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Identification
NameDabigatran etexilate
Accession NumberDB06695
TypeSmall Molecule
GroupsApproved
Description

Dabigatran etexilate is an oral prodrug that is metabolized by a serum esterase to dabigatran. It is a synthetic, competitive and reversible direct thrombin inhibitor. Inhibition of thrombin disrupts the coagulation cascade and inhibits the formation of clots. Dabigatran etexilate may be used to decrease the risk of venous thromboembolic events in patients who have undergone total hip or knee replacement surgery, or to prevent stroke and systemic embolism in patients with atrial fibrillation, in whom anticoagulation therapy is indicated. In contrast to warfarin, because its anticoagulant effects are predictable, lab monitoring is not necessary. FDA approved on October 19, 2010.

Structure
Thumb
Synonyms
Dabigatran
Ethyl 3-[[[4-[[[(hexyloxyl)carbonyl]amino]iminomethyl]phenyl]amino]methyl]-1-methyl-1H-benzimidazol-5-yl]carbonyl](pyridin-2-yl)amino] propanoate
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Pradaxacapsule110 mg/1oralBoehringer Ingelheim Pharmaceuticals Inc.2015-11-23Not applicableUs
Pradaxacapsule150 mgoralBoehringer Ingelheim (Canada) Ltd Ltee2010-11-03Not applicableCanada
Pradaxacapsule110 mgoralBoehringer Ingelheim (Canada) Ltd Ltee2008-07-03Not applicableCanada
Pradaxacapsule75 mgoralBoehringer Ingelheim (Canada) Ltd Ltee2008-07-03Not applicableCanada
Pradaxacapsule150 mg/1oralRebel Distributors Corp2010-10-26Not applicableUs
Pradaxacapsule75 mg/1oralBoehringer Ingelheim Pharmaceuticals Inc.2011-08-08Not applicableUs
Pradaxacapsule150 mg/1oralBoehringer Ingelheim Pharmaceuticals Inc.2010-10-26Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
PradaxBoehringer Ingelheim
RendixNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Dabigatran etexilate mesilate
Thumb
  • InChI Key: XETBXHPXHHOLOE-UHFFFAOYSA-N
  • Monoisotopic Mass: 723.305032141
  • Average Mass: 723.839
DBSALT000035
Categories
UNII2E18WX195X
CAS number211915-06-9
WeightAverage: 627.7332
Monoisotopic: 627.316917457
Chemical FormulaC34H41N7O5
InChI KeyInChIKey=KSGXQBZTULBEEQ-UHFFFAOYSA-N
InChI
InChI=1S/C34H41N7O5/c1-4-6-7-10-21-46-34(44)39-32(35)24-12-15-26(16-13-24)37-23-30-38-27-22-25(14-17-28(27)40(30)3)33(43)41(20-18-31(42)45-5-2)29-11-8-9-19-36-29/h8-9,11-17,19,22,37H,4-7,10,18,20-21,23H2,1-3H3,(H2,35,39,44)
IUPAC Name
ethyl 3-(1-{2-[({4-[amino({[(hexyloxy)carbonyl]imino})methyl]phenyl}amino)methyl]-1-methyl-1H-1,3-benzodiazol-5-yl}-N-(pyridin-2-yl)formamido)propanoate
SMILES
CCCCCCOC(=O)N=C(N)C1=CC=C(NCC2=NC3=C(C=CC(=C3)C(=O)N(CCC(=O)OCC)C3=CC=CC=N3)N2C)C=C1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as benzimidazoles. These are organic compounds containing a benzene ring fused to an imidazole ring (five member ring containing a nitrogen atom, 4 carbon atoms, and two double bonds).
