Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDISUZX4Q1)
  Drug Name Digoxin Drug Info Itraconazole Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antiarrhythmic Agents Antifungal Agents
  Structure

 Mechanism of Digoxin-Itraconazole Interaction (Severity Level: Major)
     Transporter inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Digoxin Itraconazole
      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 Itraconazole 

Recommended Action
      Management Caution is advised when digoxin is administered with itraconazole. The prescribing information for digoxin recommends decreasing the dosage by approximately 30% to 50% or modifying the dosing frequency when initiating itraconazole, followed by continued therapeutic monitoring of digoxin. 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 Alderman CP, Allcroft PD "Digoxin-itraconazole interaction: possible mechanisms." Ann Pharmacother 31 (1997): 438-40. [PMID: 9101006]
2 Alderman CP, Jersmann HP "Digoxin-itraconazole interaction." Med J Aust 159 (1993): 838-9. [PMID: 8264497]
3 Balayssac D, Authier N, Cayre A, Coudore F "Does inhibition of P-glycoprotein lead to drug-drug interactions?" Toxicol Lett 156 (2005): 319-29. [PMID: 15763631]
4 Cone LA, Himelman RB, Hirschberg JN, Hutcheson JW "Itraconazole-related amaurosis and vomiting due to digoxin toxicity." West J Med 165 (1996): 322. [PMID: 8993214]
5 Drescher S, Glaeser H, Murdter T, Hitzl M, Eichelbaum M, Fromm MF "P-glycoprotein-mediated intestinal and biliary digoxin transport in humans." Clin Pharmacol Ther 73 (2003): 223-31. [PMID: 12621387]
6 Ito S, Koren G "Possible mechanism of digoxin-itraxonazole interaction." Ann Pharmacother 31 (1997): 1091-2. [PMID: 9296256]
7 Kauffman CA, Bagnasco FA "Digoxin toxicity associated with itraconazole therapy." Clin Infect Dis 15 (1992): 886-7. [PMID: 1332784]
8 Mathis AS, Friedman GS "Coadministration of digoxin with itraconazole in renal transplant recipients." Am J Kidney Dis 37 (2001): u101-8. [PMID: 11157404]
9 Mcclean KL, Sheehan GJ "Interaction between itraconazole and digoxin." Clin Infect Dis 18 (1994): 259-60. [PMID: 8161643]
10 Partanen J, Jalava KM, Neuvonen PJ "Itraconazole increases serum digoxin concentration." Pharmacol Toxicol 79 (1996): 274-6. [PMID: 8936563]
11 Rex J "Itraconazole-digoxin interaction." Ann Intern Med 116 (1992): 525. [PMID: 1310840]
12 Sachs MK, Blanchard LM, Green PJ "Interaction of itraconazole and digoxin." Clin Infect Dis 16 (1993): 400-3. [PMID: 8384010]