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Elexacaftor, tezacaftor, and ivacaftor co-packaged with ivacaftor: Drug information

Elexacaftor, tezacaftor, and ivacaftor co-packaged with ivacaftor: Drug information
(For additional information see "Elexacaftor, tezacaftor, and ivacaftor co-packaged with ivacaftor: Pediatric drug information" and see "Elexacaftor, tezacaftor, and ivacaftor co-packaged with ivacaftor: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Trikafta
Brand Names: Canada
  • Trikafta
Pharmacologic Category
  • Cystic Fibrosis Transmembrane Conductance Regulator Corrector;
  • Cystic Fibrosis Transmembrane Conductance Regulator Potentiator
Dosing: Adult

Note: 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

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

Dosing: Kidney Impairment: Adult

eGFR ≥30 mL/min/1.73 m2: No dosage adjustment necessary.

eGFR <30 mL/min/1.73 m2: There are no specific dosage adjustments provided in the manufacturer's labeling (has not been studied); use with caution.

Dosing: Hepatic Impairment: Adult

Hepatic impairment prior to treatment initiation:

Mild impairment (Child-Pugh class A): No dosage adjustment necessary.

Moderate impairment (Child-Pugh class B): Use only if the benefits outweigh the risks.

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-Pugh class C): Use not recommended (has not been studied).

Hepatotoxicity during treatment: ALT/AST >5 × ULN or ALT/AST >3 × ULN with bilirubin >2 × ULN: Interrupt therapy until resolved; consider the benefits and risks prior to resuming.

Dosing: Pediatric

(For additional information see "Elexacaftor, tezacaftor, and ivacaftor co-packaged with ivacaftor: Pediatric drug information")

Note: Trikafta is supplied as 2 separate products packaged together: Elexacaftor/tezacaftor/ivacaftor in a fixed-dose combination and ivacaftor; use caution when selecting dosage form; multiple strengths are available; appropriate strength is dependent on patient age and weight.

Cystic fibrosis

Cystic fibrosis (CF):

Elexacaftor 50 mg/tezacaftor 25 mg/ivacaftor 37.5 mg per tablet:

Children ≥6 years to <12 years weighing <30 kg: Oral: 2 tablets (elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg) in the morning and ivacaftor 75 mg in the evening, approximately 12 hours apart.

Elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg per tablet:

Children ≥6 years to <12 years weighing ≥30 kg or Children ≥12 years and Adolescents: Oral: 2 tablets (elexacaftor 200 mg/tezacaftor 100 mg/ivacaftor 150 mg) in the morning and ivacaftor 150 mg 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.

Dosing: Kidney Impairment: Pediatric

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.

Dosing: Hepatic Impairment: Pediatric

Note: Use caution when selecting dosage form; multiple strengths are available.

Hepatic impairment prior to initiation (baseline):

Mild impairment (Child-Pugh class A): Children ≥ 6 years and Adolescents: Oral: No dosage adjustment necessary.

Moderate impairment (Child-Pugh class B): Note: Use not recommended unless benefits exceed the risk.

Children ≥6 years to <12 years weighing <30 kg:

Elexacaftor 50 mg/tezacaftor 25 mg/ivacaftor 37.5 mg per tablet:

Day 1: Oral: 2 tablets elexacaftor/tezacaftor/ivacaftor once in the morning; omit the evening dose of ivacaftor.

Day 2: Oral: 1 tablet elexacaftor/tezacaftor/ivacaftor 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 ≥6 years to <12 years weighing ≥30 kg or Children ≥12 years and Adolescents:

Elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg per tablet.

Day 1: Oral: 2 tablets elexacaftor/tezacaftor/ivacaftor once in the morning; omit the evening dose of ivacaftor.

Day 2: Oral: 1 tablet elexacaftor/tezacaftor/ivacaftor 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 (Child-Pugh class C): Children ≥6 years and Adolescents: Oral: Do not administer; use has not been studied.

Hepatotoxicity during treatment: Children ≥6 years and Adolescents: Oral:

ALT or AST >5 × ULN: Temporarily discontinue elexacaftor/tezacaftor/ivacaftor; may resume if elevated transaminases are resolved and after assessing benefits versus risks of continued treatment.

ALT or AST >3 × ULN with concomitant bilirubin >2 × ULN: Temporarily discontinue elexacaftor/tezacaftor/ivacaftor; may resume if elevated transaminases are resolved and after assessing benefits versus risks of continued treatment.

Dosing: Older Adult

Has not been studied.

