Details of the Drug Combination

General Information of Drug Combination (ID: DCKI6Z3)

Drug Combination Name
Warfarin Isavuconazole
Indication
Disease Entry Status REF
Pharmacokinetics of Isavuconazole Phase 1 [1]
Component Drugs Warfarin   DMJYCVW Isavuconazole   DMSV12M
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Warfarin
Disease Entry ICD 11 Status REF
Atrial fibrillation BC81.3 Approved [2]
Deep vein thrombosis BD71 Approved [3]
Pulmonary hypertension BB01 Approved [3]
Thrombosis DB61-GB90 Application submitted [4]
Intracranial embolism 8B22.1 Investigative [3]
Venous thromboembolism BD72 Investigative [3]
Warfarin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Vitamin K epoxide reductase complex 1 (VKORC1) TTEUC8H VKOR1_HUMAN Inhibitor [11]
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Warfarin Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Substrate [12]
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Warfarin Interacts with 8 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [13]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [14]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [10]
Sulfotransferase 1A1 (SULT1A1) DEYWLRK ST1A1_HUMAN Metabolism [15]
Cytochrome P450 2C18 (CYP2C18) DEZMWRE CP2CI_HUMAN Metabolism [16]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [17]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [18]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [14]
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⏷ Show the Full List of 8 DME(s)
Warfarin Interacts with 52 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Decreases Expression [19]
Cytochrome P450 2C9 (CYP2C9) OTGLBN29 CP2C9_HUMAN Increases Response To Substance [20]
Cytochrome P450 2C19 (CYP2C19) OTFMJYYE CP2CJ_HUMAN Affects Response To Substance [21]
Cytochrome P450 2C8 (CYP2C8) OTHCWT42 CP2C8_HUMAN Affects Response To Substance [22]
Cytochrome P450 2C18 (CYP2C18) OTY687L9 CP2CI_HUMAN Affects Response To Substance [21]
Solute carrier organic anion transporter family member 1B3 (SLCO1B3) OTOM3BUH SO1B3_HUMAN Affects Response To Substance [23]
Cytochrome P450 4F2 (CYP4F2) OTKILAER CP4F2_HUMAN Increases Response To Substance [24]
Cytochrome P450 2D6 (CYP2D6) OTZJC802 CP2D6_HUMAN Decreases Activity [25]
Nuclear receptor subfamily 1 group I member 2 (NR1I2) OTC5U0N5 NR1I2_HUMAN Decreases Expression [19]
Prothrombin (F2) OTNFSM49 THRB_HUMAN Decreases Expression [26]
Antithrombin-III (SERPINC1) OTDFATG0 ANT3_HUMAN Increases Expression [27]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Decreases Expression [28]
Albumin (ALB) OTVMM513 ALBU_HUMAN Affects Binding [29]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Degradation [30]
Coagulation factor VII (F7) OTGNJ97M FA7_HUMAN Decreases Expression [26]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Expression [7]
Cadherin-1 (CDH1) OTFJMXPM CADH1_HUMAN Increases Expression [7]
Arachidonate 5-lipoxygenase-activating protein (ALOX5AP) OT0DH40W AL5AP_HUMAN Increases Expression [31]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Expression [7]
Arylsulfatase L (ARSL) OTF1VTCR ARSL_HUMAN Decreases Activity [32]
Growth arrest-specific protein 6 (GAS6) OTPOPUUE GAS6_HUMAN Decreases Carboxylation [7]
Endomucin (EMCN) OTS03CZC MUCEN_HUMAN Decreases Expression [7]
Serine protease 53 (PRSS53) OT3HUUI3 PRS53_HUMAN Affects Response To Substance [33]
Aspartyl/asparaginyl beta-hydroxylase (ASPH) OT3KGDEE ASPH_HUMAN Affects Response To Substance [34]
Ephrin type-A receptor 7 (EPHA7) OT3VC211 EPHA7_HUMAN Affects Response To Substance [35]
Myosin-6 (MYH6) OT3YNCH1 MYH6_HUMAN Affects Response To Substance [36]
Apolipoprotein A-I (APOA1) OT5THARI APOA1_HUMAN Affects Response To Substance [37]
Epoxide hydrolase 1 (EPHX1) OTBKWQER HYEP_HUMAN Increases Response To Substance [38]
Coagulation factor V (F5) OTDMZ3LT FA5_HUMAN Affects Response To Substance [21]
Solute carrier family 15 member 2 (SLC15A2) OTDV7YES S15A2_HUMAN Affects Response To Substance [23]
Vitamin K-dependent gamma-carboxylase (GGCX) OTE0FNAP VKGC_HUMAN Decreases Response To Substance [6]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Affects Response To Substance [39]
