Trikafta Elexacaftor, Tezacaftor, and Ivacaftor Kit

1 INDICATIONS AND USAGE TRIKAFTA is indicated for the treatment of cystic fibrosis (CF) in adult and pediatric patients aged 2 years and older who have a clinical diagnosis of CF and who have at least one variant in the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene that is either responsive based on clinical and/or in vitro data (see Table 6 ) or results in production of CFTR protein [see Clinical Pharmacology (12.1) ] . If the patient's genotype is unknown, an FDA-cleared CF genetic test should be used to confirm the presence of at least one variant in the CFTR gene that is either responsive based on clinical and/or in vitro data or results in production of CFTR protein.

TRIKAFTA is a combination of ivacaftor, a CFTR potentiator, tezacaftor, and elexacaftor indicated for the treatment of cystic fibrosis (CF) in adult and pediatric patients aged 2 years and older who have a clinical diagnosis of CF and who have at least one variant in the CFTR gene that is either responsive based on clinical and/or in vitro data or results in production of CFTR protein. ( 1 , 12.1 ) If the patient's genotype is unknown, an FDA-cleared CF genetic test should be used to confirm the presence of at least one variant in the CFTR gene that is either responsive based on clinical and/or in vitro data or results in production of CFTR protein.

( 1 )

2 DOSAGE AND ADMINISTRATION Prior to initiating TRIKAFTA obtain liver function tests (ALT, AST, alkaline phosphatase, and bilirubin) in all patients. Monitor liver function tests every month during the first 6 months of treatment, then every 3 months during the next 12 months, then at least annually thereafter. ( 2.1 , 5.1) Recommended Dosage for Adult and Pediatric Patients Aged 2 Years and Older (with fat-containing food ( 2.2 , 12.3 )) Age Weight Morning Dose Evening Dose 2 to less than 6 years Less than 14 kg One packet containing elexacaftor 80 mg/tezacaftor 40 mg/ivacaftor 60 mg oral granules One packet containing ivacaftor 59.5 mg oral granules 14 kg or more One packet containing elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg oral granules One packet containing ivacaftor 75 mg oral granules 6 to less than 12 years Less than 30 kg Two tablets, each containing elexacaftor 50 mg/tezacaftor 25 mg/ivacaftor 37.5 mg One tablet of ivacaftor 75 mg 30 kg or more Two tablets, each containing elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg One tablet of ivacaftor 150 mg 12 years and older - Two tablets, each containing elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg One tablet of ivacaftor 150 mg Should not be used in patients with severe hepatic impairment.

Use not recommended in patients with moderate hepatic impairment unless the benefit outweighs the risk. Reduce dose if used in patients with moderate hepatic impairment. Liver function tests should be closely monitored.

( 2.3 , 5.1 , 6 , 8.7 , 12.3 ) See full prescribing information for dosage modifications due to drug interactions with TRIKAFTA. ( 2.4 , 5.6 , 7.1 , 12.3 )

2.1Recommended Laboratory Testing Prior to TRIKAFTA Initiation and During Treatment Prior to initiating TRIKAFTA, obtain liver function tests (ALT, AST, alkaline phosphatase, and bilirubin) for all patients. Monitor liver function tests every month during the first 6 months of treatment, then every 3 months for the next 12 months, then at least annually thereafter. Consider more frequent monitoring for patients with a history of liver disease or liver function test elevations at baseline [see Warnings and Precautions (5.1) and Use in Specific Populations (8.7) ] .

2.2Recommended Dosage in Adults and Pediatric Patients Aged 2 Years and Older Recommended dosage for adult and pediatric patients aged 2 years and older is provided in Table 1. Administer TRIKAFTA tablets (swallow the tablets whole) or oral granules orally with fat-containing food, in the morning and in the evening approximately 12 hours apart. Examples of meals or snacks that contain fat are those prepared with butter or oils or those containing eggs, peanut butter, cheeses, nuts, whole milk, or meats [see Clinical Pharmacology (12.3) ] .

Administer each dose of TRIKAFTA oral granules immediately before or after ingestion of fat-containing food. Mix entire contents of each packet of oral granules with one teaspoon (5 mL) of age-appropriate soft food or liquid that is at or below room temperature. Some examples of soft food or liquids include pureed fruits or vegetables, yogurt, applesauce, water, milk, or juice.