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzimidazoles
Sub ClassNot Available
Direct ParentBenzimidazoles
Alternative Parents
Substituents
  • Benzimidazole
  • Benzamide
  • Phenylalkylamine
  • Substituted aniline
  • Benzoyl
  • Aralkylamine
  • Secondary aliphatic/aromatic amine
  • Aniline
  • Aminopyridine
  • Imidolactam
  • Benzenoid
  • Pyridine
  • N-substituted imidazole
  • Dicarboxylic acid or derivatives
  • Monocyclic benzene moiety
  • Heteroaromatic compound
  • Imidazole
  • Azole
  • Tertiary amine
  • Carboxylic acid ester
  • Carboxamide group
  • Azacycle
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Carboximidamide
  • Secondary amine
  • Carboxylic acid derivative
  • Carboxylic acid amidine
  • Amidine
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationDabigatran is indicated for the prevention of venous thromboembolic events in patients who have undergone elective hip or knee replacement surgery (based on RE-NOVATE, RE-MODEL, and RE-MOBILIZE trials). In 2010, it was approved in the US and Canada for prevention of stroke and systemic embolism in patients with atrial fibrillation (approval based on the RE-LY trial). Contraindications: severe renal impairment (CrCL < 30 ml/min); haemorrhagic manifestations, bleeding diathesis or spontaneous or pharmacologic impairment of haemostasis; lesions at risk of clinically significant bleeding (e.g. extensive cerebral infarction (haemorrhagic or ischemic) in the last 6 months, active peptic ulcer disease); concomitant treatment with P-glycoprotein inhibitors (e.g. oral ketoconazole, verapamil); and those with known hypersensitivity to dabigatran, dabigatran etexilate or any ingredient used in the formulation or component of the container. As of December 2012, dabigatran is contraindicated in patients with mechanical prosthetic heart valves.
PharmacodynamicsDabigatran directly inhibits thrombin in a concentration-dependent, reversible, specific, and competitive manner which results in a prolongation of aPTT (partial thromboplastin time), ECT (Ecarin clotting time), and TT (thrombin time). It may increase INR but this laboratory parameter is relatively insensitive to the activity of dabigatran.
Mechanism of actionDabigatran etexilate is an inactive pro-drug that is converted to dabigatran, the active form, by esterase-catalyzed hydrolysis in the plasma and liver. Dabigatran, the main active principle in plasma, is a rapid-acting competitive and reversible direct inhibitor of thrombin. Thrombin, a serine protease, is responsible for the conversion of fibrinogen to fibrin in the coagulation cascade. Inhibition of thrombin consequently prevents thrombus development. Dabigatran inhibits free thrombin, fibrin-bound thrombin and thrombin-induced platelet aggregation.
Related Articles
AbsorptionPeak plasma concentrations were achieved in 6 hours in post surgical patients. In healthy patients, maximum concentrations were achieved in 0.5 to 2 hours. The absolute bioavailability of dabigatran in the body after administration of dabigatran etexilate was 6.5%. Food does not affect the bioavailability of dabigatran etexilate, but it delays the time to peak plasma concentrations by 2 hours. Oral bioavailability may increase by up to 75% when pellets are taken out of the hydroxypropylmethylcellulose (HPMC) capsule. Therefore, capsules should not be opened and pellets taken alone. Furthermore, although absorption of dabigatran etexilate is independent of gastrointestinal acidity, coadministration of pantoprazole (proton pump inhibitor) may reduce the bioavailability of dabigatran. Despite this finding, dose adjustment is not required.
Volume of distribution

Moderate tissue distribution with a Vd of 60-70L.
Accumulation factor, twice daily dosing = 2

Protein bindingRelatively low binding (34-35%) to plasma proteins.
Metabolism

CYP450 enzymes are not involved in the metabolism of dabigatran thus is not expected to interact with drugs metabolized by CYP isoenzymes. Dabigatran is typically metabolised by esterases and microsomal carboxylesterases. Pharmacologically active acylglucoronides are formed via conjugation. Four positional isomers, 1-O, 2-O, 3-O, and 4-O, acylglucuronides exist, each accounting for less than 10% of total plasma dabagatran.

Route of eliminationMainly excreted in urine (85%). Fecal excretion accounts for 6% of the orally administered dose. Dabigatran is primarily eliminated unchanged via the kidneys at a rate of 100 ml/min corresponding to the glomerular filtration rate.
Half life12-14 hours in healthy volunteers. 14-17 hours in patients treated for prevention of venous thromboembolism following hip- or knee-replacement surgery.
