Tezacaftor

Identification

Summary

Tezacaftor is a medication used to treat homozygous or heterozygous F508del mutation cystic fibrosis.

Brand Names
Symdeko, Trikafta (100 Mg / 50 Mg / 75 Mg; 150 Mg)
Generic Name
Tezacaftor
DrugBank Accession Number
DB11712
Background

Tezacaftor is a drug of the cystic fibrosis transmembrane conductance regulator (CFTR) potentiator class.10 It was developed by Vertex Pharmaceuticals and FDA approved in combination with ivacaftor to manage cystic fibrosis.14 This drug was approved by the FDA on February 12, 2018.15

Cystic Fibrosis is an autosomal recessive disorder caused by one of several different mutations in the gene for the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein, an ion channel involved in the transport of chloride and sodium ions across cell membranes. CFTR is active in epithelial cells of organs such as of the lungs, pancreas, liver, digestive system, and reproductive tract. Alterations in the CFTR gene result in altered production, misfolding, or function of the protein and consequently abnormal fluid and ion transport across cell membranes.5,6 As a result, CF patients produce thick, sticky mucus that clogs the ducts of organs where it is produced making patients more susceptible to complications such as infections, lung damage, pancreatic insufficiency, and malnutrition.7

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 520.505
Monoisotopic: 520.182121086
Chemical Formula
C26H27F3N2O6
Synonyms
  • Tezacaftor
External IDs
  • VX 661
  • VX-661
  • VX661

Pharmacology

Indication

Tezacaftor is combined with ivacaftor in one product for the treatment of cystic fibrosis (CF) in patients aged 12 years or older with two copies of the F508del gene mutation or at least one mutation in the CFTR gene that is responsive to this drug.14

Tezacaftor, when used in combination with ivacaftor and elexacaftor in the product Trikafta, is also indicated for the treatment of CF in patients 12 years of age and older that have at least one F508del mutation in the CFTR gene.19

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Used in combination to manageCystic fibrosisCombination Product in combination with: Ivacaftor (DB08820), Elexacaftor (DB15444)•••••••••••••••••••
Used in combination to manageCystic fibrosisCombination Product in combination with: Elexacaftor (DB15444), Ivacaftor (DB08820)••••••••••••••••••
Used in combination to treatCystic fibrosisCombination Product in combination with: Ivacaftor (DB08820)•••••••••••••• ••••• ••• •••••••• •• ••• •••••• •••••••• ••••••••••••• ••••••••••• ••••••••• •••••• •••• •••• •• •••••••••• •• ••••••••••••••••••••
Used in combination to treatCystic fibrosisCombination Product in combination with: Ivacaftor (DB08820)•••••••••••••••••• ••••••••• •••••••••• ••• ••• ••••••• •••• ••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Clinical studies have shown a significant decrease in sweat chloride and an increase in the forced expiratory volume (FEV), a measure of lung function, following Tevacaftor/Ivacaftor therapy.1 Phase 3 clinical studies have shown that a significant increase in forced expiratory volume was attained at 4 and 8 weeks after initiating this drug. The above effects lead to improvement of the respiratory symptoms of cystic fibrosis. Tezacaftor does not induce clinically significant QT prolongation.2 When given with ivacaftor, tezacaftor can lead to liver transaminase elevations.14 Testing of transaminases (ALT and AST) levels should occur before starting this combination every 3 months during the first year of treatment, and every year afterwards. Patients with a history of transaminase elevations should be monitored more frequently.14

Mechanism of action

The transport of charged ions across cell membranes is normally achieved through the actions of the cystic fibrosis transmembrane regulator (CFTR) protein. This protein acts as a channel and allows for the passage of chloride and sodium. This process affects the movement of water in and out of the tissues and impacts the production of mucus that lubricates and protects certain organs and body tissues, including the lungs. In the F508del mutation of the CFTR gene, one amino acid is deleted at the position 508, therefore, the CFTR channel function is compromised, resulting in thickened mucus secretions.10 CFTR correctors such as tezacaftor aim to repair F508del cellular misprocessing.9 This is done by modulating the position of the CFTR protein on the cell surface to the correct position, allowing for adequate ion channel formation and increased in water and salt movement through the cell membrane.10 The concomitant use of ivacaftor is intended to maintain an open channel, increasing the transport of chloride, reducing thick mucus production.13