Once mixed, the product should be consumed completely within one hour. Table 1: Recommended Dosage of TRIKAFTA for Adult and Pediatric Patients Aged 2 Years and Older Age Weight Oral Morning Dose Oral Evening Dose 2 to less than 6 years Less than 14 kg One packet (containing elexacaftor 80 mg/tezacaftor 40 mg/ivacaftor 60 mg) oral granules One packet (containing ivacaftor 59.5 mg) oral granules 14 kg or more One packet (containing elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg) oral granules One packet (containing ivacaftor 75 mg) oral granules 6 to less than 12 years Less than 30 kg Two tablets of elexacaftor 50 mg/tezacaftor 25 mg/ivacaftor 37.5 mg (total dose of elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg) One tablet of ivacaftor 75 mg 30 kg or more Two tablets of elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor…

3 DOSAGE FORMS AND STRENGTHS Tablets: Fixed-dose combination containing elexacaftor 50 mg, tezacaftor 25 mg and ivacaftor 37.5 mg co-packaged with ivacaftor 75 mg; Fixed-dose combination containing elexacaftor 100 mg, tezacaftor 50 mg, and ivacaftor 75 mg co-packaged with ivacaftor 150 mg. ( 3 ) Oral granules: Unit-dose packets of elexacaftor 100 mg, tezacaftor 50 mg and ivacaftor 75 mg co-packaged with unit-dose packets of ivacaftor 75 mg; Unit-dose packets of elexacaftor 80 mg, tezacaftor 40 mg and ivacaftor 60 mg co-packaged with unit-dose packets of ivacaftor 59.5 mg.

( 3 ) Tablets : Fixed-dose combination containing elexacaftor 50 mg, tezacaftor 25 mg, and ivacaftor 37.5 mg co-packaged with ivacaftor 75 mg: Elexacaftor, tezacaftor and ivacaftor tablets are light orange, oblong-shaped and debossed with "T50" on one side and plain on the other Ivacaftor tablets are light blue, oblong-shaped, and printed with "V 75" in black ink on one side and plain on the other Fixed-dose combination containing elexacaftor 100 mg, tezacaftor 50 mg, and ivacaftor 75 mg co-packaged with 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, oblong-shaped, and printed with "V 150" in black ink on one side and plain on the other Oral Granules : Fixed-dose combination oral granules containing elexacaftor 100 mg, tezacaftor 50 mg, and ivacaftor 75 mg co-packaged with ivacaftor 75 mg oral granules: Elexacaftor, tezacaftor, and ivacaftor oral granules are white to off-white, sweetened, unflavored granules approximately 2 mm in diameter contained in a white and orange unit-dose packet Ivacaftor oral granules are white to off-white, sweetened, unflavored granules approximately 2 mm in diameter contained in a white and pink unit-dose packet Fixed-dose combination oral granules containing elexacaftor 80 mg, tezacaftor 40 mg, and ivacaftor 60 mg co-packaged with ivacaftor 59.5 mg oral granules: Elexacaftor, tezacaftor, and ivacaftor oral granules are white to off-white, sweetened, unflavored granules approximately 2 mm in diameter contained in a white and blue unit-dose packet Ivacaftor oral granules are white to off-white, sweetened, unflavored granules approximately 2 mm in diameter contained in a white and green unit-dose packet

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Drug-Induced Liver Injury and Liver Failure Inform patients that TRIKAFTA is associated with a serious risk for drug-induced liver injury and that liver injury resulting in liver failure leading to liver transplantation or death have occurred, including in patients without a history of liver disease. Advise all patients that liver function tests (ALT, AST, alkaline phosphatase, and bilirubin) should be assessed prior to initiating TRIKAFTA and then assessed every month during the first 6 months of treatment, then every 3 months for the next 12 months, then at least annually thereafter.

Inform patients with a history of liver disease or liver function test elevations at baseline that more frequent monitoring may be necessary. Instruct patients to interrupt treatment with TRIKAFTA if symptoms of liver injury occur (e.g., jaundice, right upper quadrant pain, nausea, vomiting, altered mental status, ascites) and to notify their healthcare provider immediately. [see Dosage and Administration (2.1) and Warnings and Precautions (5.1) ] . Drug Interactions with CYP3A Inducers and Inhibitors Ask patients to tell you all the medications they are taking including any herbal supplements or vitamins.

Inform patients that concomitant use of TRIKAFTA with strong CYP3A inducers (e.g., rifampin, St. John's wort) is not recommended, as they may reduce the efficacy of TRIKAFTA. Dose reduction to two elexacaftor/tezacaftor/ivacaftor tablets or one elexacaftor/tezacaftor/ivacaftor oral granules packet twice a week, taken approximately 3 to 4 days apart is recommended when used concomitantly with strong CYP3A inhibitors, such as ketoconazole.

Advise the patient not to take the evening dose of ivacaftor. Dose reduction to two elexacaftor/tezacaftor/ivacaftor tablets or one elexacaftor/tezacaftor/ivacaftor oral granules packet and one ivacaftor tablet or ivacaftor oral granules packet, taken on alternate days, is recommended when used concomitantly with moderate CYP3A inhibitors, such as fluconazole. Advise the patient not to take the evening dose of ivacaftor.

Food or drink containing grapefruit should be avoided [see Dosage and Administration (2.4) , Warnings and Precautions (5.5 , 5.6 ), Drug Interactions (7.1) and Clinical Pharmacology (12.3) ] . Hypersensitivity Reactions, Including Anaphylaxis Hypersensitivity reactions including angioedema and anaphylaxis are possible with use of TRIKAFTA. Inform patients of the early signs of hypersensitivity reactions including rash, hives, itching, facial swelling, tightness of the chest and wheezing.

