Details of the Drug

General Information of Drug (ID: DMHZCPO)

Drug Name
Ibrutinib
Synonyms PCI-32765; Ibrutinib (BTK inhibitor)
Indication
Disease Entry ICD 11 Status REF
Mantle cell lymphoma 2A85.5 Approved [1], [2], [3]
B-cell non-hodgkin lymphoma 2B33.5 Phase 3 [4]
Diffuse large B-cell lymphoma 2A81 Phase 3 [4]
Follicular lymphoma 2A80 Phase 3 [4]
Non-hodgkin lymphoma 2B33.5 Phase 3 [4]
Pancreatic cancer 2C10 Phase 3 [4]
Solid tumour/cancer 2A00-2F9Z Phase 2 [4]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 440.5
Topological Polar Surface Area (xlogp) 3.6
Rotatable Bond Count (rotbonds) 5
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 6
ADMET Property
Clearance
The drug present in the plasma can be removed from the body at the rate of 16.4 mL/min/kg [5]
Half-life
The concentration or amount of drug in body reduced by one-half in 5 hours [5]
Unbound Fraction
The unbound fraction of drug in plasma is 0.03% [5]
Vd
Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 9.75 L/kg [5]
Chemical Identifiers
Formula
C25H24N6O2
IUPAC Name
1-[(3R)-3-[4-amino-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]prop-2-en-1-one
Canonical SMILES
C=CC(=O)N1CCC[C@H](C1)N2C3=NC=NC(=C3C(=N2)C4=CC=C(C=C4)OC5=CC=CC=C5)N
InChI
InChI=1S/C25H24N6O2/c1-2-21(32)30-14-6-7-18(15-30)31-25-22(24(26)27-16-28-25)23(29-31)17-10-12-20(13-11-17)33-19-8-4-3-5-9-19/h2-5,8-13,16,18H,1,6-7,14-15H2,(H2,26,27,28)/t18-/m1/s1
InChIKey
XYFPWWZEPKGCCK-GOSISDBHSA-N
Cross-matching ID
PubChem CID
24821094
ChEBI ID
CHEBI:76612
CAS Number
936563-96-1
DrugBank ID
DB09053
TTD ID
D09KTS
VARIDT ID
DR01270
INTEDE ID
DR0843
ACDINA ID
D01146

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Tyrosine-protein kinase BTK (ATK) TTGM6VW BTK_HUMAN Inhibitor [6]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [7]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [8]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Substrate [8]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Substrate [8]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Mantle cell lymphoma
ICD Disease Classification 2A85.5
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Tyrosine-protein kinase BTK (ATK) DTT BTK 3.54E-01 0.24 0.56
P-glycoprotein 1 (ABCB1) DTP P-GP 7.45E-02 -1.49E-01 -3.47E-01
Cytochrome P450 3A5 (CYP3A5) DME CYP3A5 1.34E-01 -2.79E-01 -7.05E-01
Cytochrome P450 2D6 (CYP2D6) DME CYP2D6 1.61E-03 -6.79E-01 -2.18E+00
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 9.81E-01 2.72E-01 6.95E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Ibrutinib
DDI Drug Name DDI Drug ID Severity Mechanism Disease REF
Acalabrutinib DM7GCVW Major Increased risk of bleeding by the combination of Ibrutinib and Acalabrutinib. Mature B-cell lymphoma [2A85] [49]
Coadministration of a Drug Treating the Disease Different from Ibrutinib (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Ivosidenib DM8S6T7 Moderate Increased metabolism of Ibrutinib caused by Ivosidenib mediated induction of CYP450 enzyme. Acute myeloid leukaemia [2A60] [50]
Arn-509 DMT81LZ Major Increased metabolism of Ibrutinib caused by Arn-509 mediated induction of CYP450 enzyme. Acute myeloid leukaemia [2A60] [51]
Gilteritinib DMWQ4MZ Moderate Decreased clearance of Ibrutinib due to the transporter inhibition by Gilteritinib. Acute myeloid leukaemia [2A60] [51]
Pexidartinib DMS2J0Z Moderate Increased metabolism of Ibrutinib caused by Pexidartinib mediated induction of CYP450 enzyme. Bone/articular cartilage neoplasm [2F7B] [50]
Talazoparib DM1KS78 Moderate Decreased clearance of Ibrutinib due to the transporter inhibition by Talazoparib. Breast cancer [2C60-2C6Y] [52]