ClearanceNot Available
ToxicityThe most common adverse reactions include dyspepsia or gastritis-like symptoms. The approximate lethal dose (LD50) in rats and mice was observed at single oral doses of > 2000 mg/kg. Oral doses of 600 mg/kg did not induce any toxicologically meaningful changes in dogs and Rhesus monkeys. Dabigatran was well-tolerated in rats and Rhesus monkeys during repeat-dose toxicity studies. No evidence of mutagenic potential.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.942
Blood Brain Barrier+0.8673
Caco-2 permeable-0.7014
P-glycoprotein substrateSubstrate0.7412
P-glycoprotein inhibitor IInhibitor0.7539
P-glycoprotein inhibitor IIInhibitor0.8443
Renal organic cation transporterNon-inhibitor0.701
CYP450 2C9 substrateNon-substrate0.858
CYP450 2D6 substrateNon-substrate0.837
CYP450 3A4 substrateSubstrate0.6154
CYP450 1A2 substrateNon-inhibitor0.6906
CYP450 2C9 inhibitorNon-inhibitor0.5102
CYP450 2D6 inhibitorNon-inhibitor0.8417
CYP450 2C19 inhibitorInhibitor0.5157
CYP450 3A4 inhibitorInhibitor0.781
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5789
Ames testNon AMES toxic0.6292
CarcinogenicityNon-carcinogens0.8065
BiodegradationNot ready biodegradable0.9931
Rat acute toxicity2.7093 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9047
hERG inhibition (predictor II)Inhibitor0.6181
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Capsuleoral110 mg/1
Capsuleoral110 mg
Capsuleoral150 mg
Capsuleoral150 mg/1
Capsuleoral75 mg
Capsuleoral75 mg/1
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6087380 No1998-02-182018-02-18Us
US7866474 No2007-08-312027-08-31Us
US7932273 No2005-09-072025-09-07Us
US9034822 No2011-01-202031-01-20Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point180 +/- 3 (DSC: 10 K min^-1 heating rate)Not Available
water solubility1.8mg/ml, partly soluble MSDS
logP3.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00466 mg/mLALOGPS
logP5.17ALOGPS
logP4.59ChemAxon
logS-5.1ALOGPS
pKa (Strongest Acidic)17.89ChemAxon
pKa (Strongest Basic)3.87ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area154.03 Å2ChemAxon
Rotatable Bond Count17ChemAxon
Refractivity176.43 m3·mol-1ChemAxon
Polarizability71.11 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
References
Synthesis Reference

Christian Filser, Wolfgang Dersch, Rainer Hamm, Arndt Hausherr, Gunter Koch, Ulrich Scholz, Georg Zerban, “METHOD FOR PRODUCING AN INTERMEDIATE PRODUCT OF DABIGATRAN ETEXILATE.” U.S. Patent US20110118471, issued May 19, 2011.

US20110118471
General References
  1. Bauer KA: New oral anticoagulants in development: potential for improved safety profiles. Rev Neurol Dis. 2010;7(1):1-8. [PubMed:20410856 ]
  2. Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J, Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis BS, Darius H, Diener HC, Joyner CD, Wallentin L: Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009 Sep 17;361(12):1139-51. doi: 10.1056/NEJMoa0905561. Epub 2009 Aug 30. [PubMed:19717844 ]
  3. Wolowacz SE, Roskell NS, Plumb JM, Caprini JA, Eriksson BI: Efficacy and safety of dabigatran etexilate for the prevention of venous thromboembolism following total hip or knee arthroplasty. A meta-analysis. Thromb Haemost. 2009 Jan;101(1):77-85. [PubMed:19132192 ]
  4. Ginsberg JS, Davidson BL, Comp PC, Francis CW, Friedman RJ, Huo MH, Lieberman JR, Muntz JE, Raskob GE, Clements ML, Hantel S, Schnee JM, Caprini JA: Oral thrombin inhibitor dabigatran etexilate vs North American enoxaparin regimen for prevention of venous thromboembolism after knee arthroplasty surgery. J Arthroplasty. 2009 Jan;24(1):1-9. doi: 10.1016/j.arth.2008.01.132. Epub 2008 Apr 14. [PubMed:18534438 ]
  5. Eriksson BI, Dahl OE, Buller HR, Hettiarachchi R, Rosencher N, Bravo ML, Ahnfelt L, Piovella F, Stangier J, Kalebo P, Reilly P: A new oral direct thrombin inhibitor, dabigatran etexilate, compared with enoxaparin for prevention of thromboembolic events following total hip or knee replacement: the BISTRO II randomized trial. J Thromb Haemost. 2005 Jan;3(1):103-11. [PubMed:15634273 ]
  6. Di Nisio M, Middeldorp S, Buller HR: Direct thrombin inhibitors. N Engl J Med. 2005 Sep 8;353(10):1028-40. [PubMed:16148288 ]
