Version July 2025
Elexacaftor/tezacaftor/ivacaftor 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 elexacaftor/tezacaftor/ivacaftor, 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 elexacaftor/tezacaftor/ivacaftor.
Assess liver function tests (ALT, AST, alkaline phosphatase, and bilirubin) in all patients prior to initiating elexacaftor/tezacaftor/ivacaftor. Assess 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.
Interrupt elexacaftor/tezacaftor/ivacaftor for significant elevations in liver function tests 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 abnormalities resolve, resume treatment only if benefit is expected to outweigh the risk. Closer monitoring is advised after resuming elexacaftor/tezacaftor/ivacaftor.
Elexacaftor/tezacaftor/ivacaftor should not be used in patients with severe hepatic impairment (Child-Turcotte-Pugh class C). Elexacaftor/tezacaftor/ivacaftor is not recommended in patients with moderate hepatic impairment (Child-Turcotte-Pugh class B). If used, use with caution at a reduced dosage and monitor patients closely.
Dosage guidance:
Dosage form information: Trikafta is supplied as 2 separate products packaged together: Elexacaftor/tezacaftor/ivacaftor (orange capsule-shaped tablets) in a fixed-dose combination and ivacaftor (blue capsule-shaped tablets).
Cystic fibrosis: Oral: 2 tablets (each containing elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg per tablet) in the morning and one ivacaftor 150 mg tablet in the evening, approximately 12 hours apart.
Missed dose:
Morning dose: If ≤6 hours since the missed morning dose, take the missed dose as soon as possible and continue the original schedule. If >6 hours since the missed morning dose, take the missed dose as soon as possible and do not take the evening dose. The next scheduled morning dose should be taken at the usual time.
Evening dose: If ≤6 hours since the missed evening dose, take the missed dose as soon as possible and continue the original schedule. If >6 hours since the missed evening dose, do not take the missed dose. The next scheduled morning dose should be taken at the usual time.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information
eGFR ≥30 mL/minute/1.73 m2: No dosage adjustment necessary.
eGFR <30 mL/minute/1.73 m2: There are no specific dosage adjustments provided in the manufacturer's labeling (has not been studied); use with caution.
End-stage renal disease: There are no specific dosage adjustments provided in the manufacturer's labeling (has not been studied); use with caution.
Hepatic impairment prior to treatment initiation:
Mild impairment (Child-Turcotte-Pugh class A): No dosage adjustment necessary; monitor LFTs closely.
Moderate impairment (Child-Turcotte-Pugh class B): Use not recommended; however, if there is a medical need and benefits outweigh risks, use with caution and close monitoring of LFTs.
Day 1: Reduce dose to 2 tablets (each containing elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg per tablet) in the morning (omit the evening ivacaftor dose).
Day 2: Reduce dose to 1 tablet (each containing elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg per tablet) in the morning (omit the evening ivacaftor dose).
Day 3 and thereafter: Alternate between day 1 and day 2 dosing.
Severe impairment (Child-Turcotte-Pugh class C): Use not recommended (has not been studied); exposure is expected to be higher than in patients with moderate impairment.
Hepatotoxicity during treatment: ALT/AST >5 × ULN or ALT/AST >3 × ULN with bilirubin >2 × ULN and/or symptoms suggestive of liver injury (eg, ascites, jaundice, nausea, altered mental status, right upper quadrant pain, vomiting): Interrupt therapy and monitor closely until resolved; consider referral to hepatologist. Consider the benefits and risks prior to resuming treatment and monitor closely.
Has not been studied.
(For additional information see "Elexacaftor, tezacaftor, and ivacaftor co-packaged with ivacaftor: Pediatric drug information")
Dosage guidance:
Dosage form information: Trikafta is supplied as 2 separate products packaged together: Elexacaftor/tezacaftor/ivacaftor in a fixed-dose combination copackaged with ivacaftor; use caution when selecting dosage form; multiple strengths are available; appropriate strength is dependent on patient age and weight.
