Drug General Information (ID: DDIFB5CMPK)
  Drug Name Digoxin Drug Info Glecaprevir Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antiarrhythmic Agents Antiviral Agents
  Structure

 Mechanism of Digoxin-Glecaprevir Interaction (Severity Level: Moderate)
     Transporter inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Digoxin Glecaprevir
      Mechanism P-gp substrate P-gp inhibitor
      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 Digoxin due to the transporter inhibition by Glecaprevir 

Recommended Action
      Management Serum digoxin levels and pharmacologic effects should be closely monitored following the addition or withdrawal of glecaprevir-pibrentasvir. The manufacturer recommends measuring serum digoxin levels before initiating glecaprevir-pibrentasvir and reducing the levels by decreasing the digoxin dose approximately 50% or by modifying the dosing frequency, followed by continued monitoring. Patients should be advised to seek medical attention if they experience signs of digoxin toxicity such as nausea, anorexia, visual disturbances, slow pulse, or irregular heartbeat.

References
1 Darcy PF "Nutrient-drug interactions." Adverse Drug React Toxicol Rev 14 (1995): 233-54. [PMID: 8845456]
2 Product Information. Mavyret (glecaprevir-pibrentasvir). Abbott Pharmaceutical, Abbott Park, IL.