Identification
- Summary
Ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator used alone or in combination products to treat cystic fibrosis in patients who have specific genetic mutations that are responsive to the medication.
- Brand Names
- Kalydeco, Orkambi, Symdeko, Trikafta (100 Mg / 50 Mg / 75 Mg; 150 Mg)
- Generic Name
- Ivacaftor
- DrugBank Accession Number
- DB08820
- Background
Ivacaftor (also known as Kalydeco or VX-770) is a drug used for the management of Cystic Fibrosis (CF). It is manufactured and distributed by Vertex Pharmaceuticals. It was approved by the Food and Drug Administration on January 31, 201213, and by Health Canada in late 2012.15 Ivacaftor is administered as a monotherapy and also administered in combination with other drugs for the management of CF.14,18,16
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.8
Prior to the development of ivacaftor, management of CF primarily involved therapies for the control of infections, nutritional support, clearance of mucus, and management of symptoms rather than improvements in the underlying disease process or lung function (FEV1). Notably, ivacaftor was the first medication approved for the management of the underlying causes of CF (abnormalities in CFTR protein function) rather than control of symptoms.4
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Ivacaftor (DB08820)
- Weight
- Average: 392.4907
Monoisotopic: 392.209992772 - Chemical Formula
- C24H28N2O3
- Synonyms
- Ivacaftor
- Ivacaftorum
- N-(2,4-di-tert-butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide
- External IDs
- VX 770
- VX-770
- VX770
Pharmacology
- Indication
When used as monotherapy as the product Kalydeco, ivacaftor is indicated for the treatment of cystic fibrosis (CF) in patients aged one month and older who have one mutation in the CFTR gene that is responsive to ivacaftor potentiation based on clinical and/or in vitro assay data.19,25
When used in combination with the drug lumacaftor as the product Orkambi, ivacaftor is indicated for the management of CF in patients aged one year and older who are homozygous for the F508del mutation in the CFTR gene. If the patient’s genotype is unknown, an FDA-cleared CF mutation test should be used to detect the presence of the F508del mutation on both alleles of the CFTR gene.20
When used in combination with tezacaftor in the product Symdeko, it is used to manage CF in patients 12 years and older who have at least one mutation in the CFTR gene or patients aged 12 or older who are shown to be homozygous for the F508del mutation.14
When used in combination with tezacaftor and elexacaftor in the product Trikafta, it is indicated for the treatment of cystic fibrosis in patients 12 years of age and older who have at least one F508del mutation in the CFTR gene.17
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Cystic fibrosis •••••••••••• •••• •••• •••••••• •••••••• •••••• Used in combination to manage Cystic fibrosis Combination Product in combination with: Elexacaftor (DB15444), Tezacaftor (DB11712) •••••••••••• ••••••• Used in combination to manage Cystic fibrosis Combination Product in combination with: Elexacaftor (DB15444), Tezacaftor (DB11712) •••••••••••• •••••• Used in combination to manage Cystic fibrosis Combination Product in combination with: Tezacaftor (DB11712) •••••••••••• •• ••••• ••• •••••••• •• ••• •••••• •••••••• ••••••••••••• ••••••••••• ••••••••• •••••• •••• •••• •• •••••••••• •• •••••••••••••••••••• •••••• Used in combination to manage Cystic fibrosis Combination Product in combination with: Tezacaftor (DB11712) •••••••••••• •••••••••• ••• ••••••• •••••••• •• ••• •••• •••• •••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
The use of Ivacaftor has been shown to both improve CF symptoms and modulate underlying disease pathology. This is achieved by potentiating the channel opening probability (or gating) of CFTR protein in patients with impaired gating mechanisms. This is in contrast to Lumacaftor, another CF medication, that functions by preventing misfolding of the CFTR protein and thereby results in increased processing and trafficking of mature protein to the cell surface.