Cystic fibrosis (CF):
Children 2 to <6 years: Oral granules:
Weight <14 kg: Elexacaftor 80 mg/tezacaftor 40 mg/ivacaftor 60 mg per packet and ivacaftor 59.5 mg per packet:
Oral: 1 packet (total dose of elexacaftor 80 mg/tezacaftor 40 mg/ivacaftor 60 mg) in the morning and one ivacaftor 59.5 mg packet in the evening approximately 12 hours apart.
Weight ≥14 kg: Elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg per packet and ivacaftor 75 mg packet:
Oral: 1 packet (total dose of elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg) in the morning and one ivacaftor 75 mg packet in the evening approximately 12 hours apart.
Children 6 to <12 years: Oral tablets:
Weight <30 kg: Elexacaftor 50 mg/tezacaftor 25 mg/ivacaftor 37.5 mg per tablet and ivacaftor 75 mg per tablet:
Oral: 2 tablets (total dose of elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg) in the morning and one ivacaftor 75 mg tablet in the evening, approximately 12 hours apart.
Weight ≥30 kg: Elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg per tablet and ivacaftor 150 mg per tablet:
Oral: 2 tablets (total dose of elexacaftor 200 mg/tezacaftor 100 mg/ivacaftor 150 mg) in the morning and one ivacaftor 150 mg tablet in the evening, approximately 12 hours apart.
Children ≥12 years and Adolescents: Elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg per tablet and ivacaftor 150 mg per tablet:
Oral: 2 tablets (total dose of elexacaftor 200 mg/tezacaftor 100 mg/ivacaftor 150 mg) in the morning and one ivacaftor 150 mg tablet in the evening, approximately 12 hours apart.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Altered kidney function: Children ≥2 years and Adolescents: Oral:
eGFR >30 mL/minute/1.73 m2: No dosage adjustment necessary.
eGFR ≤30 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling; use with caution; has not been studied.
End-stage renal disease: There are no dosage adjustments provided in the manufacturer's labeling; use with caution; has not been studied.
Note: Use caution when selecting dosage form; multiple strengths are available.
Hepatic impairment prior to initiation (baseline):
Mild impairment: Children ≥2 years and Adolescents: Oral: No dosage adjustment necessary; monitor LFTs closely.
Moderate impairment: Note: Use is not recommended; may consider use only if medical need is clear and benefit outweighs risk. If used, monitor liver function closely and reduce dose as follows:
Children 2 to <6 years:
Weight <14 kg: Elexacaftor 80 mg/tezacaftor 40 mg/ivacaftor 60 mg per packet and ivacaftor 59.5 mg per packet:
Days 1 to 3: Oral: 1 packet (total dose elexacaftor 80 mg/tezacaftor 40 mg/ivacaftor 60 mg) once in the morning; omit the evening dose of ivacaftor.
Day 4: No dose.
Days 5 and 6: Oral: 1 packet (total dose of elexacaftor 80 mg/tezacaftor 40 mg/ivacaftor 60 mg) once in the morning; omit the evening dose of ivacaftor.
Day 7: No dose.
Repeat same cycle weekly.
Weight ≥14 kg: Elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg per packet and ivacaftor 75 mg per packet:
Days 1 to 3: Oral: 1 packet (total dose of elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg) once in the morning; omit the evening dose of ivacaftor.
Day 4: No dose.
Days 5 and 6: Oral: 1 packet (total dose of elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg) once in the morning; omit the evening dose of ivacaftor.
Day 7: No dose.
Repeat same cycle weekly.
Children 6 to <12 years:
Weight <30 kg: Elexacaftor 50 mg/tezacaftor 25 mg/ivacaftor 37.5 mg per tablet and ivacaftor 75 mg per tablet:
Day 1: Oral: 2 tablets (total dose of elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg) once in the morning; omit the evening dose of ivacaftor.
Day 2: Oral: 1 tablet (total dose of elexacaftor 50 mg/tezacaftor 25 mg/ivacaftor 37.5 mg) once in the morning; omit the evening dose of ivacaftor.
Day 3 and subsequent days: Continue alternating Day 1 and Day 2 regimens thereafter.