TargetActionsOrganism
ACystic fibrosis transmembrane conductance regulator
positive allosteric modulator
Humans
Absorption

The Cmax, Tmax and AUC of tezacaftor, when administered with ivacaftor, are 5.95 mcg/ml, 2-6 h, and 84.5 mcg.h/ml respectively.14 Exposure of tezacaftor/ivacaftor increases 3-fold when it is administered with a high-fat meal.14

Volume of distribution

The apparent volume of distribution of tezacaftor was 271 L in a study of patients in the fed state who received 100 mg of tezacaftor every 12 hours.14

Protein binding

Tezacaftor is approximately 99% bound to plasma proteins, mainly albumin.14

Metabolism

Tezacaftor is metabolized extensively in humans by the action of CYP3A4 and CYP3A5. There are three main circulating metabolites; M1, M2, and M5. The M1 is an active metabolite with similar activity to the parent drug, tezacaftor. The M2 metabolite is significantly less active and M5 is considered an inactive metabolite.4,14 An additional circulating metabolite, M3, corresponding to the glucuronide form of tezacaftor.14

Hover over products below to view reaction partners

Route of elimination

After oral administration, the majority of tezacaftor dose (72%) is found excreted in the feces either unchanged or as its metabolite, M2. About 14% of the administered dose is found excreted in the urine as the metabolite, M2. It was noted that less than 1% of the administered dose is excreted unchanged in the urine and thus, renal excretion is not the major elimination pathway.14

Half-life

The apparent half-life of tezacaftor is approximately 57.2 hours.4,18

Clearance

The apparent clearance of tezacaftor has been measured at 1.31 L/h for patients in the fed state during a clinical trial.3

Adverse Effects
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Toxicity

The LD50 of an oral dose in rats is >2000 mg/kg.17

Overdose symptoms may include dizziness and diarrhea. There have been no reports to this date of tezacaftor overdose, but the highest dose of 450 mg every 12 hours commonly resulted in reports of dizziness and diarrhea. No antidote exists for treating an overdose with this drug. General supportive measures should be undertaken along with monitoring of vital signs and close monitoring of clinical status.14

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbametapirThe serum concentration of Tezacaftor can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Tezacaftor can be increased when combined with Abatacept.
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with Tezacaftor.
AbrocitinibThe serum concentration of Tezacaftor can be increased when it is combined with Abrocitinib.
AcalabrutinibThe metabolism of Tezacaftor can be decreased when combined with Acalabrutinib.
Food Interactions
  • Avoid grapefruit products. Grapefruit inhibits CYP3A metabolism, which may increase the serum concentration of tezacaftor.
  • Avoid St. John's Wort. This herb induces CYP3A metabolism and may reduce serum levels of tezacaftor.
  • Take with food. Tezacaftor should be taken with fat-containing food to increase exposure.

Products

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
KaftrioTezacaftor (50 mg) + Elexacaftor (100 mg) + Ivacaftor (75 mg)Tablet, film coatedOralVertex Pharmaceuticals (Ireland) Limited2020-12-15Not applicableEU flag
KAFTRIOTezacaftor (50 MG) + Elexacaftor (100 MG) + Ivacaftor (75 MG)Tablet, film coatedOralVertex Pharmaceuticals (Ireland) Limited2020-11-14Not applicableItaly flag
KaftrioTezacaftor (25 mg) + Elexacaftor (50 mg) + Ivacaftor (37.5 mg)Tablet, film coatedOralVertex Pharmaceuticals (Ireland) Limited2022-05-04Not applicableEU flag
SymdekoTezacaftor (100 mg) + Ivacaftor (150 mg) + Ivacaftor (150 mg)TabletOralVertex Pharmaceuticals Incorporated2018-06-28Not applicableCanada flag
SymdekoTezacaftor (100 mg/1) + Ivacaftor (150 mg/1) + Ivacaftor (150 mg/1)Kit; Tablet, film coatedOralVertex Pharmaceuticals Incorporated2018-02-12Not applicableUS flag