Results from clinical trials indicated that treatment with ivacaftor results in improved lung function, reduced chance of experiencing a pulmonary exacerbation, reduced sweat chloride, increased weight gain, and improvements in CF symptoms and quality of life.18 When combined with tezacaftor, significant improvements in lung function have been observed in clinical studies.14 Ivacaftor was not found to increase the QTc interval in a clinically significant manner.18
Although ivacaftor given alone has not shown any significant improvements in patients with the delta-F508 mutation, it has shown significant improvements (>10% increase in FEV1 from baseline) in lung function for the following mutations: E56K, P67L, R74W, D110E, D110H, R117C, R117H, G178R, E193K, L206W, R347H, R352Q, A455E, S549N, S549R, G551D, G551S, D579G, S945L, S977F, F1052V, K1060T, A1067T, G1069R, R1070Q, R1070W, F1074L, D1152H, G1244E, S1251N, S1255P, D1270N, and G1349.18 This list was expanded by the FDA in May 2017 from 10 to 33 to accommodate more rare mutations.13
It is important to note that this drug may cause an increase in liver transaminases (ALT, AST). Ensure to assess liver transaminases before the initiation of treatment, every 3 months during the first year of administration, followed by every year thereafter.18
- Mechanism of action
A wide variety of CFTR mutations correlate to the Cystic Fibrosis phenotype and are associated with differing levels of disease severity. The most common mutation, affecting approximately 70% of patients with CF worldwide, is known as F508del-CFTR or delta-F508 (ΔF508), in which a deletion in the amino acid phenylalanine at position 508 results in impaired production of the CFTR protein, thereby causing a significant reduction in the amount of ion transporter present on cell membranes.7 Ivacaftor as monotherapy has failed to show a benefit for patients with delta-F508 mutations, most likely due to an insufficient amount of protein available at the cell membrane for interaction and potentiation by the drug.10 The next most common mutation, G551D, affecting 4-5% of CF patients worldwide is characterized as a missense mutation, whereby there is sufficient amount of protein at the cell surface, but opening and closing mechanisms of the channel are altered.9 Ivacaftor is indicated for the management of CF in patients with this second type of mutation, as it binds to and potentiates the channel opening ability of CFTR proteins on the cell membrane.9
Ivacaftor exerts its effect by acting as a potentiator of the CFTR protein, an ion channel involved in the transport of chloride and sodium ions across cell membranes of the lungs, pancreas, and other organs. 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. Ivacaftor improves CF symptoms and underlying disease pathology by potentiating the channel open probability (or gating) of CFTR protein in patients with impaired CFTR gating mechanisms. The overall level of ivacaftor-mediated CFTR chloride transport is dependent on the amount of CFTR protein at the cell surface and how responsive a particular mutant CFTR protein is to ivacaftor potentiation 18.
Target Actions Organism ACystic fibrosis transmembrane conductance regulator potentiatorHumans - Absorption
Ivacaftor is well absorbed in the gastrointestinal tract.12 Following administration of ivacaftor with fat-containing foods, peak plasma concentrations were reached at 4 hours (Tmax) with a maximum concentration (Cmax) of 768 ng/mL and AUC of 10600 ng * hr/mL. It is recommended that ivacaftor is taken with fat-containing foods as they increase absorption by approximately 2.5- to 4-fold.18