  7. Stangier J, Eriksson BI, Dahl OE, Ahnfelt L, Nehmiz G, Stahle H, Rathgen K, Svard R: Pharmacokinetic profile of the oral direct thrombin inhibitor dabigatran etexilate in healthy volunteers and patients undergoing total hip replacement. J Clin Pharmacol. 2005 May;45(5):555-63. [PubMed:15831779 ]
  8. Ezekowitz MD, Reilly PA, Nehmiz G, Simmers TA, Nagarakanti R, Parcham-Azad K, Pedersen KE, Lionetti DA, Stangier J, Wallentin L: Dabigatran with or without concomitant aspirin compared with warfarin alone in patients with nonvalvular atrial fibrillation (PETRO Study). Am J Cardiol. 2007 Nov 1;100(9):1419-26. Epub 2007 Aug 17. [PubMed:17950801 ]
  9. Eriksson BI, Dahl OE, Rosencher N, Kurth AA, van Dijk CN, Frostick SP, Kalebo P, Christiansen AV, Hantel S, Hettiarachchi R, Schnee J, Buller HR: Oral dabigatran etexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE-MODEL randomized trial. J Thromb Haemost. 2007 Nov;5(11):2178-85. [PubMed:17764540 ]
  10. Eriksson BI, Dahl OE, Rosencher N, Kurth AA, van Dijk CN, Frostick SP, Prins MH, Hettiarachchi R, Hantel S, Schnee J, Buller HR: Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial. Lancet. 2007 Sep 15;370(9591):949-56. [PubMed:17869635 ]
  11. Scaglione F: New oral anticoagulants: comparative pharmacology with vitamin K antagonists. Clin Pharmacokinet. 2013 Feb;52(2):69-82. doi: 10.1007/s40262-012-0030-9. [PubMed:23292752 ]
External Links
ATC CodesB01AE07
AHFS Codes
  • 20:12.04.12
PDB EntriesNot Available
FDA labelDownload (431 KB)
MSDSDownload (99.2 KB)
Interactions
Drug Interactions
Drug
AbciximabAbciximab may increase the anticoagulant activities of Dabigatran etexilate.
AbirateroneThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Abiraterone.
AcenocoumarolDabigatran etexilate may increase the anticoagulant activities of Acenocoumarol.
Acetylsalicylic acidAcetylsalicylic acid may increase the anticoagulant activities of Dabigatran etexilate.
AlteplaseAlteplase may increase the anticoagulant activities of Dabigatran etexilate.
Aluminum hydroxideThe serum concentration of Dabigatran etexilate can be decreased when it is combined with Aluminum hydroxide.
AmiodaroneThe serum concentration of Dabigatran etexilate can be increased when it is combined with Amiodarone.
AnagrelideAnagrelide may increase the anticoagulant activities of Dabigatran etexilate.
AnistreplaseAnistreplase may increase the anticoagulant activities of Dabigatran etexilate.
ApixabanDabigatran etexilate may increase the anticoagulant activities of Apixaban.
ArgatrobanDabigatran etexilate may increase the anticoagulant activities of Argatroban.
AtorvastatinThe serum concentration of Dabigatran etexilate can be decreased when it is combined with Atorvastatin.
AzithromycinThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Azithromycin.
BivalirudinDabigatran etexilate may increase the anticoagulant activities of Bivalirudin.
Calcium carbonateThe serum concentration of Dabigatran etexilate can be decreased when it is combined with Calcium carbonate.
CangrelorCangrelor may increase the anticoagulant activities of Dabigatran etexilate.
CarbamazepineThe serum concentration of Dabigatran etexilate can be decreased when it is combined with Carbamazepine.
CarvedilolThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Carvedilol.
ChlorotrianiseneChlorotrianisene may decrease the anticoagulant activities of Dabigatran etexilate.
CilostazolCilostazol may increase the anticoagulant activities of Dabigatran etexilate.
CitalopramCitalopram may increase the anticoagulant activities of Dabigatran etexilate.
Citric AcidDabigatran etexilate may increase the anticoagulant activities of Citric Acid.
ClarithromycinThe serum concentration of Dabigatran etexilate can be increased when it is combined with Clarithromycin.
ClopidogrelClopidogrel may increase the anticoagulant activities of Dabigatran etexilate.
CobicistatThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Cobicistat.
CollagenaseThe risk or severity of adverse effects can be increased when Dabigatran etexilate is combined with Collagenase.
CrizotinibThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Crizotinib.
CyclosporineThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Cyclosporine.
DaclatasvirThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Daclatasvir.
DalteparinDabigatran etexilate may increase the anticoagulant activities of Dalteparin.
DanaparoidDabigatran etexilate may increase the anticoagulant activities of Danaparoid.
DarunavirThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Darunavir.
DasatinibDasatinib may increase the anticoagulant activities of Dabigatran etexilate.
DeferasiroxThe risk or severity of adverse effects can be increased when Dabigatran etexilate is combined with Deferasirox.
Deoxycholic AcidThe risk or severity of adverse effects can be increased when Dabigatran etexilate is combined with Deoxycholic Acid.
DesirudinDabigatran etexilate may increase the anticoagulant activities of Desirudin.
DesogestrelThe therapeutic efficacy of Dabigatran etexilate can be decreased when used in combination with Desogestrel.
DesvenlafaxineDesvenlafaxine may increase the anticoagulant activities of Dabigatran etexilate.
DiclofenacDiclofenac may increase the anticoagulant activities of Dabigatran etexilate.
DicoumarolDabigatran etexilate may increase the anticoagulant activities of Dicoumarol.
DiflunisalDiflunisal may increase the anticoagulant activities of Dabigatran etexilate.
DipyridamoleThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Dipyridamole.
DronedaroneThe serum concentration of Dabigatran etexilate can be increased when it is combined with Dronedarone.
DuloxetineDuloxetine may increase the anticoagulant activities of Dabigatran etexilate.
DydrogesteroneThe therapeutic efficacy of Dabigatran etexilate can be decreased when used in combination with Dydrogesterone.
Edetic AcidDabigatran etexilate may increase the anticoagulant activities of Edetic Acid.
EdoxabanEdoxaban may increase the anticoagulant activities of Dabigatran etexilate.
EliglustatThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Eliglustat.
EnoxaparinDabigatran etexilate may increase the anticoagulant activities of Enoxaparin.
EptifibatideEptifibatide may increase the anticoagulant activities of Dabigatran etexilate.
ErythromycinThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Erythromycin.
EscitalopramEscitalopram may increase the anticoagulant activities of Dabigatran etexilate.
EsomeprazoleThe serum concentration of the active metabolites of Dabigatran etexilate can be reduced when Dabigatran etexilate is used in combination with Esomeprazole resulting in a loss in efficacy.
Ethyl biscoumacetateDabigatran etexilate may increase the anticoagulant activities of Ethyl biscoumacetate.
EtodolacEtodolac may increase the anticoagulant activities of Dabigatran etexilate.
FenoprofenFenoprofen may increase the anticoagulant activities of Dabigatran etexilate.
FlibanserinThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Flibanserin.
FloctafenineFloctafenine may increase the anticoagulant activities of Dabigatran etexilate.
FluoxetineFluoxetine may increase the anticoagulant activities of Dabigatran etexilate.
FlurbiprofenFlurbiprofen may increase the anticoagulant activities of Dabigatran etexilate.
FluvoxamineFluvoxamine may increase the anticoagulant activities of Dabigatran etexilate.
Fondaparinux sodiumDabigatran etexilate may increase the anticoagulant activities of Fondaparinux sodium.
FosphenytoinThe serum concentration of Dabigatran etexilate can be decreased when it is combined with Fosphenytoin.
GestodeneThe therapeutic efficacy of Dabigatran etexilate can be decreased when used in combination with Gestodene.
HeparinDabigatran etexilate may increase the anticoagulant activities of Heparin.
Ibritumomab tiuxetanThe risk or severity of adverse effects can be increased when Dabigatran etexilate is combined with Ibritumomab.
IbrutinibThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Ibrutinib.
IbuprofenIbuprofen may increase the anticoagulant activities of Dabigatran etexilate.
IndomethacinIndomethacin may increase the anticoagulant activities of Dabigatran etexilate.
InfliximabInfliximab may increase the anticoagulant activities of Dabigatran etexilate.
ItraconazoleThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Itraconazole.
IvacaftorThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Ivacaftor.
KetoconazoleThe serum concentration of Dabigatran etexilate can be increased when it is combined with Ketoconazole.
KetoprofenKetoprofen may increase the anticoagulant activities of Dabigatran etexilate.
KetorolacKetorolac may increase the anticoagulant activities of Dabigatran etexilate.
LansoprazoleThe serum concentration of the active metabolites of Dabigatran etexilate can be reduced when Dabigatran etexilate is used in combination with Lansoprazole resulting in a loss in efficacy.
LapatinibThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Lapatinib.
LevomilnacipranLevomilnacipran may increase the anticoagulant activities of Dabigatran etexilate.