Weight ≥30 kg: Elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg per tablet and ivacaftor 150 mg per tablet:
Day 1: Oral: 2 tablets (total dose of elexacaftor 200 mg/tezacaftor 100 mg/ivacaftor 150 mg) once in the morning; omit the evening dose of ivacaftor.
Day 2: Oral: 1 tablet (total dose of elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg) once in the morning; omit the evening dose of ivacaftor.
Day 3 and subsequent days: Continue alternating Day 1 and Day 2 regimens thereafter.
Children ≥12 years and Adolescents: Elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg per tablet and ivacaftor 150 mg per tablet:
Day 1: Oral: 2 tablets (total dose of elexacaftor 200 mg/tezacaftor 100 mg/ivacaftor 150 mg) once in the morning; omit the evening dose of ivacaftor.
Day 2: Oral: 1 tablet (total dose of elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg) once in the morning; omit the evening dose of ivacaftor.
Day 3 and subsequent days: Continue alternating Day 1 and Day 2 regimens thereafter.
Severe impairment: Children ≥2 years and Adolescents: Oral: Use not recommended (has not been studied); exposure is higher in patients with moderate liver impairment.
Hepatotoxicity during treatment: Children ≥2 years and Adolescents: Oral:
ALT or AST >5 × ULN: Temporarily discontinue elexacaftor/tezacaftor/ivacaftor; consider hepatologist referral. May resume if laboratory abnormalities are resolved and benefit is expected to outweigh risk; monitor closely.
ALT or AST >3 × ULN with concomitant bilirubin >2 × ULN: Temporarily discontinue elexacaftor/tezacaftor/ivacaftor; consider hepatologist referral. May resume if laboratory abnormalities are resolved and benefit is expected to outweigh risk; monitor closely.
Clinical signs or symptoms suggestive of liver injury (eg, jaundice, right upper quadrant pain, nausea, vomiting, altered mental status, ascites): Temporarily discontinue elexacaftor/tezacaftor/ivacaftor; consider hepatologist referral. May resume if signs or symptoms are resolved and benefit is expected to outweigh risk; monitor closely.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adolescents and adults unless otherwise indicated. Also see Tezacaftor and Ivacaftor, and Ivacaftor.
>10%:
Dermatologic: Skin rash (children, adolescents, adults: 10% to 23%; incidence higher in females)
Gastrointestinal: Abdominal pain (14%), diarrhea (children, adolescents, adults: 13%)
Hepatic: Increased indirect serum bilirubin (11%), increased serum transaminases (11%; including increased serum alanine aminotransferase [10%], increased serum aspartate aminotransferase [9%])
Nervous system: Headache (children, adolescents, adults: 17% to 18%)
Respiratory: Upper respiratory tract infection (16%)
1% to 10%:
Cardiovascular: Increased systolic blood pressure (4%)
Dermatologic: Acne vulgaris (2% to 5%), eczema (2% to 5%), pruritus (2% to 5%)
Endocrine & metabolic: Hypoglycemia (2% to 5%)
Gastrointestinal: Abdominal distention (2% to 5%), constipation (children, adolescents, adults: 7%), flatulence (2% to 5%)
Genitourinary: Dysmenorrhea (2% to 5%), urinary tract infection (2% to 5%)
Hematologic & oncologic: C-reactive protein increased (2% to 5%)
Hepatic: Increased direct serum bilirubin (3%), increased serum bilirubin (5%)
Infection: Influenza (children, adolescents, adults: 7% to 9%)
Nervous system: Dizziness (2% to 5%)
Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen (9%)
Ophthalmic: Conjunctivitis (2% to 5%)
Respiratory: Nasal congestion (9%), pharyngitis (2% to 5%), respiratory tract infection (2% to 5%), rhinitis (children, adolescents, adults: 7% to 10%), rhinorrhea (8%), sinusitis (5%), tonsillitis (2% to 5%)
Postmarketing:
Gastrointestinal: Vomiting (Wainwright 2023)
Hepatic: Hepatic failure, hepatic injury
Hypersensitivity: Hypersensitivity reaction (including anaphylaxis, angioedema)
Nervous system: Intracranial hypertension (idiopathic) (Wainwright 2023)
Respiratory: Cough (Wainwright 2023)
Miscellaneous: Fever (Wainwright 2023)
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to elexacaftor, tezacaftor, ivacaftor, or any component of the formulation.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Concerns related to adverse effects:
• Cataracts: Noncongenital lens opacities and cataracts have been reported in pediatric patients treated with ivacaftor; other risk factors were present in some cases (eg, corticosteroid use, exposure to radiation), but a possible risk related to ivacaftor cannot be excluded. Baseline and follow-up ophthalmological examinations are recommended in pediatric patients.
