Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIOGTXRHA)
  Drug Name Carvedilol Drug Info Edoxaban Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Vasodilator Agents Anticoagulants/Factor Xa Inhibitors
  Structure

 Mechanism of Carvedilol-Edoxaban Interaction (Severity Level: Major)
     Transporter inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Carvedilol Edoxaban
      Mechanism P-gp inhibitor P-gp substrate
      Key Mechanism Factor 1
Factor Name P-glycoprotein 1
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Structure Sequence
MDLEGDRNGGAKKKNFFKLNNKSEKDKKEKKPTVSVFSMFRYSNWLDKLYMVVGTLAAIIHGAGLPLMMLVFGEMTDIFANAGNLEDLMSNITNRSDINDTGFFMNLEEDMTRYAYYYSGIGAGVLVAAYIQVSFWCLAAGRQIHKIRKQFFHAIMRQEIGWFDVHDVGELNTRLTDDVSKINEGIGDKIGMFFQSMATFFTGFIVGFTRGWKLTLVILAISPVLGLSAAVWAKILSSFTDKELLAYAKAGAVAEEVLAAIRTVIAFGGQKKELERYNKNLEEAKRIGIKKAITANISIGAAFLLIYASYALAFWYGTTLVLSGEYSIGQVLTVFFSVLIGAFSVGQASPSIEAFANARGAAYEIFKIIDNKPSIDSYSKSGHKPDNIKGNLEFRNVHFSYPSRKEVKILKGLNLKVQSGQTVALVGNSGCGKSTTVQLMQRLYDPTEGMVSVDGQDIRTINVRFLREIIGVVSQEPVLFATTIAENIRYGRENVTMDEIEKAVKEANAYDFIMKLPHKFDTLVGERGAQLSGGQKQRIAIARALVRNPKILLLDEATSALDTESEAVVQVALDKARKGRTTIVIAHRLSTVRNADVIAGFDDGVIVEKGNHDELMKEKGIYFKLVTMQTAGNEVELENAADESKSEIDALEMSSNDSRSSLIRKRSTRRSVRGSQAQDRKLSTKEALDESIPPVSFWRIMKLNLTEWPYFVVGVFCAIINGGLQPAFAIIFSKIIGVFTRIDDPETKRQNSNLFSLLFLALGIISFITFFLQGFTFGKAGEILTKRLRYMVFRSMLRQDVSWFDDPKNTTGALTTRLANDAAQVKGAIGSRLAVITQNIANLGTGIIISFIYGWQLTLLLLAIVPIIAIAGVVEMKMLSGQALKDKKELEGSGKIATEAIENFRTVVSLTQEQKFEHMYAQSLQVPYRNSLRKAHIFGITFSFTQAMMYFSYAGCFRFGAYLVAHKLMSFEDVLLVFSAVVFGAMAVGQVSSFAPDYAKAKISAAHIIMIIEKTPLIDSYSTEGLMPNTLEGNVTFGEVVFNYPTRPDIPVLQGLSLEVKKGQTLALVGSSGCGKSTVVQLLERFYDPLAGKVLLDGKEIKRLNVQWLRAHLGIVSQEPILFDCSIAENIAYGDNSRVVSQEEIVRAAKEANIHAFIESLPNKYSTKVGDKGTQLSGGQKQRIAIARALVRQPHILLLDEATSALDTESEKVVQEALDKAREGRTCIVIAHRLSTIQNADLIVVFQNGRVKEHGTHQQLLAQKGIYFSMVSVQAGTKRQ
Gene Name ABCB1
Uniprot ID MDR1_HUMAN
KEGG Pathway hsa:5243
Protein Family ABC transporter superfamily
Protein Function
Translocates drugs and phospholipids across the membrane (PubMed:8898203, PubMed:2897240, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:9038218).
    Click to Show/Hide
      Mechanism Description
  • Decreased clearance of Edoxaban due to the transporter inhibition by Carvedilol 

Recommended Action
      Management When used for the treatment of deep vein thrombosis and pulmonary embolism, the manufacturer recommends that edoxaban dosage be reduced to 30 mg once daily in patients receiving concomitant treatment with certain P-gp inhibitors including azithromycin, clarithromycin, erythromycin, oral itraconazole, oral ketoconazole, quinidine, and verapamil. This dosage recommendation is based on data from a clinical study, the Hokusai VTE study, and is limited to use with the specific P-gp inhibitors mentioned.

References
1 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
2 Mendell J, Zahir H, Matsushima N, et al. "Drug-Drug Interaction Studies of Cardiovascular Drugs Involving P-Glycoprotein, an Efflux Transporter, on the Pharmacokinetics of Edoxaban, an Oral Factor Xa Inhibitor." Am J Cardiovasc Drugs (2013):. [PMID: 23784266]
3 Parasrampuria DA, Mendell J, Shi M, Matsushima N, Zahir H, Truitt K "Edoxaban drug-drug interactions with ketoconazole, erythromycin, and cyclosporine." Br J Clin Pharmacol 0 (2016): epub. [PMID: 27530188]
4 Product Information. Savaysa (edoxaban). Daiichi Sankyo, Inc., Parsippany, NJ.