Apolipoprotein E (APOE) OTFOWL2H APOE_HUMAN Affects Response To Substance [40]
E3 ubiquitin-protein ligase NEDD4 (NEDD4) OTFPXLXT NEDD4_HUMAN Affects Response To Substance [34]
Vitamin K-dependent protein C (PROC) OTGVH484 PROC_HUMAN Increases Response To Substance [38]
Apolipoprotein B-100 (APOB) OTH0UOCZ APOB_HUMAN Affects Response To Substance [41]
Prolow-density lipoprotein receptor-related protein 1 (LRP1) OTHTEH4G LRP1_HUMAN Affects Response To Substance [37]
Tyrosine-protein kinase receptor UFO (AXL) OTKA2SUX UFO_HUMAN Increases Response To Substance [7]
Transcription factor GATA-6 (GATA6) OTO2BC0F GATA6_HUMAN Affects Response To Substance [42]
Transcription factor GATA-4 (GATA4) OTQHWAZG GATA4_HUMAN Affects Response To Substance [42]
Fibroblast growth factor 5 (FGF5) OTQXGHBY FGF5_HUMAN Affects Response To Substance [43]
Cytochrome P450 3A5 (CYP3A5) OTSXFBXB CP3A5_HUMAN Affects Response To Substance [21]
Calumenin (CALU) OTSYQN71 CALU_HUMAN Affects Response To Substance [44]
Coagulation factor IX (F9) OTT0CX3Q FA9_HUMAN Increases Response To Substance [45]
Heme A synthase COX15 (COX15) OTUIYHIW COX15_HUMAN Affects Response To Substance [43]
NADPH--cytochrome P450 reductase (POR) OTVIDOCH NCPR_HUMAN Affects Response To Substance [46]
Folylpolyglutamate synthase, mitochondrial (FPGS) OTW3F1ZE FOLC_HUMAN Affects Response To Substance [47]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) OTW8V2V1 ABCG2_HUMAN Affects Response To Substance [48]
Phospholipase DDHD1 (DDHD1) OTWTHOWK DDHD1_HUMAN Affects Response To Substance [34]
Vitamin K-dependent protein S (PROS1) OTXQWNOI PROS_HUMAN Affects Response To Substance [21]
NAD(P)H dehydrogenase 1 (NQO1) OTZGGIVK NQO1_HUMAN Affects Response To Substance [49]
Alpha-1-acid glycoprotein 1 (ORM1) OTZKSBRE A1AG1_HUMAN Increases Response To Substance [38]
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⏷ Show the Full List of 52 DOT(s)
Indication(s) of Isavuconazole
Disease Entry ICD 11 Status REF
Candidemia 1F23.3Y Phase 3 [5]
Invasive aspergillosis 1F20.0 Phase 3 [5]
Invasive candidiasis 1F23 Phase 3 [5]
Isavuconazole Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [50]
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References

1 ClinicalTrials.gov (NCT01657825) Drug Interaction Study of Isavuconazole and Warfarin in Healthy Male Subjects
2 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: 6853).
3 Warfarin FDA Label
4 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
5 ClinicalTrials.gov (NCT00634049) Isavuconazole in the Treatment of Renally Impaired Aspergillosis and Rare Fungi. U.S. National Institutes of Health.
6 The influence of sequence variations in factor VII, gamma-glutamyl carboxylase and vitamin K epoxide reductase complex genes on warfarin dose requirement. Thromb Haemost. 2006 May;95(5):782-7.
7 Warfarin Blocks Gas6-Mediated Axl Activation Required for Pancreatic Cancer Epithelial Plasticity and Metastasis. Cancer Res. 2015 Sep 15;75(18):3699-705. doi: 10.1158/0008-5472.CAN-14-2887-T. Epub 2015 Jul 23.
8 Influence of NR3C1 and VDR polymorphisms on stable warfarin dose in patients with mechanical cardiac valves. Int J Cardiol. 2017 Jun 1;236:393-397. doi: 10.1016/j.ijcard.2017.02.103. Epub 2017 Feb 24.
9 Association between VEGFA gene polymorphisms and bleeding complications in patients maintaining therapeutic international normalized ratio. Pharmacogenomics. 2019 Jun;20(9):659-667. doi: 10.2217/pgs-2019-0005. Epub 2019 May 8.
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19 Warfarin calcifies human aortic valve interstitial cells at high-phosphate conditions via pregnane X receptor. J Bone Miner Metab. 2019 Nov;37(6):944-956. doi: 10.1007/s00774-019-01001-3. Epub 2019 Apr 8.
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22 Profiling of warfarin pharmacokinetics-associated genetic variants: Black Africans portray unique genetic markers important for an African specific warfarin pharmacogenetics-dosing algorithm. J Thromb Haemost. 2021 Dec;19(12):2957-2973. doi: 10.1111/jth.15494. Epub 2021 Sep 29.