Categories

ATC Codes
R07AX32 — Ivacaftor, tezacaftor and elexacaftorR07AX31 — Ivacaftor and tezacaftor
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as n-alkylindoles. These are compounds containing an indole moiety that carries an alkyl chain at the 1-position.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Indoles and derivatives
Sub Class
N-alkylindoles
Direct Parent
N-alkylindoles
Alternative Parents
Indoles / Benzodioxoles / N-arylamides / Substituted pyrroles / Aryl fluorides / Benzenoids / Cyclopropanecarboxylic acids and derivatives / Heteroaromatic compounds / Secondary carboxylic acid amides / Secondary alcohols
show 9 more
Substituents
1,2-diol / Alcohol / Alkyl fluoride / Alkyl halide / Aromatic heteropolycyclic compound / Aryl fluoride / Aryl halide / Azacycle / Benzenoid / Benzodioxole
show 22 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
8RW88Y506K
CAS number
1152311-62-0
InChI Key
MJUVRTYWUMPBTR-MRXNPFEDSA-N
InChI
InChI=1S/C26H27F3N2O6/c1-24(2,13-33)22-8-14-7-18(17(27)10-19(14)31(22)11-16(34)12-32)30-23(35)25(5-6-25)15-3-4-20-21(9-15)37-26(28,29)36-20/h3-4,7-10,16,32-34H,5-6,11-13H2,1-2H3,(H,30,35)/t16-/m1/s1
IUPAC Name
1-(2,2-difluoro-2H-1,3-benzodioxol-5-yl)-N-{1-[(2R)-2,3-dihydroxypropyl]-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl}cyclopropane-1-carboxamide
SMILES
CC(C)(CO)C1=CC2=CC(NC(=O)C3(CC3)C3=CC=C4OC(F)(F)OC4=C3)=C(F)C=C2N1C[C@@H](O)CO

References

General References
  1. Donaldson SH, Pilewski JM, Griese M, Cooke J, Viswanathan L, Tullis E, Davies JC, Lekstrom-Himes JA, Wang LT: Tezacaftor/Ivacaftor in Subjects with Cystic Fibrosis and F508del/F508del-CFTR or F508del/G551D-CFTR. Am J Respir Crit Care Med. 2018 Jan 15;197(2):214-224. doi: 10.1164/rccm.201704-0717OC. [Article]
  2. Taylor-Cousar JL, Munck A, McKone EF, van der Ent CK, Moeller A, Simard C, Wang LT, Ingenito EP, McKee C, Lu Y, Lekstrom-Himes J, Elborn JS: Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del. N Engl J Med. 2017 Nov 23;377(21):2013-2023. doi: 10.1056/NEJMoa1709846. Epub 2017 Nov 3. [Article]
  3. Rowe SM, Daines C, Ringshausen FC, Kerem E, Wilson J, Tullis E, Nair N, Simard C, Han L, Ingenito EP, McKee C, Lekstrom-Himes J, Davies JC: Tezacaftor-Ivacaftor in Residual-Function Heterozygotes with Cystic Fibrosis. N Engl J Med. 2017 Nov 23;377(21):2024-2035. doi: 10.1056/NEJMoa1709847. Epub 2017 Nov 3. [Article]