- Volume of distribution
After oral administration of 150 mg every 12 hours for 7 days to healthy volunteers in a fed state, the mean (±SD) for apparent volume of distribution was 353 (122) L.18
- Protein binding
About 99% of ivacaftor is bound to plasma proteins, primarily to alpha 1-acid glycoprotein and albumin.12,14
- Metabolism
Ivacaftor is extensively metabolized in humans. In vitro and clinical studies indicate that ivacaftor is primarily metabolized by CYP3A. From this metabolism, the major formed metabolites are M1 and M6. M1 is considered pharmacologically active even though it just presents approximately one-sixth the effect of the parent compound ivacaftor. On the other hand, M6 is not considered pharmacologically active as it represents less than one-fiftieth of the effect of the parent compound.12,18
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- Route of elimination
After oral administration, ivacaftor is mainly eliminated in the feces after metabolic conversion and this elimination represents 87.8% of the dose. From the total eliminated dose, the metabolites M1 and M6 account for the majority of the eliminated dose, being 22% for M1 and 43% for M6. Ivacaftor shows negligible urinary excretion as the unchanged drug.12,18
- Half-life
In a clinical study, the apparent terminal half-life was approximately 12 hours following a single dose of ivacaftor.18 One source mentions the half-life ranges from 12 to 14 hours.12
- Clearance
The CL/F (SD) for the 150 mg dose was 17.3 (8.4) L/hr in healthy subjects.18
- Adverse Effects
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LD50 information is not readily available. There have been no reports of overdose with ivacaftor, but when given with tezacaftor, the highest clinical dose lead to diarrhea and dizziness. Provide supportive measures in cases of a suspected overdose. No antidote is available at this time.14
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Interacting Gene/Enzyme Allele name Genotype(s) Defining Change(s) Type(s) Description Details Cystic fibrosis transmembrane conductance regulator --- (A;A) / (A;G) A allele (G > A), double homozygote Effect Directly Studied Patients who carry this polymorphism in CFTR will respond to ivacaftor therapy. Details
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The serum concentration of 1,2-Benzodiazepine can be increased when it is combined with Ivacaftor. Abametapir The serum concentration of Ivacaftor can be increased when it is combined with Abametapir. Abatacept The metabolism of Ivacaftor can be increased when combined with Abatacept. Abemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Ivacaftor. Abiraterone The serum concentration of Abiraterone can be increased when it is combined with Ivacaftor. - Food Interactions
- Take with a high fat meal. Co-administration with a high fat meal increases exposure to ivacaftor.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Kalydeco Tablet, film coated 150 mg/1 Oral Vertex Pharmaceuticals Incorporated 2012-01-31 Not applicable US 
Kalydeco Tablet, film coated 150 mg Oral Vertex Pharmaceuticals (Ireland) Limited 2020-12-15 Not applicable EU 
Kalydeco Granule 13.4 mg/1 Oral Vertex Pharmaceuticals Incorporated 2023-05-03 Not applicable US Kalydeco Granule 50 mg / sachet Oral Vertex Pharmaceuticals Incorporated 2015-09-14 Not applicable Canada 