Tucatinib DMBESUA Major Decreased metabolism of Ibrutinib caused by Tucatinib mediated inhibition of CYP450 enzyme. Breast cancer [2C60-2C6Y] [53]
Lumacaftor DMCLWDJ Major Increased metabolism of Ibrutinib caused by Lumacaftor mediated induction of CYP450 enzyme. Cystic fibrosis [CA25] [51]
Vortioxetine DM6F1PU Moderate Increased risk of bleeding by the combination of Ibrutinib and Vortioxetine. Depression [6A70-6A7Z] [54]
Tazemetostat DMWP1BH Major Increased risk of bleeding by the combination of Ibrutinib and Tazemetostat. Follicular lymphoma [2A80] [55]
Ripretinib DM958QB Moderate Decreased clearance of Ibrutinib due to the transporter inhibition by Ripretinib. Gastrointestinal stromal tumour [2B5B] [53]
Avapritinib DMK2GZX Major Increased risk of bleeding by the combination of Ibrutinib and Avapritinib. Gastrointestinal stromal tumour [2B5B] [51]
Cobicistat DM6L4H2 Major Decreased metabolism of Ibrutinib caused by Cobicistat mediated inhibition of CYP450 enzyme. Human immunodeficiency virus disease [1C60-1C62] [53]
Epanova DMHEAGL Major Increased risk of bleeding by the combination of Ibrutinib and Epanova. Hyper-lipoproteinaemia [5C80] [56]
Ceritinib DMB920Z Major Decreased metabolism of Ibrutinib caused by Ceritinib mediated inhibition of CYP450 enzyme. Lung cancer [2C25] [53]
PF-06463922 DMKM7EW Moderate Increased metabolism of Ibrutinib caused by PF-06463922 mediated induction of CYP450 enzyme. Lung cancer [2C25] [50]
Idelalisib DM602WT Major Decreased metabolism of Ibrutinib caused by Idelalisib mediated inhibition of CYP450 enzyme. Mature B-cell leukaemia [2A82] [53]
GDC-0199 DMH0QKA Major Decreased clearance of Ibrutinib due to the transporter inhibition by GDC-0199. Mature B-cell leukaemia [2A82] [53]
Arry-162 DM1P6FR Major Increased risk of bleeding by the combination of Ibrutinib and Arry-162. Melanoma [2C30] [55]
LGX818 DMNQXV8 Major Increased risk of bleeding by the combination of Ibrutinib and LGX818. Melanoma [2C30] [55]
Ubrogepant DM749I3 Moderate Decreased clearance of Ibrutinib due to the transporter inhibition by Ubrogepant. Migraine [8A80] [57]
Rimegepant DMHOAUG Moderate Decreased clearance of Ibrutinib due to the transporter inhibition by Rimegepant. Migraine [8A80] [58]
Siponimod DM2R86O Major Additive immunosuppressive effects by the combination of Ibrutinib and Siponimod. Multiple sclerosis [8A40] [53]
Ocrelizumab DMEZ2KH Moderate Additive immunosuppressive effects by the combination of Ibrutinib and Ocrelizumab. Multiple sclerosis [8A40] [59]
Fedratinib DM4ZBK6 Major Increased risk of bleeding by the combination of Ibrutinib and Fedratinib. Myeloproliferative neoplasm [2A20] [50]
Lefamulin DME6G97 Moderate Decreased clearance of Ibrutinib due to the transporter inhibition by Lefamulin. Pneumonia [CA40] [60]
Relugolix DMK7IWL Moderate Decreased clearance of Ibrutinib due to the transporter inhibition by Relugolix. Prostate cancer [2C82] [51]
Anthrax vaccine DM9GSWY Moderate Antagonize the effect of Ibrutinib when combined with Anthrax vaccine. Sepsis [1G40-1G41] [61]
Voxelotor DMCS6M5 Moderate Decreased metabolism of Ibrutinib caused by Voxelotor mediated inhibition of CYP450 enzyme. Sickle-cell disorder [3A51] [50]
Larotrectinib DM26CQR Moderate Decreased clearance of Ibrutinib due to the transporter inhibition by Larotrectinib. Solid tumour/cancer [2A00-2F9Z] [50]
Lusutrombopag DMH6IKO Moderate Decreased clearance of Ibrutinib due to the transporter inhibition by Lusutrombopag. Thrombocytopenia [3B64] [62]
