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DOSING AND ADMINISTRATION¹

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

	← ~12 hours apart →
	MORNING	EVENING
RECOMMENDED DOSAGE	elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg 2 tablets	ivacaftor 150 mg 1 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 A CLEAR MEDICAL NEED AND THE BENEFIT EXCEEDS THE RISK^a,b
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	IN THE MORNING (TWICE A WEEK) DAY 1 elexacaftor 100 mg/ tezacaftor 50 mg/ ivacaftor 75 mg 2 tablets DAY 4^c elexacaftor 100 mg/ tezacaftor 50 mg/ ivacaftor 75 mg 2 tablets	NO TABLET IN THE EVENING
Moderate CYP3A inhibitors including: fluconazole, erythromycin	ALTERNATE TABLETS EVERY MORNING DAY 1 elexacaftor 100 mg/ tezacaftor 50 mg/ ivacaftor 75 mg 2 tablets DAY 2^d ivacaftor 150 mg 1 tablet	NO TABLET IN THE EVENING

Tablets are not actual size.

^aLiver function tests should be closely monitored.¹
^bUse in patients with moderate hepatic impairment should only be considered when there is a clear medical need and the benefit exceeds the risk.¹
If TRIKAFTA is used, it should be with caution and at a reduced dose, as follows:

Day 1: take two elexacaftor/tezacaftor/ivacaftor tablets in the morning
Day 2: take one 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

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

← ~12 hours apart →
MORNING	EVENING

Recommended dosage
elexacaftor 100 mg/ tezacaftor 50 mg/ ivacaftor 75 mg 2 tablets	ivacaftor 150 mg 1 tablet

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 RISK^a,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
IN THE MORNING (TWICE A WEEK) DAY 1 elexacaftor 100 mg/ tezacaftor 50 mg/ ivacaftor 75 mg 2 tablets DAY 4^c elexacaftor 100 mg/ tezacaftor 50 mg/ ivacaftor 75 mg 2 tablets	NO TABLET IN THE EVENING

Moderate CYP3A inhibitors including: fluconazole, erythromycin
ALTERNATE TABLETS EVERY MORNING DAY 1 elexacaftor 100 mg/ tezacaftor 50 mg/ ivacaftor 75 mg 2 tablets DAY 2^d ivacaftor 150 mg 1 tablet	NO TABLET IN THE EVENING

Tablets are not actual size.

Day 1: take two elexacaftor/tezacaftor/ivacaftor tablets in the morning
Day 2: take one elexacaftor/tezacaftor/ivacaftor tablet in the morning
Continue alternating Day 1 and Day 2 dosing thereafter
No evening dose of ivacaftor should be taken

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
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.

	MISSED DOSE¹
	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
Morning and evening doses should not be taken at the same time.

TRIKAFTA is supplied in cartons containing 4 weekly wallets, each with 21 tablets
(NDC: 51167-331-01)¹

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

See potential drug-drug interactions >

View the clinical trials of TRIKAFTA >

Indications and Usage

TRIKAFTA is indicated for the treatment of cystic fibrosis (CF) in patients aged 12 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.

Important Safety Information

Liver Function Test Elevations

Elevated transaminases have been observed in patients with CF treated with TRIKAFTA. Bilirubin elevations have also been observed with TRIKAFTA treatment. 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. For patients with a history of hepatobiliary disease or liver function test elevations, more frequent monitoring should be considered

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

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 12 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). There were no deaths in Trials 1 and 2

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

Click here to access full Prescribing Information for TRIKAFTA.

Indications and Usage

Important Safety Information

Liver Function Test Elevations

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

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 12 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). There were no deaths in Trials 1 and 2

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

Click here to access full Prescribing Information for TRIKAFTA.

DOSING AND ADMINISTRATION1

Indications and Usage

Important Safety Information

Liver Function Test Elevations

Liver Function Test Elevations

Indications and Usage

Important Safety Information

Liver Function Test Elevations

Liver Function Test Elevations

DOSING AND ADMINISTRATION¹