Kalydeco Granule 75 mg/1 Oral Vertex Pharmaceuticals Incorporated 2015-03-23 Not applicable US - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Kaftrio Ivacaftor (75 mg) + Elexacaftor (100 mg) + Tezacaftor (50 mg) Tablet, film coated Oral Vertex Pharmaceuticals (Ireland) Limited 2020-12-15 Not applicable EU KAFTRIO Ivacaftor (75 MG) + Elexacaftor (100 MG) + Tezacaftor (50 MG) Tablet, film coated Oral Vertex Pharmaceuticals (Ireland) Limited 2020-11-14 Not applicable Italy 
Kaftrio Ivacaftor (37.5 mg) + Elexacaftor (50 mg) + Tezacaftor (25 mg) Tablet, film coated Oral Vertex Pharmaceuticals (Ireland) Limited 2022-05-04 Not applicable EU Orkambi Ivacaftor (188 mg) + Lumacaftor (150 mg) Granule Oral Vertex Pharmaceuticals (Ireland) Limited 2020-12-22 Not applicable EU Orkambi Ivacaftor (125 mg) + Lumacaftor (200 mg) Tablet, film coated Oral Vertex Pharmaceuticals (Ireland) Limited 2016-09-08 2021-11-12 EU
Categories
- ATC Codes
- R07AX32 — Ivacaftor, tezacaftor and elexacaftor
- R07AX — Other respiratory system products
- R07A — OTHER RESPIRATORY SYSTEM PRODUCTS
- R07 — OTHER RESPIRATORY SYSTEM PRODUCTS
- R — RESPIRATORY SYSTEM
- R07AX — Other respiratory system products
- R07A — OTHER RESPIRATORY SYSTEM PRODUCTS
- R07 — OTHER RESPIRATORY SYSTEM PRODUCTS
- R — RESPIRATORY SYSTEM
- R07AX — Other respiratory system products
- R07A — OTHER RESPIRATORY SYSTEM PRODUCTS
- R07 — OTHER RESPIRATORY SYSTEM PRODUCTS
- R — RESPIRATORY SYSTEM
- Drug Categories
- Amines
- Aniline Compounds
- Benzene Derivatives
- Chloride Channel Activation Potentiators
- Chloride Channel Agonists
- Cystic Fibrosis Transmembrane Conductance Regulator Potentiators
- Cytochrome P-450 CYP2C9 Inhibitors
- Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (weak)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A5 Inhibitors
- Cytochrome P-450 CYP3A5 Inhibitors (weak)
- Cytochrome P-450 CYP3A5 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Heterocyclic Compounds, Fused-Ring
- Membrane Transport Modulators
- P-glycoprotein inhibitors
- Phenols
- Quinolines
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as aromatic anilides. These are aromatic compounds containing an anilide group in which the carboxamide group is substituted with an aromatic group. They have the general structure RNC(=O)R', where R= benzene, and R = aryl group.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Anilides
- Direct Parent
- Aromatic anilides
- Alternative Parents
- Quinoline-3-carboxamides / Hydroquinolones / Hydroquinolines / Pyridinecarboxylic acids and derivatives / Phenylpropanes / 1-hydroxy-2-unsubstituted benzenoids / Vinylogous amides / Heteroaromatic compounds / Secondary carboxylic acid amides / Azacyclic compounds show 5 more
- Substituents
- 1-hydroxy-2-unsubstituted benzenoid / Aromatic anilide / Aromatic heteropolycyclic compound / Azacycle / Carboxamide group / Carboxylic acid derivative / Dihydroquinoline / Dihydroquinolone / Heteroaromatic compound / Hydrocarbon derivative show 15 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- monocarboxylic acid amide, phenols, aromatic amide, quinolone (CHEBI:66901)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 1Y740ILL1Z
- CAS number
- 873054-44-5
- InChI Key
- PURKAOJPTOLRMP-UHFFFAOYSA-N
- InChI
- InChI=1S/C24H28N2O3/c1-23(2,3)16-11-17(24(4,5)6)20(27)12-19(16)26-22(29)15-13-25-18-10-8-7-9-14(18)21(15)28/h7-13,27H,1-6H3,(H,25,28)(H,26,29)
- IUPAC Name
- N-(2,4-di-tert-butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide
- SMILES
- CC(C)(C)C1=CC(=C(O)C=C1NC(=O)C1=CNC2=CC=CC=C2C1=O)C(C)(C)C