Elagolix DMB2C0E Moderate Increased metabolism of Ibrutinib caused by Elagolix mediated induction of CYP450 enzyme. Uterine fibroid [2E86] [50]
Betrixaban DM2C4RF Major Increased risk of bleeding by the combination of Ibrutinib and Betrixaban. Venous thromboembolism [BD72] [55]
⏷ Show the Full List of 32 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG
DIG Name DIG ID PubChem CID Functional Classification
Sodium lauryl sulfate E00464 3423265 Emulsifying agent; Modified-release agent; Penetration agent; Solubilizing agent; Surfactant; lubricant
Carmellose sodium E00625 Not Available Disintegrant
Ferrosoferric oxide E00231 14789 Colorant
Gelatin E00630 Not Available Other agent
Lactose monohydrate E00393 104938 Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate E00208 11177 lubricant
Polyethylene glycol 4000 E00654 Not Available Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polyvinyl alcohol E00666 Not Available Coating agent; Emulsion stabilizing agent; Film/Membrane-forming agent
Povidone E00667 Not Available Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
Talc E00520 16211421 Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide E00322 26042 Coating agent; Colorant; Opacifying agent
Colcothar yellow E00436 518696 Colorant
Haematite red E00236 14833 Colorant
Hydrophobic colloidal silica E00285 24261 Anticaking agent; Emulsion stabilizing agent; Glidant; Suspending agent; Viscosity-controlling agent
Cellulose microcrystalline E00698 Not Available Adsorbent; Suspending agent; Diluent
⏷ Show the Full List of 15 Pharmaceutical Excipients of This Drug
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Ibrutinib 280mg tablet 280mg Tablet Oral
Ibrutinib 140mg tablet 140mg Tablet Oral
Ibrutinib 560mg tablet 560mg Tablet Oral
Ibrutinib 420mg tablet 420mg Tablet Oral
Ibrutinib 70mg capsule 70mg Capsule Oral
Ibrutinib 140mg capsule 140mg Capsule Oral
Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6912).
2 Janssen's IMBRUVICA (ibrutinib) Receives Additional European Commission Approval for the Treatment of Waldenstrom's Macroglobulinemia. Janssen-Cilag International NV (Janssen). Jul 10, 2015.
3 ClinicalTrials.gov (NCT01833039) An Open Label Treatment Use Protocol for Ibrutinib in Subjects With Relapsed or Refractory Mantle Cell Lymphoma. U.S. National Institutes of Health.
4 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
5 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
6 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1948).
7 P-Glycoprotein (MDR1/ABCB1) Restricts Brain Penetration of the Bruton's Tyrosine Kinase Inhibitor Ibrutinib, While Cytochrome P450-3A (CYP3A) Limits Its Oral Bioavailability. Mol Pharm. 2018 Nov 5;15(11):5124-5134.
8 Absorption, metabolism, and excretion of oral 14C radiolabeled ibrutinib: an open-label, phase I, single-dose study in healthy men. Drug Metab Dispos. 2015 Feb;43(2):289-97.
9 Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
10 Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
11 Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
12 Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
13 Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
14 Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
15 Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
16 The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
17 Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
18 Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5.
19 Effect of genetic polymorphism on the metabolism of endogenous neuroactive substances, progesterone and p-tyramine, catalyzed by CYP2D6. Brain Res Mol Brain Res. 2004 Oct 22;129(1-2):117-23.
