Version July 2025
Note: Symdeko is supplied as two separate products packaged together: tezacaftor/ivacaftor tablets in a fixed-dose combination and ivacaftor tablets; use caution when selecting dosage form; multiple strengths are available.
Cystic fibrosis:
Children ≥6 years to <12 years weighing <30 kg: Oral: Tezacaftor 50 mg/ivacaftor 75 mg (1 tablet) in the morning and ivacaftor 75 mg in the evening, approximately 12 hours apart.
Children ≥6 years to <12 years weighing ≥30 kg, Children ≥12 years, and Adolescents: Oral: Tezacaftor 100 mg/ivacaftor 150 mg (1 tablet) in the morning and ivacaftor 150 mg in the evening, approximately 12 hours apart.
Missed dose: If a dose is missed ≤6 hours of the usual time it is taken, take the dose as soon as possible; if >6 hours has passed since the missed dose, skip the missed dose and resume the normal dosing schedule.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl >30 mL/minute: No dosage adjustment necessary.
CrCl ≤30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use with caution.
ESRD: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use with caution.
Hepatic impairment prior to initiation (baseline): Oral:
Mild impairment: Children ≥6 years and Adolescents: No dosage adjustment necessary.
Moderate impairment:
Children 6 years to <12 years weighing <30 kg: Tezacaftor 50 mg/ivacaftor 75 mg once daily in the morning. The evening dose of ivacaftor 75 mg should not be administered.
Children ≥6 years to <12 years weighing ≥30 kg, Children ≥12 years, and Adolescents: Tezacaftor 100 mg/ivacaftor 150 mg once daily in the morning. The evening dose of ivacaftor 150 mg should not be administered.
Severe impairment:
Children ≥6 years to <12 years weighing <30 kg: Tezacaftor 50 mg/ivacaftor 75 mg once daily in the morning (or less frequently). The evening dose of ivacaftor 75 mg should not be administered.
Children ≥6 years to <12 years weighing ≥30 kg, Children ≥12 years, and Adolescents: Tezacaftor 100 mg/ivacaftor 150 mg once daily in the morning (or less frequently). The evening dose of ivacaftor 150 mg should not be administered.
Hepatotoxicity during treatment: Children ≥6 years and Adolescents:
ALT or AST >5 × ULN without concomitant elevated bilirubin: Temporarily discontinue 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 tezacaftor/ivacaftor; may resume if elevated transaminases are resolved and after assessing benefits versus risks of continued treatment.
(For additional information see "Tezacaftor and ivacaftor co-packaged with ivacaftor: Drug information")
Note: Symdeko is supplied as copackaged tezacaftor 100 mg/ivacaftor 150 mg fixed-dose combination (yellow) tablets and ivacaftor 150 mg (light blue) tablets.
Cystic fibrosis: Oral: Tezacaftor 100 mg/ivacaftor 150 mg in the morning and ivacaftor 150 mg in the evening, ~12 hours apart.
Missed dose: If a dose is missed ≤6 hours of the usual time it is taken, take the dose as soon as possible; if >6 hours has passed since the missed dose, skip the missed dose and resume the normal dosing schedule.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl >30 mL/minute: No dosage adjustment necessary.
CrCl ≤30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use with caution.
ESRD: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use with caution.
Hepatic impairment prior to treatment initiation:
Mild impairment (Child-Pugh class A): No dosage adjustment necessary.
Moderate impairment (Child-Pugh class B): Tezacaftor 100 mg/ivacaftor 150 mg once daily in the morning. The evening dose of ivacaftor 150 mg should not be administered.
Severe impairment (Child-Pugh class C): Tezacaftor 100 mg/ivacaftor 150 mg once daily in the morning (or less frequently). The evening dose of ivacaftor 150 mg should not be administered.
Hepatotoxicity during treatment:
ALT or AST >5 × ULN without concomitant elevated bilirubin: Temporarily discontinue tezacaftor/ivacaftor; may resume if elevated transaminases resolved and after assessing benefits versus risks of continued treatment.
ALT or AST >3 × ULN with concomitant bilirubin >2 × ULN: Temporarily discontinue tezacaftor/ivacaftor; may resume if elevated transaminases resolved and after assessing benefits versus risks of continued treatment.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in children, adolescents, and adults. Also see Ivacaftor.