References
- General References
- Accurso FJ, Rowe SM, Clancy JP, Boyle MP, Dunitz JM, Durie PR, Sagel SD, Hornick DB, Konstan MW, Donaldson SH, Moss RB, Pilewski JM, Rubenstein RC, Uluer AZ, Aitken ML, Freedman SD, Rose LM, Mayer-Hamblett N, Dong Q, Zha J, Stone AJ, Olson ER, Ordonez CL, Campbell PW, Ashlock MA, Ramsey BW: Effect of VX-770 in persons with cystic fibrosis and the G551D-CFTR mutation. N Engl J Med. 2010 Nov 18;363(21):1991-2003. doi: 10.1056/NEJMoa0909825. [Article]
- Ramsey BW, Davies J, McElvaney NG, Tullis E, Bell SC, Drevinek P, Griese M, McKone EF, Wainwright CE, Konstan MW, Moss R, Ratjen F, Sermet-Gaudelus I, Rowe SM, Dong Q, Rodriguez S, Yen K, Ordonez C, Elborn JS: A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med. 2011 Nov 3;365(18):1663-72. doi: 10.1056/NEJMoa1105185. [Article]
- Eckford PD, Li C, Ramjeesingh M, Bear CE: Cystic fibrosis transmembrane conductance regulator (CFTR) potentiator VX-770 (ivacaftor) opens the defective channel gate of mutant CFTR in a phosphorylation-dependent but ATP-independent manner. J Biol Chem. 2012 Oct 26;287(44):36639-49. doi: 10.1074/jbc.M112.393637. Epub 2012 Aug 31. [Article]
- Van Goor F, Hadida S, Grootenhuis PD, Burton B, Cao D, Neuberger T, Turnbull A, Singh A, Joubran J, Hazlewood A, Zhou J, McCartney J, Arumugam V, Decker C, Yang J, Young C, Olson ER, Wine JJ, Frizzell RA, Ashlock M, Negulescu P: Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770. Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18825-30. doi: 10.1073/pnas.0904709106. Epub 2009 Oct 21. [Article]
- 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]
- 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]
- MacDonald KD, McKenzie KR, Zeitlin PL: Cystic fibrosis transmembrane regulator protein mutations: 'class' opportunity for novel drug innovation. Paediatr Drugs. 2007;9(1):1-10. [Article]
- 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]
- Yu H, Burton B, Huang CJ, Worley J, Cao D, Johnson JP Jr, Urrutia A, Joubran J, Seepersaud S, Sussky K, Hoffman BJ, Van Goor F: Ivacaftor potentiation of multiple CFTR channels with gating mutations. J Cyst Fibros. 2012 May;11(3):237-45. doi: 10.1016/j.jcf.2011.12.005. Epub 2012 Jan 30. [Article]
- Flume PA, Liou TG, Borowitz DS, Li H, Yen K, Ordonez CL, Geller DE: Ivacaftor in subjects with cystic fibrosis who are homozygous for the F508del-CFTR mutation. Chest. 2012 Sep;142(3):718-724. doi: 10.1378/chest.11-2672. [Article]
- Mayer M: Lumacaftor-ivacaftor (Orkambi) for cystic fibrosis: behind the 'breakthrough'. Evid Based Med. 2016 Jun;21(3):83-6. doi: 10.1136/ebmed-2015-110325. Epub 2015 Dec 30. [Article]
- 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]
- FDA Approval Update May 17, 2017 [Link]
- FDA Approved Drug Products: SYMDEKO (tezacaftor/ivacaftor) tablets; (ivacaftor) tablets, for oral use (December 2020) [Link]
- Cystic Fibrosis, Canada [Link]
- FDA Approved Drug Products: ORKAMBI (lumacaftor/ivacaftor) granules or tablets, for oral use [Link]
- FDA Approved Drug Products: Trikafta (elexacaftor, tezacaftor and ivacaftor tablets; ivacaftor tablets) [Link]
- FDA Approved Drug Products: Kalydeco (ivacaftor) tablets or granules, for oral use [Link]
- Health Canada Product Monograph: KALYDECO (ivacaftor) Oral Tablets or Granules [Link]
- FDA Approved Drug Products: ORKAMBI (lumacaftor and ivacaftor) tablets or granules, for oral use (September 2022) [Link]
- Health Canada Approved Drug Producs: ORKAMBI (Lumacaftor / Ivacaftor) tablets for oral use [Link]