LimaprostThe risk or severity of adverse effects can be increased when Limaprost is combined with Dabigatran etexilate.
LomitapideThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Lomitapide.
LumacaftorThe serum concentration of Dabigatran etexilate can be decreased when it is combined with Lumacaftor.
Magnesium hydroxideThe serum concentration of Dabigatran etexilate can be decreased when it is combined with Magnesium hydroxide.
Magnesium oxideThe serum concentration of Dabigatran etexilate can be decreased when it is combined with Magnesium oxide.
Mefenamic acidMefenamic acid may increase the anticoagulant activities of Dabigatran etexilate.
MefloquineThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Mefloquine.
MeloxicamMeloxicam may increase the anticoagulant activities of Dabigatran etexilate.
MilnacipranMilnacipran may increase the anticoagulant activities of Dabigatran etexilate.
MirabegronThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Mirabegron.
NabumetoneNabumetone may increase the anticoagulant activities of Dabigatran etexilate.
NadroparinDabigatran etexilate may increase the anticoagulant activities of Nadroparin.
NaproxenNaproxen may increase the anticoagulant activities of Dabigatran etexilate.
NicardipineThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Nicardipine.
NilotinibThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Nilotinib.
NintedanibThe risk or severity of adverse effects can be increased when Dabigatran etexilate is combined with Nintedanib.
ObinutuzumabThe risk or severity of adverse effects can be increased when Dabigatran etexilate is combined with Obinutuzumab.
Omacetaxine mepesuccinateThe risk or severity of adverse effects can be increased when Dabigatran etexilate is combined with Homoharringtonine.
Omega-3 fatty acidsOmega-3 fatty acids may increase the anticoagulant activities of Dabigatran etexilate.
OmeprazoleThe serum concentration of the active metabolites of Dabigatran etexilate can be reduced when Dabigatran etexilate is used in combination with Omeprazole resulting in a loss in efficacy.
OxaprozinOxaprozin may increase the anticoagulant activities of Dabigatran etexilate.
PantoprazoleThe serum concentration of the active metabolites of Dabigatran etexilate can be reduced when Dabigatran etexilate is used in combination with Pantoprazole resulting in a loss in efficacy.
ParoxetineParoxetine may increase the anticoagulant activities of Dabigatran etexilate.
Pentosan PolysulfatePentosan Polysulfate may increase the anticoagulant activities of Dabigatran etexilate.
PhenindioneDabigatran etexilate may increase the anticoagulant activities of Phenindione.
PhenobarbitalThe serum concentration of Dabigatran etexilate can be decreased when it is combined with Phenobarbital.
PhenprocoumonDabigatran etexilate may increase the anticoagulant activities of Phenprocoumon.
PhenytoinThe serum concentration of Dabigatran etexilate can be decreased when it is combined with Phenytoin.
PiroxicamPiroxicam may increase the anticoagulant activities of Dabigatran etexilate.
PrasugrelPrasugrel may increase the anticoagulant activities of Dabigatran etexilate.
PrimidoneThe serum concentration of Dabigatran etexilate can be decreased when it is combined with Primidone.
ProgesteroneThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Progesterone.
PropranololThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Propranolol.
QuinidineThe serum concentration of Dabigatran etexilate can be increased when it is combined with Quinidine.
QuinineThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Quinine.
RabeprazoleThe serum concentration of the active metabolites of Dabigatran etexilate can be reduced when Dabigatran etexilate is used in combination with Rabeprazole resulting in a loss in efficacy.
RanolazineThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Ranolazine.
ReserpineThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Reserpine.
ReteplaseReteplase may increase the anticoagulant activities of Dabigatran etexilate.
RidogrelRidogrel may increase the anticoagulant activities of Dabigatran etexilate.
RifampicinThe serum concentration of Dabigatran etexilate can be decreased when it is combined with Rifampicin.
RitonavirThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Ritonavir.
RivaroxabanDabigatran etexilate may increase the anticoagulant activities of Rivaroxaban.
RolapitantThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Rolapitant.
SaquinavirThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Saquinavir.
SertralineSertraline may increase the anticoagulant activities of Dabigatran etexilate.
SimeprevirThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Simeprevir.
Sodium bicarbonateThe serum concentration of Dabigatran etexilate can be decreased when it is combined with Sodium bicarbonate.
StreptokinaseStreptokinase may increase the anticoagulant activities of Dabigatran etexilate.