Advise patients to discontinue use of TRIKAFTA immediately and contact their physician or go to the emergency department if these symptoms occur [see Warnings and Precautions (5.2) ] . Intracranial Hypertension Inform patients that intracranial hypertension has occurred with the use of TRIKAFTA. Instruct patients to notify their healthcare provider right away if they experience signs and symptoms of intracranial hypertension, including headache, blurred vision, diplopia, and vision loss [see Warnings and Precautions (5.3) ] .

Neuropsychiatric Events, Including Suicidal Thoughts and Behaviors Inform patients that neuropsychiatric symptoms, including anxiety, depression, suicidal thoughts and behaviors, and sleep disturbances (e.g., insomnia), have been reported with the use of TRIKAFTA or drugs containing the same or similar active ingredients as TRIKAFTA. The symptoms have been observed in patients with and without a history of similar symptoms and may occur within three months of TRIKAFTA initiation. Instruct patients to contact their healthcare provider immediately if changes in behavior or thinking that are not typical for the patient occur, or if the patient develops suicidal ideation or behavior [see Warnings and Precautions (5.4) ] .

Cataracts Inform patients that abnormality of the eye lens…

This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: 03/2026 MEDICATION GUIDE TRIKAFTA ® (tri-KAF-tuh) (elexacaftor, tezacaftor, and ivacaftor tablets; ivacaftor tablets), co-packaged for oral use (elexacaftor, tezacaftor, and ivacaftor oral granules; ivacaftor oral granules), co-packaged What is the most important information I should know about TRIKAFTA?

TRIKAFTA can cause serious liver damage and liver failure. Liver failure leading to transplantation and death have been seen in some people with or without a history of liver problems taking TRIKAFTA. Your healthcare provider will do blood tests to check your liver: before you start TRIKAFTA then every month during your first 6 months of taking TRIKAFTA then every 3 months during the next 12 months of taking TRIKAFTA then at least every year while you are taking TRIKAFTA Your healthcare provider may do blood tests to check the liver more often if you have had high liver enzymes in your blood in the past or are experiencing signs or symptoms of liver injury.

Stop taking TRIKAFTA and call your healthcare provider right away if you have any of the following symptoms of liver problems: pain, swelling, or discomfort in the upper right stomach (abdominal) area yellowing of your skin or the white part of your eyes mental changes nausea or vomiting dark, amber-colored urine loss of appetite have fluid in your stomach area (ascites) What is TRIKAFTA? TRIKAFTA is a prescription medicine for people aged 2 years and older who have a diagnosis of cystic fibrosis (CF) and who have at least one genetic change (variant) in the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene that is either responsive to TRIKAFTA or results in the production of protein.

Talk to your healthcare provider to learn if you have an indicated CF gene variant. It is not known if TRIKAFTA is safe and effective in children under 2 years of age. What should I tell my healthcare provider before taking TRIKAFTA?

Before taking TRIKAFTA, tell your healthcare provider about all of your medical conditions, including if you: have or have had liver problems. are allergic to TRIKAFTA or any ingredients in TRIKAFTA. See the end of this Medication Guide for a complete list of ingredients in TRIKAFTA. have kidney problems. have or have had mental health problems. are pregnant or plan to become pregnant. It is not known if TRIKAFTA will harm your unborn baby.

You and your healthcare provider should decide if you will take TRIKAFTA while you are pregnant. are breastfeeding or planning to breastfeed. It is not known if TRIKAFTA passes into your breast milk. You and your healthcare provider should decide if you will take TRIKAFTA while you are breastfeeding.

Tell your healthcare provider about all the medicines you take , including prescription and over-the-counter medicines, vitamins, and herbal supplements. TRIKAFTA may affect the way other medicines work and other medicines may affect how TRIKAFTA works. The dose of TRIKAFTA may need to be adjusted when taken with certain medicines.

Ask your healthcare provider or pharmacist for a list of these medicines if you are not sure. Especially tell your healthcare provider if you take: antibiotics such as rifampin (RIFAMATE, RIFATER) or rifabutin (MYCOBUTIN). seizure medicines such as phenobarbital, carbamazepine (TEGRETOL, CARBATROL, EQUETRO), or phenytoin (DILANTIN, PHENYTEK). St.

John's wort antifungal medicines including ketoconazole, itraconazole (such as SPORANOX), posaconazole (such as NOXAFIL), voriconazole (such as VFEND), or fluconazole (such as DIFLUCAN). antibiotics including telithromycin, clarithromycin (such as BIAXIN), or erythromycin (such as ERY-TAB). Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

How should I take TRIKAFTA? Take TRIKAFTA exactly as your healthcare provider tells you to take it. Take TRIKAFTA by mouth only.

TRIKAFTA consist…