- Dailymed: TRIKAFTA (elexacaftor, tezacaftor, and ivacaftor kit) tablets, for oral use [Link]
- FDA Approved Drug Products: SYMDEKO™ (tezacaftor/ivacaftor) tablets; (ivacaftor) tablets, for oral use [Link]
- FDA Approved Drug Products: TRIKAFTA® (elexacaftor, tezacaftor, and ivacaftor tablets; ivacaftor tablets), co-packaged for oral use May 2023 [Link]
- FDA Approved Drug Products: KALYDECO (ivacaftor) tablets or granules, for oral use (May 2023) [Link]
- Health Canada Product Monograph: KALYDECO (ivacaftor) Oral Tablets or Granules (Dec 2023) [Link]
- External Links
- Human Metabolome Database
- HMDB0015705
- KEGG Drug
- D09916
- PubChem Compound
- 16220172
- PubChem Substance
- 175427103
- ChemSpider
- 17347474
- BindingDB
- 50032693
- 1243041
- ChEBI
- 66901
- ChEMBL
- CHEMBL2010601
- ZINC
- ZINC000052509463
- PharmGKB
- PA165950341
- PDBe Ligand
- VX7
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Ivacaftor
- PDB Entries
- 6o2p / 7otg / 8eiq
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Active Not Recruiting Other Adherence, Medication / Cystic Fibrosis (CF) / Cystic Fibrosis Gastrointestinal Disease / Cystic Fibrosis in Children / Cystic Fibrosis Liver Disease 1 4 Completed Other Cystic Fibrosis (CF) 1 4 Completed Treatment Cystic Fibrosis (CF) 2 4 Recruiting Other Drug Drug Interaction (DDI) 1 4 Recruiting Treatment Cystic Fibrosis (CF) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Granule Oral 13.4 mg/1 Granule Oral 13.4 mg / sachet Granule Oral 25 MG Granule Oral 25 mg/1 Granule Oral 25 mg / sachet Granule Oral 5.8 mg/1 Granule Oral 50 mg / sachet Granule Oral 50 mg/1 Granule Oral 50 MG Granule Oral 75 mg/1 Granule Oral 75 MG Granule Oral 75 mg / sachet Tablet Oral 150 mg Tablet, film coated Oral 150 MG Tablet, film coated Oral 150 mg/1 Tablet, film coated Oral 75 MG Granule Oral Tablet Oral Tablet, film coated Oral Granule; kit Oral Kit; tablet, film coated Oral - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8324242 No 2012-12-04 2027-04-18 US US8354427 No 2013-01-15 2026-07-06 US US8754224 No 2014-06-17 2026-12-28 US US8410274 No 2013-04-02 2026-12-28 US US7495103 No 2009-02-24 2027-05-20 US US8741933 No 2014-06-03 2026-11-08 US US8716338 No 2014-05-06 2026-11-08 US US8846718 No 2014-09-30 2028-12-04 US US8653103 No 2014-02-18 2028-12-04 US US9216969 No 2015-12-22 2026-11-08 US US8507534 No 2013-08-13 2030-09-20 US US8993600 No 2015-03-31 2030-12-11 US US8883206 No 2014-11-11 2033-02-27 US US9670163 No 2017-06-06 2026-12-28 US US9192606 No 2015-11-24 2029-09-29 US US7973038 No 2011-07-05 2026-11-08 US US9150552 No 2015-10-06 2028-12-04 US US8415387 No 2013-04-09 2027-11-12 US US9012496 No 2015-04-21 2033-07-15 US US8598181 No 2013-12-03 2027-05-01 US US8629162 No 2014-01-14 2025-06-24 US US8623905 No 2014-01-07 2027-05-01 US US7645789 No 2010-01-12 2027-05-01 US US7776905 No 2010-08-17 2027-06-03 US US9931334 No 2018-04-03 2026-12-28 US US9974781 No 2018-05-22 2027-04-09 US US10022352 No 2018-07-17 2027-04-09 US US10058546 No 2018-08-28 2033-07-15 US US10081621 No 2018-09-25 2031-03-25 US US10076513 No 2018-09-18 2028-12-04 US US10206877 No 2019-02-19 2035-04-14 US US10239867 No 2019-03-26 2027-04-09 US US10272046 No 2019-04-30 2033-02-27 US US10597384 No 2020-03-24 2028-12-04 US US10646481 No 2020-05-12 2029-08-13 US US10758534 No 2020-09-01 2035-10-06 US US10793547 No 2020-10-06 2037-12-08 US US11052075 No 2021-07-06 2028-12-04 US US11179367 No 2021-11-23 2037-12-08 US US11147770 No 2021-10-19 2033-02-27 US