• Hypersensitivity reactions: Hypersensitivity reactions, including anaphylaxis, have been reported with elexacaftor/tezacaftor/ivacaftor use. If signs and symptoms of severe hypersensitivity occur, discontinue use and treat appropriately; consider risk versus benefit prior to resuming therapy.
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with hepatic impairment; dosage adjustment recommended in patients with moderate impairment (Child-Pugh class B); use not recommended in severe impairment (Child-Pugh class C).
• Renal impairment: Use with caution in patients with severe renal impairment (eGFR <30 mL/minute/1.73 m2) or end-stage renal disease.
Other warnings/precautions:
• Appropriate use: If the patient's genotype is unknown, use an FDA-cleared cystic fibrosis mutation test to detect the presence of at least one F508del mutation.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet Therapy Pack, Oral:
Trikafta: Elexacaftor 100 mg, ivacaftor 75 mg, and tezacaftor 50 mg (56 ea) plus ivacaftor 150 mg (28 ea) (84 ea); Elexacaftor 50 mg, ivacaftor 37.5 mg, and tezacaftor 25 mg (56 ea) plus ivacaftor 75 mg (28 ea) (84 ea) [contains fd&c blue #2 (indigotine,indigo carmine)]
Therapy Pack, Oral:
Trikafta: Elexacaftor 100 mg, ivacaftor 75 mg, and tezacaftor 50 mg (7 ea) plus ivacaftor 75 mg (7 ea) (14 ea); Elexacaftor 80 mg, ivacaftor 60 mg, and tezacaftor 40 mg (7 ea) plus ivacaftor 59.5 mg (7 ea) (14 ea) [unflavored flavor]
No
Tablet Therapy Pack (Trikafta Oral)
50-25-37.5 & 75 mg (per each): $379.23
100-50-75 & 150 mg (per each): $379.23
Therapy Pack (Trikafta Oral)
80-40-60 & 59.5 mg (per each): $568.84
100-50-75 & 75 mg (per each): $568.84
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet Therapy Pack, Oral:
Trikafta: Elexacaftor 100 mg, ivacaftor 75 mg, and tezacaftor 50 mg (56 ea) plus ivacaftor 150 mg (28 ea) (84 ea); Elexacaftor 50 mg, ivacaftor 37.5 mg, and tezacaftor 25 mg (56 ea) plus ivacaftor 75 mg (28 ea) (84 ea) [contains fd&c blue #2 (indigo carm) aluminum lake]
Therapy Pack, Oral:
Trikafta: Elexacaftor 100 mg, ivacaftor 75 mg, and tezacaftor 50 mg (7 ea) plus ivacaftor 75 mg (7 ea) (56 ea); Elexacaftor 80 mg, ivacaftor 60 mg, and tezacaftor 40 mg (7 ea) plus ivacaftor 59.5 mg (7 ea) (56 ea)
Product is only available via authorized pharmacies and distributors. Further information is available at https://www.vrtx.com/authorized-distributors.
Oral: Swallow tablets whole. Administer with a fat-containing meal or snack (eg, those prepared with butter or oils or those containing eggs, cheeses, nuts, peanut butter, whole milk, or meats).
Oral: Administer with fat-containing food (eg, eggs, butter, oils, cheese, nuts, peanut butter, meats, whole-milk dairy products). Avoid food or drink containing grapefruit.
Tablets: Swallow tablet whole.