20 CYP2D6 polymorphisms and tamoxifen metabolism: clinical relevance. Curr Oncol Rep. 2010 Jan;12(1):7-15.
21 Inhibition of cytochrome P450 2D6: structure-activity studies using a series of quinidine and quinine analogues. Chem Res Toxicol. 2003 Apr;16(4):450-9.
22 Effects of propofol on human hepatic microsomal cytochrome P450 activities. Xenobiotica. 1998 Sep;28(9):845-53.
23 Pharmacogenetics of schizophrenia. Am J Med Genet. 2000 Spring;97(1):98-106.
24 Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70.
25 Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab Rev. 2002 Feb-May;34(1-2):69-82.
26 Drug related genetic polymorphisms affecting adverse reactions to methotrexate, vinblastine, doxorubicin and cisplatin in patients with urothelial cancer. J Urol. 2008 Dec;180(6):2389-95.
27 Human prostate CYP3A5: identification of a unique 5'-untranslated sequence and characterization of purified recombinant protein. Biochem Biophys Res Commun. 1999 Jul 14;260(3):676-81.
28 Polymorphisms in cytochrome P4503A5 (CYP3A5) may be associated with race and tumor characteristics, but not metabolism and side effects of tamoxifen in breast cancer patients. Cancer Lett. 2005 Jan 10;217(1):61-72.
29 Drug Interactions Flockhart Table
30 Induction of hepatic CYP2E1 by a subtoxic dose of acetaminophen in rats: increase in dichloromethane metabolism and carboxyhemoglobin elevation. Drug Metab Dispos. 2007 Oct;35(10):1754-8.
31 Urinary 6 beta-hydroxycortisol excretion in rheumatoid arthritis. Br J Rheumatol. 1997 Jan;36(1):54-8.
32 Clinical pharmacokinetics of imatinib. Clin Pharmacokinet. 2005;44(9):879-94.
33 Kinetics and regulation of cytochrome P450-mediated etoposide metabolism. Drug Metab Dispos. 2004 Sep;32(9):993-1000.
34 Differential mechanism-based inhibition of CYP3A4 and CYP3A5 by verapamil. Drug Metab Dispos. 2005 May;33(5):664-71.
35 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
36 MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
37 Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
38 Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
39 Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
40 Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
41 Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.
42 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
43 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
44 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
45 Clinical pipeline report, company report or official report of InnoCare Pharma.
46 Targeting BTK in CLL: Beyond Ibrutinib. Curr Hematol Malig Rep. 2019 Jun;14(3):197-205.
47 Inhibition of Btk with CC-292 provides early pharmacodynamic assessment of activity in mice and humans. J Pharmacol Exp Ther. 2013 Aug;346(2):219-28.
48 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
49 Product Information. Calquence (acalabrutinib). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
50 Product Information. Imbruvica (ibrutinib). Pharmacyclics Inc, Sunnyvale, CA.
51 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
52 Product Information. Talzenna (talazoparib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
53 Cerner Multum, Inc. "Australian Product Information.".
54 Alderman CP, Moritz CK, Ben-Tovim DI "Abnormal platelet aggregation associated with fluoxetine therapy." Ann Pharmacother 26 (1992): 1517-9. [PMID: 1482806]
55 Agencia Espaola de Medicamentos y Productos Sanitarios Healthcare "Centro de informacion online de medicamentos de la AEMPS - CIMA.".
56 Agencia Espaola de Medicamentos y Productos Sanitarios Healthcare "Centro de informacion online de medicamentos de la AEMPS - CIMA.".
57 Product Information. Ubrelvy (ubrogepant). Allergan Inc, Irvine, CA.
58 Product Information. Nurtec ODT (rimegepant). Biohaven Pharmaceuticals, New Haven, CT.
59 Product Information. Ocrevus (ocrelizumab). Genentech, South San Francisco, CA.
60 Product Information. Xenleta (lefamulin). Nabriva Therapeutics US, Inc., King of Prussia, PA.
61 CDC. Centers for Disease Control and Prevention/ "Recommendations of the advisory committtee on immunization practices (ACIP): use of vaccines and immune globulins in persons with altered immunocompetence." MMWR Morb Mortal Wkly Rep 42(RR-04) (1993): 1-18. [PMID: 20300058]
62 EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring.".