DOSING AND ADMINISTRATION1,2
Dosing information
- For oral use. Patients should be instructed to swallow the tablets whole
- TRIKAFTA® (elexacaftor/tezacaftor/ivacaftor and ivacaftor) 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, or meats
- Food or drink containing grapefruit should be avoided during treatment with TRIKAFTA
 MORNING |
 EVENING |
|
|---|---|---|
| Patients aged 6 through 11 years weighing <30 kg (<66 lb) | ||
| RECOMMENDED DOSAGE |
 elexacaftor 50 mg/
tezacaftor 25 mg/ ivacaftor 37.5 mg/ 2 light orange tablets |
 ivacaftor 75 mg
1 light blue tablet |
| Patients aged 6 through 11 years weighing ≥30 kg (≥66 lb) and 12 years and older | ||
| RECOMMENDED DOSAGE |
 elexacaftor 100 mg/
tezacaftor 50 mg/ ivacaftor 75 mg 2 orange tablets |
 ivacaftor 150 mg
1 light blue tablet |
| In patients with severe hepatic impairment (Child-Pugh Class C) |
SHOULD NOT BE USED |
|
| In patients with moderate hepatic impairment (Child-Pugh Class B) |
USE SHOULD ONLY BE CONSIDERED WHEN THERE IS |
|
| Strong CYP3A inducers including: rifampin, rifabutin, phenobarbital, carbamazepine, phenytoin, St. John’s wort ( Hypericum perforatum) | CONCOMITANT USE NOT RECOMMENDED |
|
| Strong CYP3A inhibitors including: ketoconazole, itraconazole, posaconazole, voriconazole, telithromycin, clarithromycin |
For patients aged 6 through 11 years weighing <30 kg (<66 lb)
IN THE MORNING (TWICE A WEEK)
DAY 1 tezacaftor 25 mg/ ivacaftor 37.5 mg 2 light orange tablets DAY 4c tezacaftor 25 mg/ ivacaftor 37.5 mg 2 light orange tablets For patients aged 6 through 11 years weighing ≥30 kg (≥66 lb) and 12 years and older
IN THE MORNING (TWICE A WEEK)
 DAY 1 2 orange tablets DAY 4c 2 orange tablets |
NO TABLET IN THE EVENING |
| Moderate CYP3A inhibitors including: fluconazole, erythromycin |
For patients aged 6 through 11 years weighing <30 kg (<66 lb)
ALTERNATE TABLETS EVERY MORNING
DAY 1 2 light orange tablets DAY 2d ivacaftor 75 mg For patients aged 6 through 11 years weighing ≥30 kg (≥66 lb) and 12 years and older
ALTERNATE TABLETS EVERY MORNING
DAY 1 2 orange tablets  DAY 2d ivacaftor 150 mg |
NO TABLET IN THE EVENING |
 MORNING |  EVENING |
| Patients aged 6 through 11 years weighing <30 kg (<66 lb) | |
| RECOMMENDED DOSAGE | |
elexacaftor 50 mg/ | ivacaftor 75 mg |
| Patients aged 6 through 11 years weighing ≥30 kg (≥66 lb) and 12 years and older | |
| RECOMMENDED DOSAGE | |
 elexacaftor 100 mg/ |  ivacaftor 150 mg |
| In patients with severe hepatic impairment (Child-Pugh Class C) | |
| SHOULD NOT BE USED | |
| |
| In patients moderate hepatic impairment (Child-Pugh Class B) | |
| USE SHOULD ONLY BE CONSIDERED WHEN THERE IS A CLEAR MEDICAL NEED AND THE BENEFIT EXCEEDS THE RISKa,b | |
| |
| Strong CYP3A inducers including: rifampin, rifabutin, phenobarbital, carbamazepine, phenytoin, St. John’s wort (Hypericum perforatum) | |
| CONCOMMITANT USE NOT RECOMMENDED | |
| |
| Strong CYP3A inhibitors including: ketoconazole, itraconazole, posaconazole, voriconazole, telithromycin, clarithromycin | |
For patients aged 6 through 11 years weighing <30 kg (<66 lb)
DAY 1 elexacaftor 50 mg/ DAY 4c elexacaftor 50 mg/ For patients aged 6 through 11 years weighing ≥30 kg (≥66 lb) and 12 years and older IN THE MORNING (TWICE A WEEK)  DAY 1 elexacaftor 100 mg/  DAY 4c elexacaftor 100 mg/ | NO TABLET IN THE EVENING |
| |
| Moderate CYP3A inhibitors including: fluconazole, erythromycin | |
For patients aged 6 through 11 years weighing <30 kg (<66 lb) ALTERNATE TABLETS EVERY MORNING DAY 1 elexacaftor 50 mg/
DAY 2d ivacaftor 75 mg For patients aged 6 through 11 years weighing ≥30 kg (≥66 lb) and and older
 DAY 1 elexacaftor 100 mg/ DAY 2d ivacaftor 150 mg | NO TABLET IN THE EVENING |
|
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MORNING
|
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Tablets are not actual size.