Oral granules: Mix entire contents of each packet with 5 mL of age-appropriate soft food (eg, applesauce, pureed fruit or vegetables, yogurt) or liquid (eg, water, milk, juice) that is at or below room temperature. Once mixed, consume within 1 hour.
Missed dose:
Morning dose: If ≤6 hours since the missed morning dose, take the missed dose as soon as possible and continue the original schedule. If >6 hours since the missed morning dose, take the missed dose as soon as possible and do not take the evening dose. The next scheduled morning dose should be taken at the usual time.
Evening dose: If ≤6 hours since the missed evening dose, take the missed dose as soon as possible and continue the original schedule. If >6 hours since the missed evening dose, do not take the missed dose. The next scheduled morning dose should be taken at the usual time.
Cystic fibrosis: Treatment of cystic fibrosis in patients ≥2 years of age 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.
Substrate of BCRP, CYP3A4 (Major), OATP1B1/1B3, P-glycoprotein (Minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits P-glycoprotein;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Afatinib. Management: If combined, administer the P-gp inhibitor simultaneously with, or after, the dose of afatinib. Monitor closely for signs and symptoms of afatinib toxicity and if the combination is not tolerated, reduce the afatinib dose by 10 mg. Risk D: Consider Therapy Modification
Aliskiren: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Aliskiren. Risk C: Monitor
Beta-Acetyldigoxin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Beta-Acetyldigoxin. Risk C: Monitor
Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Bilastine. Risk X: Avoid
Celiprolol: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Celiprolol. Risk C: Monitor
Clofazimine: May increase serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Risk C: Monitor
Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: This combination is often contraindicated, but combined use may be permitted with dose adjustment and monitoring. Recommendations vary based on brand, indication, use of CYP3A4 inhibitors, and hepatic/renal function. See interaction monograph for details. Risk D: Consider Therapy Modification
CycloSPORINE (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of CycloSPORINE (Systemic). Risk C: Monitor
CYP3A4 Inducers (Moderate): May decrease serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Risk C: Monitor
CYP3A4 Inducers (Strong): May decrease serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Risk X: Avoid
CYP3A4 Inhibitors (Moderate): May increase serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Management: When combined with moderate CYP3A4 inhibitors, elexacaftor/tezacaftor/ivacaftor should be given in the morning, every other day. Ivacaftor alone should be given in the morning, every other day on alternate days. Risk D: Consider Therapy Modification
CYP3A4 Inhibitors (Strong): May increase serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Management: Administer elexacaftor/tezacaftor/ivacaftor in the morning, twice a week, 3 to 4 days apart, with no evening doses of ivacaftor alone. Specific dosing varies by age and weight. See full monograph for details. Risk D: Consider Therapy Modification
Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase active metabolite exposure of Dabigatran Etexilate. Risk C: Monitor
Digitoxin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Digitoxin. Risk C: Monitor
Digoxin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Digoxin. Management: Measure digoxin serum concentrations before initiating treatment with these P-glycoprotein (P-gp) inhibitors. Reduce digoxin concentrations by either reducing the digoxin dose by 15% to 30% or by modifying the dosing frequency. Risk D: Consider Therapy Modification
DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of DOXOrubicin (Conventional). Risk X: Avoid
DOXOrubicin (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of DOXOrubicin (Liposomal). Risk C: Monitor
Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Edoxaban. Risk C: Monitor
Ensartinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Ensartinib. Risk X: Avoid
Etoposide Phosphate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Etoposide Phosphate. Risk C: Monitor
Etoposide: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Etoposide. Risk C: Monitor
Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Everolimus. Risk C: Monitor
Fusidic Acid (Systemic): May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider Therapy Modification
Glecaprevir and Pibrentasvir: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor
Glimepiride: Elexacaftor, Tezacaftor, and Ivacaftor may increase serum concentration of Glimepiride. Risk C: Monitor
GlipiZIDE: Elexacaftor, Tezacaftor, and Ivacaftor may increase serum concentration of GlipiZIDE. Risk C: Monitor
GlyBURIDE: Elexacaftor, Tezacaftor, and Ivacaftor may increase serum concentration of GlyBURIDE. Risk C: Monitor
Grapefruit Juice: May increase serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Specifically, the serum concentration of ivacaftor may be increased. Risk X: Avoid
HMG-CoA Reductase Inhibitors (Statins): Elexacaftor, Tezacaftor, and Ivacaftor may increase serum concentration of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor
Hormonal Contraceptives: May increase adverse/toxic effects of Elexacaftor, Tezacaftor, and Ivacaftor. Specifically, the risk for rash may be increased. Risk C: Monitor
Lapatinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Lapatinib. Risk C: Monitor
Larotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Larotrectinib. Risk C: Monitor
Lefamulin: Elexacaftor, Tezacaftor, and Ivacaftor may increase serum concentration of Lefamulin. Lefamulin may increase serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Management: Consider alternatives to this combination when possible. If combined, monitor for increased lefamulin toxicities and decrease the elexacaftor/tezacaftor/ivacaftor dose. See full monograph for details. Risk D: Consider Therapy Modification
Mavorixafor: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Mavorixafor. Risk C: Monitor
Morphine (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Morphine (Systemic). Risk C: Monitor
Nadolol: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Nadolol. Risk C: Monitor
Naldemedine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Naldemedine. Risk C: Monitor
Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Naloxegol. Risk C: Monitor
Nateglinide: Elexacaftor, Tezacaftor, and Ivacaftor may increase serum concentration of Nateglinide. Risk C: Monitor
PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of PAZOPanib. Risk X: Avoid
Phenobarbital-Primidone: May decrease serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Risk C: Monitor
Pralsetinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Pralsetinib. Management: If this combo cannot be avoided, decrease pralsetinib dose from 400 mg daily to 300 mg daily; from 300 mg daily to 200 mg daily; and from 200 mg daily to 100 mg daily. Risk D: Consider Therapy Modification
Ranolazine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Ranolazine. Risk C: Monitor
Relugolix, Estradiol, and Norethindrone: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Relugolix, Estradiol, and Norethindrone. Management: Avoid use of relugolix/estradiol/norethindrone with P-glycoprotein (P-gp) inhibitors. If concomitant use is unavoidable, relugolix/estradiol/norethindrone should be administered at least 6 hours before the P-gp inhibitor. Risk D: Consider Therapy Modification
Relugolix: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Relugolix. Management: Avoid coadministration of relugolix with oral P-gp inhibitors whenever possible. If combined, take relugolix at least 6 hours prior to the P-gp inhibitor and monitor patients more frequently for adverse reactions. Risk D: Consider Therapy Modification
Repaglinide: Elexacaftor, Tezacaftor, and Ivacaftor may increase serum concentration of Repaglinide. Risk C: Monitor
Repotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Repotrectinib. Risk X: Avoid
Rifabutin: May decrease serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Specifically, the serum concentration of ivacaftor may be decreased. Risk C: Monitor
RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of RifAXIMin. Risk C: Monitor
Rimegepant: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Rimegepant. Management: Avoid administration of another dose of rimegepant within 48 hours if given concomitantly with a P-glycoprotein (P-gp) inhibitor. Risk D: Consider Therapy Modification
RisperiDONE: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of RisperiDONE. Risk C: Monitor
RomiDEPsin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of RomiDEPsin. Risk C: Monitor
Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Silodosin. Risk C: Monitor
Sirolimus (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Sirolimus (Conventional). Management: Avoid concurrent use of sirolimus with P-glycoprotein (P-gp) inhibitors when possible and alternative agents with lesser interaction potential with sirolimus should be considered. Monitor for increased sirolimus concentrations/toxicity if combined. Risk D: Consider Therapy Modification
Sirolimus (Protein Bound): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Sirolimus (Protein Bound). Risk X: Avoid
St John's Wort: May decrease serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Specifically, the serum concentration of ivacaftor may be decreased. Risk X: Avoid
Tacrolimus (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Tacrolimus (Systemic). Risk C: Monitor
Talazoparib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Talazoparib. Risk C: Monitor
Teniposide: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Teniposide. Risk C: Monitor
Tenofovir Disoproxil Fumarate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor
Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Topotecan. Risk X: Avoid
Ubrogepant: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 50 mg and second dose (at least 2 hours later if needed) of 50 mg when used with a P-gp inhibitor. Risk D: Consider Therapy Modification
Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring concomitant treatment with P-glycoprotein (P-gp) inhibitors. Resume the previous venetoclax dose 2 to 3 days after discontinuation of a P-gp inhibitor. Risk D: Consider Therapy Modification
VinCRIStine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of VinCRIStine. Risk X: Avoid
Warfarin: Elexacaftor, Tezacaftor, and Ivacaftor may increase serum concentration of Warfarin. Risk C: Monitor
Grapefruit juice may increase exposure of elexacaftor, tezacaftor, or ivacaftor. Management: Avoid food or drink containing grapefruit during treatment.