>10%: Nervous system: Headache (15%)
1% to 10%:
Gastrointestinal: Nausea (9%)
Nervous system: Dizziness (4%)
Respiratory: Paranasal sinus congestion (4%)
<1%: Gastrointestinal: Gastrointestinal obstruction
Postmarketing:
Dermatologic: Skin rash
Hypersensitivity: Hypersensitivity reaction (including anaphylaxis)
Ophthalmic: Cataract (children)
There are no contraindications listed in the US manufacturer's labeling.
Canadian labeling: Hypersensitivity to ivacaftor, tezacaftor, or any component of the formulation.
Concerns related to adverse effects:
• Cataracts: Noncongenital lens opacities and cataracts have been reported in pediatric patients treated with tezacaftor/ivacaftor and ivacaftor; other risk factors were present in some cases (eg, corticosteroid use, exposure to radiation), but a possible risk related to tezacaftor/ivacaftor cannot be excluded. Baseline and follow-up ophthalmological examinations are recommended in pediatric patients.
• CNS effects: May cause dizziness, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery, driving).
• Hepatic effects: May increase hepatic transaminases. Monitor ALT, AST, and bilirubin at baseline, every 3 months for the first year of therapy, and annually thereafter; increased monitoring may be necessary in patients with a history of elevated hepatic transaminases. Temporarily discontinue treatment if ALT or AST >5 times ULN or if ALT or AST >3 times ULN with concomitant bilirubin >2 times ULN. Following resolution of transaminase elevations, consider the benefits and risks of resuming therapy.
• Hypersensitivity reactions: Hypersensitivity reactions, including anaphylaxis, have been reported with tezacaftor/ivacaftor use. If signs and symptoms of severe hypersensitivity occur, discontinue use and treat appropriately; consider risk vs 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 to severe (Child-Pugh class B or C) impairment.
• Renal impairment: Use with caution in patients with severe impairment (CrCl ≤30 mL/minute) or ESRD.
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 a CFTR mutation followed by verification with bidirectional sequencing when recommended by the mutation test instructions for use.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet Therapy Pack, Oral:
Symdeko: Tezacaftor 50 mg and ivacaftor 75 mg (28s); Ivacator 75 mg (28s) (56 ea); Tezacaftor 100 mg and ivacaftor 150 mg (28s); Ivacaftor 150 mg (28s) (56 ea) [contains fd&c blue #2 (indigotine,indigo carmine)]
No
Tablet Therapy Pack (Symdeko Oral)
50-75 & 75 mg (per each): $533.23
100-150 & 150 mg (per each): $533.23
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:
Symdeko: Tezacaftor 100 mg and ivacaftor 150 mg (28s); Ivacaftor 150 mg (28s) (56 ea) [contains fd&c blue #2 (indigotine,indigo carmine)]
Product is only available via authorized pharmacies and distributors. Further information is available at https://www.vrtx.com/authorized-distributors.
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 or Seville oranges.
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 or Seville oranges.
Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
Treatment of cystic fibrosis (CF) in patients who are homozygous for the F508del mutation or have at least one mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that is responsive to tezacaftor/ivacaftor based on in vitro data and/or clinical evidence (FDA approved in ages ≥6 years and adults). If the patient's genotype is unknown, an FDA-cleared CF mutation test should be used to detect the presence of the F508del mutation, followed by verification with bidirectional sequencing when recommended by the mutation test instructions for use.
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.