ᵃLiver function tests should be closely monitored.¹
aLiver function tests should be closely monitored.1
ᵃLiver function tests should be closely monitored.¹
bTRIKAFTA is not recommended for patients with moderate hepatic impairment. If TRIKAFTA is used in patients with moderate hepatic impairment, it should be with caution and at a reduced dose, as follows1:
- 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
- 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
- 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
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
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
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
- No dose adjustment is required for patients with mild hepatic impairment. Liver function tests should be closely monitored¹
- 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 impairment. TRIKAFTA should not be used in patients with severe hepatic impairment¹
- No dose adjustment is recommended in patients with mild or moderate renal impairment TRIKAFTA has not been studied in patients with severe renal impairment or end stage renal disease and should be used with caution in these patients¹
- No dose adjustment is required for patients with mild hepatic impairment. Liver function tests should be closely monitored1
- 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 impairment. TRIKAFTA should not be used in patients with severe hepatic impairment1 - No dose adjustment is recommended in patients with mild or moderate renal impairment TRIKAFTA has not been studied in patients with severe renal impairment or end stage renal disease and should be used with caution in these patients1
- No dose adjustment is required for patients with mild hepatic impairment. Liver function tests should be closely monitored1
- 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 impairment.
TRIKAFTA should not be used in patients with severe hepatic impairment1 - No dose adjustment is recommended in patients with mild or moderate renal impairment
TRIKAFTA has not been studied in patients with severe renal impairment or end stage renal
disease and should be used with caution in these patients1
MISSED DOSE1
MISSED MORNING DOSE
MISSED EVENING DOSE
Morning and evening doses should not be taken at the same time
MISSED DOSE1
MISSED DOSE1
MISSED MORNING DOSE
MISSED EVENING DOSE
Morning and evening doses should not be taken at the same time
TRIKAFTA is supplied in cartons containing 4 weekly wallets, each with 21 tablets1,2
For patients aged 6 through 11 years weighing <30 kg (<66 lb)
For patients aged 6 through
11 years weighing <30 kg (<66 lb)
Not actual size.
- TRIKAFTA is a co-package of fixed-dose combination tablets containing elexacaftor
50 mg, tezacaftor 25 mg, and ivacaftor 37.5 mg, and ivacaftor 75 mg tablets- The elexacaftor, tezacaftor, and ivacaftor tablets are light orange, capsule-shaped, and debossed with "T50" on one side and plain on the other
- The ivacaftor tablets are light blue, capsule-shaped, and printed with "V 75" in black ink on one side and plain on the other
For patients aged 6 through 11 years weighing <30 kg (<66 lb)
For patients aged 6 through
11 years weighing <30 kg (<66 lb)
Not actual size.
- TRIKAFTA is a co-package of fixed-dose combination tablets containing elexacaftor
50 mg, tezacaftor 25 mg, and ivacaftor 37.5 mg, and ivacaftor 75 mg tablets- The elexacaftor, tezacaftor, and ivacaftor tablets are light orange, capsule-shaped, and debossed with "T50" on one side and plain on the other
- The ivacaftor tablets are light blue, capsule-shaped, and printed with "V 75" in black ink on one side and plain on the other
For patients aged 6 through 11 years weighing ≥30 kg (≥66 lb) and 12 years and older
For patients aged 6 through
11 years weighing ≥30 kg (≥66 lb) and
12 years and older
Not actual size.