Fertility and contraception should be reassessed prior to starting variant specific cystic fibrosis transmembrane conductance regulator (CFTR) therapy (Southern 2023). Fertility may improve with use of CFTR therapy and an increase in unintentional pregnancies has been observed. Contraception advice is recommended for patients who do not wish to become pregnant (Gramegna 2024; Southern 2023).
Elexacaftor, tezacaftor, and ivacaftor cross the placenta. Cord blood concentrations may be similar or higher than maternal serum concentrations (Collins 2022).
Data related to the safety of variant specific cystic fibrosis transmembrane conductance regulator (CFTR) therapy during pregnancy are limited (Southern 2023). Data following maternal use of this combination are available from case reports and case series (Balmpouzis 2022; Chamagne 2023; Cimino 2024; Kendle 2021; Kowalik 2024; Nuytten 2022; Szentpetery 2022; Taylor-Cousar 2021).
Monitoring of newborns exposed to CFTR therapy during pregnancy should include genetic testing, LFTs, and ophthalmic exams (Gramegna 2024). In addition, exposed infants may have a false negative immunoreactive trypsinogen test for cystic fibrosis during the newborn baby screen (Castellani 2023; Southern 2023).
Due to pregnancy-induced physiologic changes, some pharmacokinetic properties of CFTR therapy may be altered (Qiu 2020). Data specific to this combination are limited and show high interpatient variability (Christina 2025; Collins 2022). Dose adjustments based on routine clinical monitoring and therapeutic drug monitoring may be needed (Christina 2025). Increased monitoring during pregnancy is recommended (Gramegna 2024).
Patients taking variant specific CFTR therapy prior to pregnancy may have an acute deterioration of health if treatment is discontinued once pregnant. Continuing or discontinuing therapy during pregnancy should be based on a shared decision-making process (Gramegna 2024).
Elexacaftor, tezacaftor, and ivacaftor are present in breast milk (Collins 2022; Jain 2022; Ripani 2023).
Data related to the presence of elexacaftor, tezacaftor, and ivacaftor in breast milk are available following maternal use of this combination in one patient during pregnancy and postpartum. Treatment with elexacaftor 100 mg, tezacaftor 50 mg, and ivacaftor 75 mg daily in combination with ivacaftor 150 mg/day was initiated prior to pregnancy, discontinued once pregnancy was reported, then restarted at 12 weeks' gestation. Sampling occurred 3 months postpartum, prior to the morning dose. Elexacaftor concentrations were 1,185.2 ± 114.01 ng/mL (maternal plasma), 1,049.07 ± 68.77 ng/mL (breast milk), and 4.66 ± 1.15 ng/mL (infant plasma). Tezacaftor concentrations were 1,017.57 ± 80.02 ng/mL (maternal plasma), 761.3 ± 22.62 ng/mL (breast milk), and 13.91 ± 2.25 ng/mL (infant plasma). Ivacaftor concentrations were 1,071.5 ± 80.12 ng/mL (maternal plasma), 1,794.50 ± 4.95 ng/mL (breast milk), and 23.93 ± 2.95 ng/mL (infant plasma). No relevant adverse events were observed in the exclusively breastfed infant; blood tests and eye exams were normal (Ripani 2023).