SugammadexSugammadex may increase the anticoagulant activities of Dabigatran etexilate.
SulfinpyrazoneSulfinpyrazone may increase the anticoagulant activities of Dabigatran etexilate.
SulindacSulindac may increase the anticoagulant activities of Dabigatran etexilate.
SulodexideDabigatran etexilate may increase the anticoagulant activities of Sulodexide.
SunitinibThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Sunitinib.
TacrolimusThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Tacrolimus.
TamoxifenThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Tamoxifen.
TelaprevirThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Telaprevir.
TenecteplaseTenecteplase may increase the anticoagulant activities of Dabigatran etexilate.
TesmilifeneThe serum concentration of Dabigatran etexilate can be decreased when it is combined with Tesmilifene.
Tiaprofenic acidTiaprofenic acid may increase the anticoagulant activities of Dabigatran etexilate.
TiboloneTibolone may increase the anticoagulant activities of Dabigatran etexilate.
TicagrelorTicagrelor may increase the anticoagulant activities of Dabigatran etexilate.
TiclopidineTiclopidine may increase the anticoagulant activities of Dabigatran etexilate.
TinzaparinDabigatran etexilate may increase the anticoagulant activities of Tinzaparin.
TipranavirThe serum concentration of Dabigatran etexilate can be decreased when it is combined with Tipranavir.
TirofibanTirofiban may increase the anticoagulant activities of Dabigatran etexilate.
TolmetinTolmetin may increase the anticoagulant activities of Dabigatran etexilate.
TositumomabThe risk or severity of adverse effects can be increased when Dabigatran etexilate is combined with Tositumomab.
TreprostinilDabigatran etexilate may increase the anticoagulant activities of Treprostinil.
UrokinaseUrokinase may increase the anticoagulant activities of Dabigatran etexilate.
VandetanibThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Vandetanib.
VemurafenibThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Vemurafenib.
VenlafaxineVenlafaxine may increase the anticoagulant activities of Dabigatran etexilate.
VerapamilThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Verapamil.
VilazodoneVilazodone may increase the anticoagulant activities of Dabigatran etexilate.
VinblastineThe serum concentration of Dabigatran etexilate can be decreased when it is combined with Vinblastine.
Vitamin EVitamin E may increase the anticoagulant activities of Dabigatran etexilate.
VorapaxarThe risk or severity of adverse effects can be increased when Vorapaxar is combined with Dabigatran etexilate.
VortioxetineVortioxetine may increase the anticoagulant activities of Dabigatran etexilate.
WarfarinDabigatran etexilate may increase the anticoagulant activities of Warfarin.
Food Interactions
  • St. John's Wort

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Thrombospondin receptor activity
Specific Function:
Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing.
Gene Name:
F2
Uniprot ID:
P00734
Molecular Weight:
70036.295 Da
References
  1. Squizzato A, Dentali F, Steidl L, Ageno W: New direct thrombin inhibitors. Intern Emerg Med. 2009 Dec;4(6):479-84. doi: 10.1007/s11739-009-0314-8. Epub 2009 Sep 15. [PubMed:19756950 ]
  2. Liesenfeld KH, Schafer HG, Troconiz IF, Tillmann C, Eriksson BI, Stangier J: Effects of the direct thrombin inhibitor dabigatran on ex vivo coagulation time in orthopaedic surgery patients: a population model analysis. Br J Clin Pharmacol. 2006 Nov;62(5):527-37. [PubMed:17061960 ]
  3. Karthikeyan G, Eikelboom JW, Hirsh J: Dabigatran: ready for prime time? Pol Arch Med Wewn. 2010 Apr;120(4):137-42. [PubMed:20424539 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Triglyceride lipase activity
Specific Function:
Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acyl-CoA ester. Hydrolyzes the methyl ester group of cocaine to form benzoylecgonine. Catalyzes the transesterification of cocaine to form cocaethylene. Displays fatty acid ethyl ester synthase activity,...
Gene Name:
CES1
Uniprot ID:
P23141
Molecular Weight:
62520.62 Da
References
  1. Hu ZY, Parker RB, Herring VL, Laizure SC: Conventional liquid chromatography/triple quadrupole mass spectrometry based metabolite identification and semi-quantitative estimation approach in the investigation of in vitro dabigatran etexilate metabolism. Anal Bioanal Chem. 2013 Feb;405(5):1695-704. doi: 10.1007/s00216-012-6576-4. Epub 2012 Dec 14. [PubMed:23239178 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Methylumbelliferyl-acetate deacetylase activity
Specific Function:
Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Shows high catalytic efficiency for hydrolysis of cocaine, 4-methylumbelliferyl acetate, heroin and 6-monoacetylmorphine.
