRIKAFTA [prescribing information]. Boston, MA: Vertex Pharmaceuticals Incorporated; December 2024. 2. Data on file. Vertex Pharmaceuticals Incorporated. Boston, MA. REF-6607 (v2.0); 2021.

     

    WARNINGS AND PRECAUTIONS

    Drug-Induced Liver Injury and Liver Failure

    • TRIKAFTA can cause serious and potentially fatal drug-induced liver injury. Liver failure leading to transplantation and death has been reported in patients with and without a history of liver disease taking TRIKAFTA. Liver injury has been reported within the first month of therapy and up to 15 months following initiation of TRIKAFTA
    • Assess LFTs (ALT, AST, alkaline phosphatase, and bilirubin) in all patients prior to initiating TRIKAFTA, then every month during the first 6 months of treatment, every 3 months for the next 12 months, and at least annually thereafter. Consider more frequent monitoring for patients with a history of liver disease or LFT elevations at baseline
    • Interrupt TRIKAFTA in the event of signs or symptoms of liver injury, which may include:
      • Significant elevations in LFTs (e.g., ALT or AST >5x the upper limit of normal (ULN) or ALT or AST >3x ULN with bilirubin >2x ULN)
      • Clinical symptoms suggestive of liver injury (e.g., jaundice, right upper quadrant pain, nausea, vomiting, altered mental status, ascites)
    • Consider referral to a hepatologist and follow patients closely with clinical and laboratory monitoring until abnormalities resolve. If resolved, and if benefit is expected to outweigh risk, resume TRIKAFTA with close monitoring
    • TRIKAFTA should not be used in patients with severe hepatic impairment. TRIKAFTA is not recommended in patients with moderate hepatic impairment and should only be considered when there is a clear medical need and benefit outweighs risk. If used, use with caution at a reduced dosage and monitor patients closely

    Hypersensitivity Reactions, Including Anaphylaxis

    • Hypersensitivity reactions, including cases of angioedema and anaphylaxis, have been reported in the postmarketing setting. If signs or symptoms of serious hypersensitivity reactions develop during treatment, discontinue TRIKAFTA and institute appropriate therapy. Consider benefits and risks for the individual patient to determine whether to resume treatment with TRIKAFTA

    Concomitant Use With CYP3A Inducers

    • Exposure to ivacaftor is significantly decreased and exposure to elexacaftor and tezacaftor are expected to decrease by concomitant use of strong CYP3A inducers, which may reduce therapeutic effectiveness of TRIKAFTA. Concomitant use with strong CYP3A inducers is not recommended

    Concomitant Use With CYP3A Inhibitors

    • Exposure to elexacaftor, tezacaftor, and ivacaftor are increased when used concomitantly with strong or moderate CYP3A inhibitors. The dose of TRIKAFTA should be reduced when used concomitantly with moderate or strong CYP3A inhibitors

    Cataracts

    • Non-congenital lens opacities have been reported in pediatric patients treated with ivacaftor-containing regimens. Baseline and follow‑up ophthalmological examinations are recommended in pediatric patients initiating treatment with TRIKAFTA

    ADVERSE REACTIONS

    Serious Adverse Reactions

    • Serious adverse reactions that occurred more frequently in patients treated with TRIKAFTA compared to placebo were rash (1% vs <1%) and influenza (1% vs 0%)

    Most Common Adverse Reactions

    • The most common adverse reactions occurring in ≥5% of patients treated with TRIKAFTA and higher than placebo by ≥1% were headache, upper respiratory tract infection, abdominal pain, diarrhea, rash, alanine aminotransferase increased, nasal congestion, blood creatine phosphokinase increased, aspartate aminotransferase increased, rhinorrhea, rhinitis, influenza, sinusitis, blood bilirubin increased and constipation

    USE IN SPECIFIC POPULATIONS

    Pediatric Use

    • The safety and effectiveness of TRIKAFTA in patients with CF younger than 2 years of age have not been established

    Please see full Prescribing Information, including Boxed WARNING.

    References:
    1. TRIKAFTA [prescribing information]. Boston, MA: Vertex Pharmaceuticals Incorporated; December 2024. 2. Data on file. Vertex Pharmaceuticals Incorporated. Boston, MA. REF-6607 (v2.0); 2021.