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Tezacaftor and ivacaftor: Drug information

Tezacaftor and ivacaftor: Drug information
2024© UpToDate, Inc. and its affiliates and/or licensors. All Rights Reserved.
For additional information see "Tezacaftor and ivacaftor: Patient drug information" and "Tezacaftor and ivacaftor: Pediatric drug information"

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

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

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.

Dosing: Kidney Impairment: Adult

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.

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): 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.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Tezacaftor and ivacaftor: Pediatric drug information")

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

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.

Dosing: Kidney Impairment: Pediatric

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.

Dosing: Hepatic Impairment: Pediatric

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.

Adverse Reactions

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)

Contraindications

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

Canadian labeling: Hypersensitivity to ivacaftor, tezacaftor, 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 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.

Dosage Forms: US

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)]

Generic Equivalent Available: US

No

Pricing: US

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.

Dosage Forms: Canada

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)]

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 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.

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 or Seville oranges.

Use: Labeled Indications

Cystic fibrosis: Treatment of patients with cystic fibrosis ≥6 years of age who are homozygous for the F508del mutation or who 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.

Note: A list of CFTR gene mutations that produce CFTR protein and are responsive to tezacaftor/ivacaftor include: A455E, A1067T, D110E, D110H, D579G, D1152H, D1270N, E56K, E193K, E831X, F1052V, F1074L, F508del (two copies of mutation or at least 1 copy of a responsive mutation), K1060T, L206W, P67L, R74W, R1070W, R117C, R347H, R352Q, 51070W, S945L, S977F, 711+3A→G, 2789+5G→A, 3272-26A→G, 3849+10kbC→T.

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 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 CYP3A4 Substrates (High risk with Inhibitors). 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: 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 the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy

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

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

CYP3A4 Inhibitors (Moderate): May increase the 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 the 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 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). 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 the serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor therapy

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

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

Grapefruit Juice: May increase the serum concentration of Tezacaftor and Ivacaftor. Risk X: Avoid combination

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: May increase the serum concentration of Tezacaftor and Ivacaftor. Tezacaftor and Ivacaftor may increase the 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 the serum concentration of Mavorixafor. Risk C: Monitor therapy

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

Pralsetinib: P-glycoprotein/ABCB1 Inhibitors may increase the 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 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

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

Rifabutin: May decrease the serum concentration of 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 Tezacaftor and Ivacaftor. 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 (Withdrawn from US Market): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tegaserod (Withdrawn from US Market). 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: Tezacaftor and Ivacaftor may increase the serum concentration of Warfarin. Risk C: Monitor therapy

Food Interactions

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.

Pregnancy Considerations

Ivacaftor crosses the placenta (Trimble 2018).

Refer to the ivacaftor monograph for additional information.

Breastfeeding Considerations

Ivacaftor is present in breast milk (Trimble 2018); excretion of 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. Refer to the ivacaftor monograph for additional information.

Dietary Considerations

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.

Monitoring Parameters

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).

Mechanism of Action

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.

Pharmacokinetics (Adult Data Unless Noted)

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)

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

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.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AR) Argentina: Tezacar;
  • (AT) Austria: Symkevi;
  • (AU) Australia: Symdeko;
  • (BE) Belgium: Symkevi;
  • (BR) Brazil: Symdeko;
  • (CH) Switzerland: Symdeko;
  • (CO) Colombia: Symdeko;
  • (CZ) Czech Republic: Symkevi;
  • (DE) Germany: Symkevi;
  • (ES) Spain: Symkevi;
  • (FI) Finland: Symkevi;
  • (FR) France: Symkevi;
  • (GB) United Kingdom: Symkevi;
  • (IE) Ireland: Symkevi;
  • (IT) Italy: Symkevi;
  • (LU) Luxembourg: Symkevi;
  • (NL) Netherlands: Symkevi;
  • (NO) Norway: Symkevi;
  • (PL) Poland: Symkevi;
  • (PR) Puerto Rico: Symdeko;
  • (PT) Portugal: Symkevi;
  • (RU) Russian Federation: Symdeko;
  • (SE) Sweden: Symkevi;
  • (SK) Slovakia: Symkevi
  1. Symdeko (tezacaftor/ivacaftor) [prescribing information]. Boston, MA: Vertex Pharmaceuticals Incorporated; August 2023.
  2. Symdeko (tezacaftor/ivacaftor) [product monograph]. Toronto, Ontario, Canada: Vertex Pharmaceuticals (Canada) Incorporated; August 2020.
  3. Trimble A, McKinzie C, Terrell M, et al. 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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