Gene Name:
CES2
Uniprot ID:
O00748
Molecular Weight:
61806.41 Da
References
  1. Hu ZY, Parker RB, Herring VL, Laizure SC: Conventional liquid chromatography/triple quadrupole mass spectrometry based metabolite identification and semi-quantitative estimation approach in the investigation of in vitro dabigatran etexilate metabolism. Anal Bioanal Chem. 2013 Feb;405(5):1695-704. doi: 10.1007/s00216-012-6576-4. Epub 2012 Dec 14. [PubMed:23239178 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Retinoic acid binding
Specific Function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 2 lacks transferase activity but acts as a negative regulator of isoform 1.
Gene Name:
UGT1A9
Uniprot ID:
O60656
Molecular Weight:
59940.495 Da
References
  1. Ebner T, Wagner K, Wienen W: Dabigatran acylglucuronide, the major human metabolite of dabigatran: in vitro formation, stability, and pharmacological activity. Drug Metab Dispos. 2010 Sep;38(9):1567-75. doi: 10.1124/dmd.110.033696. Epub 2010 Jun 15. [PubMed:20551237 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Glucuronosyltransferase activity
Specific Function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.Its unique specificity for 3,4-catechol estrogens and estriol suggests it may play an important role in regulating the level and activity of these potent and active estrogen metabolites. Is also active with androsterone, hyodeoxycholic acid and tetrachlorocatechol...
Gene Name:
UGT2B7
Uniprot ID:
P16662
Molecular Weight:
60694.12 Da
References
  1. Ebner T, Wagner K, Wienen W: Dabigatran acylglucuronide, the major human metabolite of dabigatran: in vitro formation, stability, and pharmacological activity. Drug Metab Dispos. 2010 Sep;38(9):1567-75. doi: 10.1124/dmd.110.033696. Epub 2010 Jun 15. [PubMed:20551237 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Glucuronosyltransferase activity
Specific Function:
UDPGTs are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isozyme displays activity toward several classes of xenobiotic substrates, including simple phenolic compounds, 7-hydroxylated coumarins, flavonoids, anthraquinones, and certain drugs and their hydroxylated metabolites. It also catalyzes the glucuronidatio...
Gene Name:
UGT2B15
Uniprot ID:
P54855
Molecular Weight:
61035.815 Da
References
  1. Ebner T, Wagner K, Wienen W: Dabigatran acylglucuronide, the major human metabolite of dabigatran: in vitro formation, stability, and pharmacological activity. Drug Metab Dispos. 2010 Sep;38(9):1567-75. doi: 10.1124/dmd.110.033696. Epub 2010 Jun 15. [PubMed:20551237 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Nadph dehydrogenase (quinone) activity
Specific Function:
The enzyme apparently serves as a quinone reductase in connection with conjugation reactions of hydroquinones involved in detoxification pathways as well as in biosynthetic processes such as the vitamin K-dependent gamma-carboxylation of glutamate residues in prothrombin synthesis.
Gene Name:
NQO2
Uniprot ID:
P16083
Molecular Weight:
25918.4 Da
References
  1. Michaelis S, Marais A, Schrey AK, Graebner OY, Schaudt C, Sefkow M, Kroll F, Dreger M, Glinski M, Koester H, Metternich R, Fischer JJ: Dabigatran and dabigatran ethyl ester: potent inhibitors of ribosyldihydronicotinamide dehydrogenase (NQO2). J Med Chem. 2012 Apr 26;55(8):3934-44. doi: 10.1021/jm3001339. Epub 2012 Apr 17. [PubMed:22494098 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
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
Molecular Weight:
141477.255 Da
References
  1. Galanis T, Thomson L, Palladino M, Merli GJ: New oral anticoagulants. J Thromb Thrombolysis. 2011 Apr;31(3):310-20. doi: 10.1007/s11239-011-0559-8. [PubMed:21327511 ]
  2. Scaglione F: New oral anticoagulants: comparative pharmacology with vitamin K antagonists. Clin Pharmacokinet. 2013 Feb;52(2):69-82. doi: 10.1007/s40262-012-0030-9. [PubMed:23292752 ]
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Drug created on May 03, 2010 12:25 / Updated on August 24, 2016 01:52