- TRIKAFTA is a co-package of fixed-dose combination tablets containing elexacaftor 100 mg, tezacaftor 50 mg, and ivacaftor 75 mg, and ivacaftor 150 mg tablets
- The elexacaftor, tezacaftor, and ivacaftor tablets are orange, capsule-shaped, and debossed with "T100" on one side and plain on the other
- The ivacaftor tablets are light blue, capsule-shaped, and printed with "V 150" in black ink on one side and plain on the other
For patients aged 6 through 11 years weighing ≥30 kg (≥66 lb) and 12 years and older
For patients aged 6 through
11 years weighing ≥30 kg (≥66 lb) and
12 years and older
Not actual size.
- TRIKAFTA is a co-package of fixed-dose combination tablets containing elexacaftor 100 mg, tezacaftor 50 mg, and ivacaftor 75 mg, and ivacaftor 150 mg tablets
- The elexacaftor, tezacaftor, and ivacaftor tablets are orange, capsule-shaped, and debossed with "T100" on one side and plain on the other
- The ivacaftor tablets are light blue, capsule-shaped, and printed with "V 150" in black ink on one side and plain on the other
lb, pounds.
Important Safety Information
Elevated Transaminases and Hepatic Injury
- Liver failure leading to transplantation has been reported in a patient with cirrhosis and portal hypertension while receiving TRIKAFTA. Avoid use of TRIKAFTA in patients with pre-existing advanced liver disease (e.g., as evidenced by cirrhosis, portal hypertension, ascites, hepatic encephalopathy) unless the benefits are expected to outweigh the risks. If used in these patients, they should be closely monitored after the initiation of treatment
- Isolated elevations of transaminases or bilirubin have been observed in patients with CF treated with TRIKAFTA. In some instances, transaminase elevations have been associated with concomitant elevations in total bilirubin and/or international normalized ratio (INR) and have resulted in patients being hospitalized for intervention, including in patients without a history of pre-existing liver disease
- Assessments of liver function tests (ALT, AST, and bilirubin) are recommended prior to initiating TRIKAFTA, every 3 months during the first year of treatment, and annually thereafter
- In the event of significant elevations in liver function tests, e.g. ALT or AST >5x the upper limit of normal (ULN) or ALT or AST >3x ULN with bilirubin >2x ULN, dosing should be interrupted and laboratory tests closely followed until the abnormalities resolve. Following the resolution of liver function test elevations, consider the benefits and risks of resuming treatment
- For patients with a history of hepatobiliary disease or liver function test elevations, more frequent monitoring should be considered
Indications and Usage
TRIKAFTA is indicated for the treatment of cystic fibrosis (CF) in patients aged 6 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 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 F508del mutation or a mutation that is responsive based on in vitro data.
Concomitant Use With CYP3A Inducers
- Exposure to ivacaftor is significantly decreased and exposure to elexacaftor and tezacaftor are expected to decrease by the concomitant use of strong CYP3A inducers, which may reduce the therapeutic effectiveness of TRIKAFTA. Co‑administration with strong CYP3A inducers is not recommended
Concomitant Use With CYP3A Inhibitors
- Exposure to elexacaftor, tezacaftor, and ivacaftor are increased when co-administered with strong or moderate CYP3A inhibitors. The dose of TRIKAFTA should be reduced when used concomitantly with moderate or strong CYP3A inhibitors
Cataracts
- Cases of 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
Pediatric Use
- The safety and effectiveness of TRIKAFTA in patients with CF younger than 6 years of age have not been established
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 (N=202) and higher than placebo (N=201) by ≥1% in the 24-week placebo-controlled, parallel-group Phase 3 trial (Trial 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, and blood bilirubin increased
- The safety profile for the patients with CF receiving TRIKAFTA (N=55) enrolled in the 4-week, randomized, double-blind, active-controlled Phase 3 trial (Trial 2) was similar to that observed in Trial 1
- The safety profile in patients age 6 to less than 12 years from an open-label Phase 3 trial (N=66) was similar to that observed in trials of patients age 12 years and older
Click here to access full Prescribing Information for TRIKAFTA.
References:
1. TRIKAFTA [prescribing information]. Boston, MA: Vertex Pharmaceuticals Incorporated; October 2021. 2. Data on file. Vertex Pharmaceuticals Incorporated. Boston, MA. REF-6607 (v2.0); 2021.