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
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 CYP3A4 Substrates (High risk with Inhibitors). 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 Tezacaftor and Ivacaftor. Risk C: Monitor
CYP3A4 Inducers (Strong): May decrease serum concentration of Tezacaftor and Ivacaftor. Risk X: Avoid
CYP3A4 Inhibitors (Moderate): May increase serum concentration of Tezacaftor and Ivacaftor. Management: If combined with moderate CYP3A4 inhibitors, give tezacaftor/ivacaftor in the morning, every other day; give ivacaftor in the morning, every other day on alternate days. Tezacaftor/ivacaftor dose depends on age and weight; see full Lexi-Interact monograph Risk D: Consider Therapy Modification
CYP3A4 Inhibitors (Strong): May increase serum concentration of Tezacaftor and Ivacaftor. Management: If combined with strong CYP3A4 inhibitors, tezacaftor/ivacaftor should be administered in the morning, twice a week, approximately 3 to 4 days apart. Tezacaftor/ivacaftor dose depends on age and weight; see full Lexi-Interact 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: Tezacaftor and Ivacaftor may increase serum concentration of Glimepiride. Risk C: Monitor
GlipiZIDE: Tezacaftor and Ivacaftor may increase serum concentration of GlipiZIDE. Risk C: Monitor
Grapefruit Juice: May increase serum concentration of Tezacaftor and Ivacaftor. Risk X: Avoid
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: May increase serum concentration of Tezacaftor and Ivacaftor. Tezacaftor and Ivacaftor may increase serum concentration of Lefamulin. Management: Consider alternatives to this combination when possible. If combined, monitor for increased lefamulin toxicities and decrease the 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
PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of PAZOPanib. Risk X: Avoid
Phenobarbital-Primidone: May decrease serum concentration of 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
Repotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Repotrectinib. Risk X: Avoid
Rifabutin: May decrease serum concentration of 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 Tezacaftor and Ivacaftor. 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: Tezacaftor and Ivacaftor may increase serum concentration of Warfarin. Risk C: Monitor
Food increases exposure to tezacaftor/ivacaftor. Tezacaftor/ivacaftor serum concentrations may be increased when taken with grapefruit or Seville oranges. Management: Administer with fat-containing food; avoid grapefruit and Seville oranges during therapy.
Take with fat-containing food (eg, eggs, butter, cheese, nuts, peanut butter, cheese pizza, meats, whole-milk dairy products [eg, whole milk, cheese, yogurt]). Avoid food or drink containing grapefruit or Seville oranges 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).
Ivacaftor and tezacaftor cross the placenta (Collins 2022; Trimble 2018).
Data related to the safety of variant specific cystic fibrosis transmembrane conductance regulator (CFTR) therapy during pregnancy are limited (Southern 2023) and outcome data specific to this dual therapy combination are limited (Nash 2020).
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). Available data are limited (based on a study conducted with ivacaftor and tezacaftor in combination with elexacaftor) and show high interpatient variability. Dose adjustments based on routine clinical monitoring and therapeutic drug monitoring may be needed (Christina 2024). 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).
CF mutation test (prior to therapy if genotype is unknown); ophthalmological examinations (baseline and follow-up in pediatric patients); ALT and AST (baseline, every 3 months for the first year of therapy, and annually thereafter; increased monitoring may be necessary in patients with a history of elevated hepatic transaminases or bilirubin)
Tezacaftor: Facilitates the cellular processing and trafficking of normal and select mutant forms of CFTR (including F508del-CFTR) to increase the amount of mature CFTR protein delivered to the cell surface.
Ivacaftor: CFTR potentiator that facilitates increased chloride transport by potentiating the channel-open probability (or gating) of the CFTR protein at the cell surface.
Absorption: Ivacaftor and tezacaftor: Variable; increased (by ~3-fold) when administered with fatty foods compared with fasting.
Distribution: Vd:
Ivacaftor: 206 L ± 82.9 L
Tezacaftor: 271 L ± 157 L
Protein binding:
Ivacaftor: ~99%; primarily to alpha1-acid glycoprotein and albumin
Tezacaftor: ~99%; primarily to albumin
Metabolism:
Ivacaftor: Hepatic; extensive via CYP3A and CYP3A5; forms 2 major metabolites (M1 [active; 1/6 potency] and M6 [inactive])
Tezacaftor: Hepatic; extensive via CYP3A and CYP3A5; forms 3 major metabolites (M1 and M2 active; M5 inactive)
Half-life elimination:
Ivacaftor: 13.7 ± 6.06 hours
Tezacaftor: 15 ± 3.44 hours
Time to peak:
Ivacaftor: Median: ~6 hours (range: 3 to 10 hours)
Tezacaftor: Median: ~4 hours (range: 2 to 6 hours)
Excretion:
Ivacaftor: Feces (87.8%); urine (6.6%)
Tezacaftor: Feces (72% as unchanged drug or M2 metabolite); urine (14% [mostly as M2 metabolite], <1% of administered dose as unchanged drug)
Hepatic function impairment: AUC was ~36% higher and Cmax was ~10% higher for tezacaftor, and a 1.5- to 2-fold increase in ivacaftor AUC in patients with moderate hepatic impairment.
Pediatric: Exposure (AUC) in pediatric patients (6 to <18 years of age) is similar to adult patients.