US11426407 No 2015-10-06 2035-10-06 US US11453655 No 2017-12-08 2037-12-08 US US11517564 No 2017-12-08 2037-12-08 US US11564916 No 2009-08-13 2029-08-13 US US11578062 No 2011-03-25 2031-03-25 US US11639347 No 2007-04-09 2027-04-09 US US11752106 No 2013-02-27 2033-02-27 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 212-215 https://www.trc-canada.com/product-detail/?I940600 boiling point (°C) 550.4 https://www.lookchem.com/Ivacaftor/ water solubility low (<0.05 µg/mL) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5140711/ logP 3.13 https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL2010601/ pKa 11.08, 1.5 https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL2010601/ - Predicted Properties
Property Value Source Water Solubility 0.002 mg/mL ALOGPS logP 5 ALOGPS logP 5.76 Chemaxon logS -5.3 ALOGPS pKa (Strongest Acidic) 9.66 Chemaxon pKa (Strongest Basic) -0.95 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 78.43 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 118.68 m3·mol-1 Chemaxon Polarizability 44.39 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9577 Blood Brain Barrier + 0.6561 Caco-2 permeable - 0.5608 P-glycoprotein substrate Non-substrate 0.5474 P-glycoprotein inhibitor I Non-inhibitor 0.7677 P-glycoprotein inhibitor II Non-inhibitor 0.7609 Renal organic cation transporter Non-inhibitor 0.945 CYP450 2C9 substrate Non-substrate 0.7374 CYP450 2D6 substrate Non-substrate 0.8362 CYP450 3A4 substrate Substrate 0.5686 CYP450 1A2 substrate Inhibitor 0.5438 CYP450 2C9 inhibitor Inhibitor 0.6456 CYP450 2D6 inhibitor Non-inhibitor 0.9469 CYP450 2C19 inhibitor Non-inhibitor 0.6422 CYP450 3A4 inhibitor Non-inhibitor 0.8404 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.5791 Ames test Non AMES toxic 0.8394 Carcinogenicity Non-carcinogens 0.8149 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.2868 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9961 hERG inhibition (predictor II) Non-inhibitor 0.819
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 204.5735722 predictedDarkChem Lite v0.1.0 [M-H]- 205.4664722 predictedDarkChem Lite v0.1.0 [M-H]- 200.78508 predictedDeepCCS 1.0 (2019) [M+H]+ 205.4893722 predictedDarkChem Lite v0.1.0 [M+H]+ 206.3758722 predictedDarkChem Lite v0.1.0 [M+H]+ 203.14308 predictedDeepCCS 1.0 (2019) [M+Na]+ 205.4476722 predictedDarkChem Lite v0.1.0 [M+Na]+ 205.6909722 predictedDarkChem Lite v0.1.0 [M+Na]+ 209.92986 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Potentiator
- 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
- Yu H, Burton B, Huang CJ, Worley J, Cao D, Johnson JP Jr, Urrutia A, Joubran J, Seepersaud S, Sussky K, Hoffman BJ, Van Goor F: Ivacaftor potentiation of multiple CFTR channels with gating mutations. J Cyst Fibros. 2012 May;11(3):237-45. doi: 10.1016/j.jcf.2011.12.005. Epub 2012 Jan 30. [Article]
- 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]
- FDA Approved Drug Products: Kalydeco (ivacaftor) tablets or granules, for oral use [Link]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- SubstrateInhibitor
- 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
- Robertson SM, Luo X, Dubey N, Li C, Chavan AB, Gilmartin GS, Higgins M, Mahnke L: Clinical drug-drug interaction assessment of ivacaftor as a potential inhibitor of cytochrome P450 and P-glycoprotein. J Clin Pharmacol. 2015 Jan;55(1):56-62. doi: 10.1002/jcph.377. Epub 2014 Aug 27. [Article]