  4. Garg V, Shen J, Li C, Agarwal S, Gebre A, Robertson S, Huang J, Han L, Jiang L, Stephan K, Wang LT, Lekstrom-Himes J: Pharmacokinetic and Drug-Drug Interaction Profiles of the Combination of Tezacaftor/Ivacaftor. Clin Transl Sci. 2019 May;12(3):267-275. doi: 10.1111/cts.12610. Epub 2019 Jan 29. [Article]
  5. Saint-Criq V, Gray MA: Role of CFTR in epithelial physiology. Cell Mol Life Sci. 2017 Jan;74(1):93-115. doi: 10.1007/s00018-016-2391-y. Epub 2016 Oct 6. [Article]
  6. Kunzelmann K, Mall M: Pharmacotherapy of the ion transport defect in cystic fibrosis: role of purinergic receptor agonists and other potential therapeutics. Am J Respir Med. 2003;2(4):299-309. [Article]
  7. Fraser-Pitt D, O'Neil D: Cystic fibrosis - a multiorgan protein misfolding disease. Future Sci OA. 2015 Sep 1;1(2):FSO57. doi: 10.4155/fso.15.57. eCollection 2015 Sep. [Article]
  8. Fohner AE, McDonagh EM, Clancy JP, Whirl Carrillo M, Altman RB, Klein TE: PharmGKB summary: ivacaftor pathway, pharmacokinetics/pharmacodynamics. Pharmacogenet Genomics. 2017 Jan;27(1):39-42. doi: 10.1097/FPC.0000000000000246. [Article]
  9. Rowe SM, Verkman AS: Cystic fibrosis transmembrane regulator correctors and potentiators. Cold Spring Harb Perspect Med. 2013 Jul 1;3(7). pii: 3/7/a009761. doi: 10.1101/cshperspect.a009761. [Article]
  10. Cystic fibrosis news [Link]
  11. Vertex news [Link]
  12. Vertex news [Link]
  13. Vertex news [Link]
  14. FDA Approved Drug Products: SYMDEKO (tezacaftor/ivacaftor) tablets; (ivacaftor) tablets, for oral use (December 2020) [Link]
  15. FDA Approved Drug Products: Apadaz (benzhydrocodone and acetaminophen) tablets [Link]
  16. NIH Medline Tezacaftor/Ivacaftor [Link]
  17. Pharmacology review, FDA [Link]
  18. Monograph, Tezacaftor/Ivacaftor [Link]
  19. FDA Approved Drug Products: Trikafta (elexacaftor, tezacaftor and ivacaftor tablets; ivacaftor tablets) [Link]
  20. FDA Approved Drug Products: TRIKAFTA® (elexacaftor, tezacaftor, and ivacaftor tablets; ivacaftor tablets), co-packaged for oral use May 2023 [Link]
  21. FDA Approved Drug Products: SYMDEKO™ (tezacaftor/ivacaftor) tablets; (ivacaftor) tablets, for oral use [Link]
Human Metabolome Database
HMDB0304895
KEGG Drug
D11041
PubChem Compound
46199646
PubChem Substance
347828077
ChemSpider
28637762
BindingDB
281054
RxNav
1999382
ChEMBL
CHEMBL3544914
ZINC
ZINC000068206930
PDBe Ligand
CV6
Wikipedia
Tezacaftor
PDB Entries
7sv7 / 8eiq
FDA label
Download (459 KB)
MSDS
Download (27.1 KB)