Bilateral cataracts were observed in 3 infants exposed to elexacaftor/tezacaftor/ivacaftor in utero and via breast milk. Ophthalmic exams were done at 8 weeks of age in 2 infants and 6 months of age in the third. Cataracts were reported to be mild without significant visual impairment (Jain 2022). Additional outcome data following maternal use of this combination while breastfeeding are limited (Collins 2022; Kendle 2021; Metcalf 2024; Taylor-Cousar 2021).
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. Safety data related to the use of variant specific cystic fibrosis transmembrane conductance regulator (CFTR) therapy while breastfeeding are limited (Southern 2023). Monitoring of liver function and ophthalmic exams is recommended in infants exposed to CFTR therapy via breast milk (Southern 2023).
Take with fat-containing food (eg, eggs, butter, peanut butter, whole-milk dairy products [eg, whole milk, cheese, yogurt]). Avoid food or drink containing grapefruit during treatment.
LFTs (ALT, AST, alkaline phosphatase, and bilirubin) at baseline, every month during the first 6 months, then every 3 months for the next 12 months, then annually thereafter (consider more frequent monitoring in patients with history of liver disease or elevated LFT at baseline). Baseline and follow-up ophthalmological examinations are recommended in pediatric patients.
Elexacaftor and tezacaftor facilitate the cellular processing and trafficking of normal and select mutant forms of cystic fibrosis transmembrane conductance regulator (CFTR) (including F508del-CFTR) to increase the amount of mature CFTR protein delivered to the cell surface.
Ivacaftor is a CFTR potentiator that facilitates increased chloride transport by potentiating the channel-open probability (or gating) of the CFTR protein at the cell surface.
Note: The following pharmacokinetic parameters are based on studies in patients with cystic fibrosis ≥12 years of age and adults. Exposures in children ≥6 years are within the range shown in patients ≥12 years.
Absorption:
Elexacaftor: AUC increased 1.9- to 2.5-fold with a moderate-fat meal.
Ivacaftor: Food increases exposure 2.5- to 4-fold.
Tezacaftor: No significant effect from food.
Distribution:
Elexacaftor: 53.7 ± 17.7 L.
Ivacaftor: 293 ± 89.8 L.
Tezacaftor: 82 ± 22.3 L.
Protein binding:
Elexacaftor: >99%.
Ivacaftor: ~99%.
Tezacaftor: ~99%.
Metabolism:
Elexacaftor: Primarily via CYP3A4/5 to active metabolite M23-ELX (similar potency to parent compound).
Ivacaftor: Primarily via CYP3A4/5 to active metabolite M1-IVA (significantly less potent compared to parent compound).
Tezacaftor: Primarily via CYP3A4/5 to active metabolite M1-TEZ (similar potency to parent compound).
Bioavailability:
Elexacaftor: 80%.
Ivacaftor: Not determined.
Tezacaftor: Not determined.
Half-life elimination:
Elexacaftor: 27.4 ± 9.31 hours.
Ivacaftor: 15 ± 3.92 hours.
Tezacaftor: 25.1 ± 4.93 hours.
Time to peak:
Elexacaftor: Median: 6 hours (range: 4 to 12 hours).
Ivacaftor: Median: 4 hours (range: 3 to 6 hours).
Tezacaftor: Median: 3 hours (range: 2 to 4 hours).
Excretion:
Elexacaftor: Urine (0.23%); feces (~87% primarily as metabolites).
Ivacaftor: Urine (6.6%); feces (~88%).
Tezacaftor: Urine (14%, <1% as unchanged drug); feces (72% as unchanged drug or M2-TEZ metabolite).
Hepatic impairment: In patients with moderate impairment (Child-Turcotte-Pugh class B), elexacaftor AUC and Cmax increased 25% and 12%, respectively; M23-ELX AUC and Cmax increased 73% and 70%, respectively; combined elexacaftor and M23-ELX AUC and Cmax increased 36% and 24%, respectively; tezacaftor AUC increased 20% but Cmax similar; and ivacaftor AUC increased 1.5-fold and Cmax increased 10% compared to healthy subjects.