Dosage Forms: US

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)]

Generic Equivalent Available: US

No

Dosage Forms: Canada

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]

Prescribing and Access Restrictions

Product is only available via authorized pharmacies and distributors. Further information is available at https://www.vrtx.com/authorized-distributors.

Administration: Adult

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, whole milk, or meats).

Administration: Pediatric

Oral: Swallow tablet whole. Administer with fat-containing food (eg, eggs, butter, oils, cheese, nuts, peanut butter, meats, whole-milk dairy products). Avoid food or drink containing grapefruit.

Use: Labeled Indications

Cystic fibrosis: Treatment of cystic fibrosis in patients ≥6 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 in vitro data.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults and adolescents. Also see Tezacaftor and Ivacaftor, and Ivacaftor.

>10%:

Gastrointestinal: Abdominal pain (14%), diarrhea (13%)

Hepatic: Increased indirect serum bilirubin (11%)

Nervous system: Headache (17%)

Respiratory: Upper respiratory tract infection (16%)

1% to 10%:

Cardiovascular: Increased blood pressure (4%)

Dermatologic: Acne vulgaris (2% to 5%), eczema (2% to 5%), pruritus (2% to 5%), skin rash (10%; females 16%, males 5%)

Endocrine & metabolic: Hypoglycemia (2% to 5%)

Gastrointestinal: Abdominal distention (2% to 5%), 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 alanine aminotransferase (10%), increased serum aspartate aminotransferase (9%), increased serum bilirubin (5%)

Infection: Influenza (7%)

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 (7%), rhinorrhea (8%), sinusitis (5%), tonsillitis (2% to 5%)

Postmarketing: Hepatic: Hepatic failure, liver injury

Contraindications

There are no contraindications listed in the manufacturer's US labeling.

Canadian labeling: Hypersensitivity to elexacaftor, tezacaftor, ivacaftor, or any component of the formulation.

Warnings/Precautions

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.

• Hepatic effects: Liver failure leading to transplantation in patients with cirrhosis and portal hypertension has been reported; avoid use when possible in patients with preexisting liver disease (eg, presence of cirrhosis, portal hypertension, ascites, hepatic encephalopathy). Increased LFTs, sometimes requiring hospital intervention, may occur even in patients without preexisting liver disease.

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/min/1.73 m2).

Other warnings/precautions:

• Appropriate use: If the patient's genotype is unknown, an FDA-cleared CF mutation test should be used to detect the presence of at least one F508del mutation or a mutation that is responsive based on in vitro data.

Metabolism/Transport Effects

Substrate of BCRP/ABCG2, CYP3A4 (major), OATP1B1/1B3 (SLCO1B1/1B3), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits P-glycoprotein/ABCB1

Drug Interactions

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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the 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 the serum concentration of Aliskiren. Risk C: Monitor therapy

Berotralstat: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Berotralstat. Management: Decrease the berotralstat dose to 110 mg daily when combined with P-glycoprotein (P-gp) inhibitors. Risk D: Consider therapy modification

Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bilastine. Risk X: Avoid combination

Celiprolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Celiprolol. Risk C: Monitor therapy

Clofazimine: May increase the serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Risk C: Monitor therapy

Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a P-gp inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. See interaction monograph for details. Risk D: Consider therapy modification

CycloSPORINE (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Risk X: Avoid combination

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Management: When combined with moderate CYP3A4 inhibitors, two elexacaftor/tezacaftor/ivacaftor (100 mg/50 mg/75 mg) tablets should be given in the morning, every other day. Ivacaftor (150 mg) should be given in the morning, every other day on alternate days. Risk D: Consider therapy modification

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Management: When combined with strong CYP3A4 inhibitors, administer two elexacaftor/tezacaftor/ivacaftor tablets (100 mg/50 mg/75 mg) in the morning, twice a week, approximately 3 to 4 days apart. No evening doses of ivacaftor (150 mg) alone should be administered. Risk D: Consider therapy modification

Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Risk C: Monitor therapy

Digoxin: P-glycoprotein/ABCB1 Inhibitors may increase the 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 the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination

DOXOrubicin (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Liposomal). Risk C: Monitor therapy

Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Risk C: Monitor therapy

Etoposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide. Risk C: Monitor therapy

Etoposide Phosphate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide Phosphate. Risk C: Monitor therapy

Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. Risk C: Monitor therapy

Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Glecaprevir and Pibrentasvir: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor therapy

Glimepiride: Elexacaftor, Tezacaftor, and Ivacaftor may increase the serum concentration of Glimepiride. Risk C: Monitor therapy

GlipiZIDE: Elexacaftor, Tezacaftor, and Ivacaftor may increase the serum concentration of GlipiZIDE. Risk C: Monitor therapy