Clinical Trials

Clinical Trials

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
TabletOral
Tablet, film coatedOral
GranuleOral
Granule; kitOral
Kit; tablet, film coatedOral
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US8324242No2012-12-042027-04-18US flag
US8354427No2013-01-152026-07-06US flag
US8754224No2014-06-172026-12-28US flag
US8410274No2013-04-022026-12-28US flag
US7495103No2009-02-242027-05-20US flag
US8883206No2014-11-112033-02-27US flag
US9670163No2017-06-062026-12-28US flag
US8415387No2013-04-092027-11-12US flag
US9012496No2015-04-212033-07-15US flag
US8598181No2013-12-032027-05-01US flag
US8629162No2014-01-142025-06-24US flag
US8623905No2014-01-072027-05-01US flag
US7645789No2010-01-122027-05-01US flag
US7776905No2010-08-172027-06-03US flag
US9931334No2018-04-032026-12-28US flag
US9974781No2018-05-222027-04-09US flag
US10022352No2018-07-172027-04-09US flag
US10058546No2018-08-282033-07-15US flag
US10081621No2018-09-252031-03-25US flag
US10206877No2019-02-192035-04-14US flag
US10239867No2019-03-262027-04-09US flag
US10272046No2019-04-302033-02-27US flag
US10646481No2020-05-122029-08-13US flag
US10758534No2020-09-012035-10-06US flag
US10793547No2020-10-062037-12-08US flag
US11179367No2021-11-232037-12-08US flag
US11147770No2021-10-192033-02-27US flag
US11426407No2015-10-062035-10-06US flag
US11453655No2017-12-082037-12-08US flag
US11517564No2017-12-082037-12-08US flag
US11564916No2009-08-132029-08-13US flag
US11578062No2011-03-252031-03-25US flag
US11639347No2007-04-092027-04-09US flag
US11752106No2013-02-272033-02-27US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityInsoluble in waterhttps://www.medkoo.com/products/4790
logP99https://www.medkoo.com/uploads/product/Tezacaftor__VX-661_/safety/MSDS-VX661.pdf
pKa13.99, 0.19https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL3544914/
Predicted Properties
PropertyValueSource
Water Solubility0.0124 mg/mLALOGPS
logP2.97ALOGPS
logP4.03Chemaxon
logS-4.6ALOGPS
pKa (Strongest Acidic)11.54Chemaxon
pKa (Strongest Basic)-2.8Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count6Chemaxon
Hydrogen Donor Count4Chemaxon
Polar Surface Area113.18 Å2Chemaxon
Rotatable Bond Count8Chemaxon
Refractivity125.53 m3·mol-1Chemaxon
Polarizability51.79 Å3Chemaxon
Number of Rings5Chemaxon
Bioavailability1Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-00di-0000090000-14f9820a8460b72a4d3b
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0gc0-0000950000-9f87638e7fd15720180c
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-00dj-1500390000-1fe39c99f3fd9a37afff
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-014i-2001930000-124b0f3236966b3ab1e5
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0002-0901540000-de5fd011f1efa4c9d6e4
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-016r-0021910000-0fb484d578d9335debc3
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-221.48015
predicted
DeepCCS 1.0 (2019)
[M+H]+223.87572
predicted
DeepCCS 1.0 (2019)
[M+Na]+229.78825
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Positive allosteric modulator
General Function
Pdz domain binding
Specific Function
Involved in the transport of chloride ions. May regulate bicarbonate secretion and salvage in epithelial cells by regulating the SLC4A7 transporter. Can inhibit the chloride channel activity of ANO...
Gene Name
CFTR
Uniprot ID
P13569
Uniprot Name
Cystic fibrosis transmembrane conductance regulator
Molecular Weight
168139.895 Da
References
  1. Donaldson SH, Pilewski JM, Griese M, Cooke J, Viswanathan L, Tullis E, Davies JC, Lekstrom-Himes JA, Wang LT: Tezacaftor/Ivacaftor in Subjects with Cystic Fibrosis and F508del/F508del-CFTR or F508del/G551D-CFTR. Am J Respir Crit Care Med. 2018 Jan 15;197(2):214-224. doi: 10.1164/rccm.201704-0717OC. [Article]
  2. Taylor-Cousar JL, Munck A, McKone EF, van der Ent CK, Moeller A, Simard C, Wang LT, Ingenito EP, McKee C, Lu Y, Lekstrom-Himes J, Elborn JS: Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del. N Engl J Med. 2017 Nov 23;377(21):2013-2023. doi: 10.1056/NEJMoa1709846. Epub 2017 Nov 3. [Article]
  3. Saint-Criq V, Gray MA: Role of CFTR in epithelial physiology. Cell Mol Life Sci. 2017 Jan;74(1):93-115. doi: 10.1007/s00018-016-2391-y. Epub 2016 Oct 6. [Article]
  4. Cystic fibrosis news [Link]
  5. FDA Approved Drug Products: SYMDEKO (tezacaftor/ivacaftor) tablets; (ivacaftor) tablets, for oral use (December 2020) [Link]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
Inducer