- Guimbellot JS, Acosta EP, Rowe SM: Sensitivity of ivacaftor to drug-drug interactions with rifampin, a cytochrome P450 3A4 inducer. Pediatr Pulmonol. 2018 May;53(5):E6-E8. doi: 10.1002/ppul.23971. Epub 2018 Feb 28. [Article]
- FDA Approved Drug Products: Kalydeco (ivacaftor) tablets or granules, for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- SubstrateInhibitor
- 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
- Robertson SM, Luo X, Dubey N, Li C, Chavan AB, Gilmartin GS, Higgins M, Mahnke L: Clinical drug-drug interaction assessment of ivacaftor as a potential inhibitor of cytochrome P450 and P-glycoprotein. J Clin Pharmacol. 2015 Jan;55(1):56-62. doi: 10.1002/jcph.377. Epub 2014 Aug 27. [Article]
- Guimbellot JS, Acosta EP, Rowe SM: Sensitivity of ivacaftor to drug-drug interactions with rifampin, a cytochrome P450 3A4 inducer. Pediatr Pulmonol. 2018 May;53(5):E6-E8. doi: 10.1002/ppul.23971. Epub 2018 Feb 28. [Article]
- FDA Approved Drug Products: Kalydeco (ivacaftor) tablets or granules, for oral use [Link]
- FDA Approved Drug Products: ORKAMBI (lumacaftor/ivacaftor) granules or tablets, for oral use [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
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- Kapoor H, Koolwal A, Singh A: Ivacaftor: a novel mutation modulating drug. J Clin Diagn Res. 2014 Nov;8(11):SE01-5. doi: 10.7860/JCDR/2014/6486.5158. Epub 2014 Nov 20. [Article]
- FDA Approved Drug Products: Kalydeco (ivacaftor) tablets or granules, for oral use [Link]
- FDA Approved Drug Products: ORKAMBI (lumacaftor/ivacaftor) granules or tablets, for oral use [Link]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Carrier
- General Function
- Toxic substance binding
- Specific Function
- Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Serum albumin
- Molecular Weight
- 69365.94 Da
References
- Schneider EK, Huang JX, Carbone V, Baker M, Azad MA, Cooper MA, Li J, Velkov T: Drug-drug plasma protein binding interactions of ivacaftor. J Mol Recognit. 2015 Jun;28(6):339-48. doi: 10.1002/jmr.2447. Epub 2015 Feb 24. [Article]
- FDA Approved Drug Products: SYMDEKO (tezacaftor/ivacaftor) tablets; (ivacaftor) tablets, for oral use (December 2020) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Carrier
- General Function
- Not Available
- Specific Function
- Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
- Gene Name
- ORM1
- Uniprot ID
- P02763
- Uniprot Name
- Alpha-1-acid glycoprotein 1
- Molecular Weight
- 23511.38 Da
References
- Schneider EK, Huang JX, Carbone V, Baker M, Azad MA, Cooper MA, Li J, Velkov T: Drug-drug plasma protein binding interactions of ivacaftor. J Mol Recognit. 2015 Jun;28(6):339-48. doi: 10.1002/jmr.2447. Epub 2015 Feb 24. [Article]
- FDA Approved Drug Products: SYMDEKO (tezacaftor/ivacaftor) tablets; (ivacaftor) tablets, for oral use (December 2020) [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- 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
- Robertson SM, Luo X, Dubey N, Li C, Chavan AB, Gilmartin GS, Higgins M, Mahnke L: Clinical drug-drug interaction assessment of ivacaftor as a potential inhibitor of cytochrome P450 and P-glycoprotein. J Clin Pharmacol. 2015 Jan;55(1):56-62. doi: 10.1002/jcph.377. Epub 2014 Aug 27. [Article]
- McColley SA: A safety evaluation of ivacaftor for the treatment of cystic fibrosis. Expert Opin Drug Saf. 2016 May;15(5):709-15. doi: 10.1517/14740338.2016.1165666. Epub 2016 Apr 7. [Article]
- FDA Approved Drug Products: KALYDECO (ivacaftor) tablets or granules, for oral use (May 2023) [Link]
Drug created at February 24, 2012 18:15 / Updated at December 12, 2023 05:06