Grapefruit Juice: May increase the serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Specifically, the serum concentration of ivacaftor may be increased. Risk X: Avoid combination

Hormonal Contraceptives: May enhance the adverse/toxic effect of Elexacaftor, Tezacaftor, and Ivacaftor. Specifically, the risk for rash may be increased. Risk C: Monitor therapy

Lapatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Lapatinib. Risk C: Monitor therapy

Larotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Larotrectinib. Risk C: Monitor therapy

Lefamulin: Elexacaftor, Tezacaftor, and Ivacaftor may increase the serum concentration of Lefamulin. Lefamulin may increase the 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

Morphine (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Morphine (Systemic). Risk C: Monitor therapy

Nadolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Nadolol. Risk C: Monitor therapy

Naldemedine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naldemedine. Risk C: Monitor therapy

Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol. Risk C: Monitor therapy

PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib. Risk X: Avoid combination

Ranolazine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ranolazine. Risk C: Monitor therapy

Relugolix: P-glycoprotein/ABCB1 Inhibitors may increase the 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

Relugolix, Estradiol, and Norethindrone: P-glycoprotein/ABCB1 Inhibitors may increase the 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

Rifabutin: May decrease the serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Specifically, the serum concentration of ivacaftor may be decreased. Risk C: Monitor therapy

RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. Risk C: Monitor therapy

Rimegepant: P-glycoprotein/ABCB1 Inhibitors may increase the 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 the serum concentration of RisperiDONE. Risk C: Monitor therapy

RomiDEPsin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RomiDEPsin. Risk C: Monitor therapy

Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. Risk C: Monitor therapy

Sirolimus (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the 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 the serum concentration of Sirolimus (Protein Bound). Risk X: Avoid combination

St John's Wort: May decrease the serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Specifically, the serum concentration of ivacaftor may be decreased. Risk X: Avoid combination

Tacrolimus (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy

Talazoparib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Talazoparib. Risk C: Monitor therapy

Tegaserod: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tegaserod. Risk C: Monitor therapy

Teniposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Teniposide. Risk C: Monitor therapy

Tenofovir Disoproxil Fumarate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor therapy

Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. Risk X: Avoid combination

Ubrogepant: P-glycoprotein/ABCB1 Inhibitors may increase the 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 the 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 (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal). Risk X: Avoid combination

Warfarin: Elexacaftor, Tezacaftor, and Ivacaftor may increase the serum concentration of Warfarin. Risk C: Monitor therapy

Food Interactions

Grapefruit juice may increase exposure of elexacaftor, tezacaftor, or ivacaftor. Management: Avoid food or drink containing grapefruit during treatment.

Pregnancy Considerations

Ivacaftor crosses the placenta (Trimble 2018).

Also refer to the ivacaftor monograph for additional information.

Breastfeeding Considerations

Ivacaftor is present in breast milk (Trimble 2018); excretion of elexacaftor and tezacaftor is not known.

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.

Also refer to the ivacaftor monograph for additional information.

Dietary Considerations

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.

Monitoring Parameters

LFTs at baseline, every 3 months during the first year, then annually thereafter (more frequent monitoring should be considered in patients with cirrhosis, portal hypertension, or a history of hepatobiliary disease or LFT elevations). Baseline and follow-up ophthalmological examinations are recommended in pediatric patients.

Mechanism of Action

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.

Pharmacokinetics

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).

Pharmacokinetics: Additional Considerations

Hepatic impairment: In patients with moderate impairment (Child-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.

Pricing: US

Tablet Therapy Pack (Trikafta Oral)

50-25-37.5 & 75 mg (per each): $358.10

100-50-75 & 150 mg (per each): $358.10

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.

Brand Names: International
  • Kaftrio (AT, CZ, DE, DK, EE, FR, GB, HR, HU, LT, LV, NL, PT, SK);
  • Trikafta (AU)


For country code abbreviations (show table)
  1. Trikafta (elexacaftor/tezacaftor/ivacaftor) [prescribing information]. Boston, MA: Vertex Pharmaceuticals Incorporated; October 2021.
  2. Trikafta (elexacaftor/tezacaftor/ivacaftor) [product monograph]. Toronto, Ontario, Canada: Vertex Pharmaceuticals (Canada) Inc; April 2022.
  3. Trimble A, McKinzie C, Terrell M, Stringer E, Esther CR Jr. Measured fetal and neonatal exposure to lumacaftor and ivacaftor during pregnancy and while breastfeeding. J Cyst Fibros. 2018;17(6):779-782. doi: 10.1016/j.jcf.2018.05.009. [PubMed 29866531]
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