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Garg V, Shen J, Li C, Agarwal S, Gebre A, Robertson S, Huang J, Han L, Jiang L, Stephan K, Wang LT, Lekstrom-Himes J: Pharmacokinetic and Drug-Drug Interaction Profiles of the Combination of Tezacaftor/Ivacaftor. Clin Transl Sci. 2019 May;12(3):267-275. doi: 10.1111/cts.12610. Epub 2019 Jan 29. [Article]
  2. FDA Approved Drug Products: SYMDEKO (tezacaftor/ivacaftor) tablets; (ivacaftor) tablets, for oral use (December 2020) [Link]
  3. Monograph, Tezacaftor/Ivacaftor [Link]
  4. FDA Approved Drug Products: SYMDEKO™ (tezacaftor/ivacaftor) tablets; (ivacaftor) tablets, for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inducer
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Garg V, Shen J, Li C, Agarwal S, Gebre A, Robertson S, Huang J, Han L, Jiang L, Stephan K, Wang LT, Lekstrom-Himes J: Pharmacokinetic and Drug-Drug Interaction Profiles of the Combination of Tezacaftor/Ivacaftor. Clin Transl Sci. 2019 May;12(3):267-275. doi: 10.1111/cts.12610. Epub 2019 Jan 29. [Article]
  2. FDA Approved Drug Products: SYMDEKO (tezacaftor/ivacaftor) tablets; (ivacaftor) tablets, for oral use (December 2020) [Link]
  3. Monograph, Tezacaftor/Ivacaftor [Link]
  4. FDA Approved Drug Products: SYMDEKO™ (tezacaftor/ivacaftor) tablets; (ivacaftor) tablets, for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. FDA Approved Drug Products: Trikafta (elexacaftor, tezacaftor and ivacaftor tablets; ivacaftor tablets) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. FDA Approved Drug Products: Trikafta (elexacaftor, tezacaftor and ivacaftor tablets; ivacaftor tablets) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. FDA Approved Drug Products: Trikafta (elexacaftor, tezacaftor and ivacaftor tablets; ivacaftor tablets) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. FDA Approved Drug Products: Trikafta (elexacaftor, tezacaftor and ivacaftor tablets; ivacaftor tablets) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. FDA Approved Drug Products: Trikafta (elexacaftor, tezacaftor and ivacaftor tablets; ivacaftor tablets) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. FDA Approved Drug Products: Trikafta (elexacaftor, tezacaftor and ivacaftor tablets; ivacaftor tablets) [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Garg V, Shen J, Li C, Agarwal S, Gebre A, Robertson S, Huang J, Han L, Jiang L, Stephan K, Wang LT, Lekstrom-Himes J: Pharmacokinetic and Drug-Drug Interaction Profiles of the Combination of Tezacaftor/Ivacaftor. Clin Transl Sci. 2019 May;12(3):267-275. doi: 10.1111/cts.12610. Epub 2019 Jan 29. [Article]
  2. FDA Approved Drug Products: SYMDEKO (tezacaftor/ivacaftor) tablets; (ivacaftor) tablets, for oral use (December 2020) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
References
  1. FDA Approved Drug Products: Trikafta (elexacaftor, tezacaftor and ivacaftor tablets; ivacaftor tablets) [Link]
  2. FDA Approved Drug Products: SYMDEKO™ (tezacaftor/ivacaftor) tablets; (ivacaftor) tablets, for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Quaternary ammonium group transmembrane transporter activity
Specific Function
Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creat...
Gene Name
SLC22A2
Uniprot ID
O15244
Uniprot Name
Solute carrier family 22 member 2
Molecular Weight
62579.99 Da
References
  1. FDA Approved Drug Products: Trikafta (elexacaftor, tezacaftor and ivacaftor tablets; ivacaftor tablets) [Link]
  2. FDA Approved Drug Products: SYMDEKO™ (tezacaftor/ivacaftor) tablets; (ivacaftor) tablets, for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
Molecular Weight
61815.78 Da
References
  1. FDA Approved Drug Products: Trikafta (elexacaftor, tezacaftor and ivacaftor tablets; ivacaftor tablets) [Link]
  2. FDA Approved Drug Products: SYMDEKO™ (tezacaftor/ivacaftor) tablets; (ivacaftor) tablets, for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenad...
Gene Name
SLC22A8
Uniprot ID
Q8TCC7
Uniprot Name
Solute carrier family 22 member 8
Molecular Weight
59855.585 Da
References
  1. FDA Approved Drug Products: Trikafta (elexacaftor, tezacaftor and ivacaftor tablets; ivacaftor tablets) [Link]
  2. FDA Approved Drug Products: SYMDEKO™ (tezacaftor/ivacaftor) tablets; (ivacaftor) tablets, for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. FDA Approved Drug Products: TRIKAFTA® (elexacaftor, tezacaftor, and ivacaftor tablets; ivacaftor tablets), co-packaged for oral use May 2023 [Link]
  2. FDA Approved Drug Products: SYMDEKO™ (tezacaftor/ivacaftor) tablets; (ivacaftor) tablets, for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 Da
References
  1. FDA Approved Drug Products: SYMDEKO™ (tezacaftor/ivacaftor) tablets; (ivacaftor) tablets, for oral use [Link]

Drug created at October 20, 2016 20:41 / Updated at May 15, 2023 23:19