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33 Evaluation of the effects of VKORC1 polymorphisms and haplotypes, CYP2C9 genotypes, and clinical factors on warfarin response in Sudanese patients. Eur J Clin Pharmacol. 2011 Nov;67(11):1119-30. doi: 10.1007/s00228-011-1060-1. Epub 2011 May 18.
34 Genetic determinants of warfarin maintenance dose and time in therapeutic treatment range: a RE-LY genomics substudy. Pharmacogenomics. 2016 Aug;17(13):1425-39. doi: 10.2217/pgs-2016-0061. Epub 2016 Aug 4.
35 Association of Genetic Variants With Warfarin-Associated Bleeding Among Patients of African Descent. JAMA. 2018 Oct 23;320(16):1670-1677. doi: 10.1001/jama.2018.14955.
36 Association of the MYH6 Gene Polymorphism with the Risk of Atrial Fibrillation and Warfarin Anticoagulation Therapy. Genet Test Mol Biomarkers. 2021 Sep;25(9):590-599. doi: 10.1089/gtmb.2021.0025. Epub 2021 Sep 9.
37 LRP1 and APOA1 Polymorphisms: Impact on Warfarin International Normalized Ratio-Related Phenotypes. J Cardiovasc Pharmacol. 2020 Jul;76(1):71-76. doi: 10.1097/FJC.0000000000000834.
38 Building individualized medicine: prevention of adverse reactions to warfarin therapy. J Pharmacol Exp Ther. 2007 Aug;322(2):427-34. doi: 10.1124/jpet.106.117952. Epub 2007 May 11.
39 Is there a role for MDR1, EPHX1 and protein Z gene variants in modulation of warfarin dosage? a study on a cohort of the Egyptian population. Mol Diagn Ther. 2014 Feb;18(1):73-83. doi: 10.1007/s40291-013-0055-2.
40 Genetic and nongenetic factors associated with warfarin dose requirements in Egyptian patients. Pharmacogenet Genomics. 2011 Mar;21(3):130-5. doi: 10.1097/FPC.0b013e3283436b86.
41 APOB gene polymorphisms may affect the risk of minor or minimal bleeding complications in patients on warfarin maintaining therapeutic INR. Eur J Hum Genet. 2019 Oct;27(10):1542-1549. doi: 10.1038/s41431-019-0450-1. Epub 2019 Jun 11.
42 Genetic variations in the transcription factors GATA4 and GATA6 and bleeding complications in patients receiving warfarin therapy. Drug Des Devel Ther. 2019 May 17;13:1717-1727. doi: 10.2147/DDDT.S198018. eCollection 2019.
43 Influence of common and rare genetic variation on warfarin dose among African-Americans and European-Americans using the exome array. Pharmacogenomics. 2017 Jul;18(11):1059-1073. doi: 10.2217/pgs-2017-0046. Epub 2017 Jul 7.
44 Genetic determinants of variability in warfarin response after the dose-titration phase. Pharmacogenet Genomics. 2016 Nov;26(11):510-516. doi: 10.1097/FPC.0000000000000244.
45 Variants in FIX propeptide associated with vitamin K antagonist hypersensitivity: functional analysis and additional data confirming the common founder mutations. Ann Hematol. 2018 Jun;97(6):1061-1069. doi: 10.1007/s00277-018-3264-2. Epub 2018 Feb 15.
46 Influence of genetic polymorphisms in cytochrome P450 oxidoreductase on the variability in stable warfarin maintenance dose in Han Chinese. Eur J Clin Pharmacol. 2016 Nov;72(11):1327-1334. doi: 10.1007/s00228-016-2098-x. Epub 2016 Aug 4.
47 Genetic variant in folate homeostasis is associated with lower warfarin dose in African Americans. Blood. 2014 Oct 2;124(14):2298-305. doi: 10.1182/blood-2014-04-568436. Epub 2014 Jul 30.
48 Association between ABCG2 and ABCB1 genes and warfarin stability: a case-control study. Thromb Res. 2014 Dec;134(6):1359-62. doi: 10.1016/j.thromres.2014.09.017. Epub 2014 Sep 20.
49 Effects of NAD(P)H quinone oxidoreductase 1 polymorphisms on stable warfarin doses in Korean patients with mechanical cardiac valves. Eur J Clin Pharmacol. 2015 Oct;71(10):1229-36. doi: 10.1007/s00228-015-1915-y. Epub 2015 Aug 11.
50 Pharmacokinetic evaluation of CYP3A4-mediated drug-drug interactions of isavuconazole with rifampin, ketoconazole, midazolam, and ethinyl estradiol/norethindrone in healthy adults. Clin Pharmacol Drug Dev. 2017 Jan;6(1):44-53.