Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDI26ZUSK0)
  Drug Name Digoxin Drug Info Dexlansoprazole Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antiarrhythmic Agents Proton Pump Inhibitors
  Structure

 Mechanism of Digoxin-Dexlansoprazole Interaction (Severity Level: Moderate)
     Altered gastric pH Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Digoxin Dexlansoprazole
      Mechanism 1 Gastric alkalinizer Gastric pH sensitive
      Key Mechanism Factor 1
Factor Name Gastric pH
Factor Description The normal pH range of gastric acid is between 1.5 and 3.5 and is highly acidic, consisting mainly of hydrochloric acid. Changes in the pH of the stomach can alter the absorption of drugs.
      Mechanism Description
  • Decreased absorption of Dexlansoprazole due to altered gastric pH caused by Digoxin 
     Transporter inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Digoxin Dexlansoprazole
      Mechanism 2 P-gp substrate P-gp inhibitor
      Key Mechanism Factor 2
Factor Name P-glycoprotein 1
×
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 Dexlansoprazole 
     Increased risk of hypomagnesemia Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Digoxin Dexlansoprazole
      Mechanism 3 Hypomagnesemia Hypomagnesemia
      Key Mechanism Factor 3
Factor Name Hypomagnesemia
Factor Description Hypomagnesemia is a condition that occurs when you have too much magnesium in your body. Symptoms of hypomagnesemia include: nausea, vomiting, neurological damage, abnormally low blood pressure (hypotension), flushing, and headaches.
      Mechanism Description
  • Increased risk of hypomagnesemia by the combination of Digoxin and Dexlansoprazole 

Recommended Action
      Management Caution is advised if digoxin is prescribed in combination with PPIs. Pharmacologic response and serum digoxin levels should be monitored more closely following the addition or discontinuation of PPI therapy, and the digoxin dosage adjusted as necessary. Patients should be advised to notify their physician if they experience potential signs and symptoms of digoxin toxicity such as nausea, anorexia, visual disturbances, slow pulse, or irregular heartbeats. Monitoring of serum magnesium levels is recommended prior to initiation of PPI therapy and periodically thereafter if prolonged treatment is anticipated or when combined with other agents that can cause hypomagnesemia (e.g., diuretics, aminoglycosides, cation exchange resins, amphotericin B, cetuximab, cisplatin, cyclosporine, foscarnet, panitumumab, pentamidine, tacrolimus). Patients should be advised to seek immediate medical attention if they develop potential signs and symptoms of hypomagnesemia such as palpitations, arrhythmia, muscle spasm, tremor, or convulsions. In children, abnormal heart rates may cause fatigue, upset stomach, dizziness, and lightheadedness. Magnesium replacement as well as discontinuation of the PPI may be required in some patients.

References
1 Andersson T "Omeprazole drug interaction studies." Clin Pharmacokinet 21 (1991): 195-212. [PMID: 1764870]
2 Kiley CA, Cragin DJ, Roth BJ "Omeprazole-associated digoxin toxicity." South Med J 100 (2007): 400-2. [PMID: 17458401]
3 Le GH, Schaefer MG, Plowman BK, et al. "Assessment of potential digoxin-rabeprazole interaction after formulary conversion of proton-pump inhibitors." Am J Health Syst Pharm 60 (2003): 1343-5. [PMID: 12901036]
4 Oosterhuis B, Jonkman JH, Andersson T, Zuiderwijk PB, Jedema JN "Minor effect of multiple dose omeprazole on the pharmacokinetics of digoxin after a single oral dose." Br J Clin Pharmacol 32 (1991): 569-72. [PMID: 1954072]
5 Product Information. Aciphex (rabeprazole) Janssen Pharmaceuticals, Titusville, NJ.
6 Product Information. Kapidex (dexlansoprazole). Takeda Pharmaceuticals America, Lincolnshire, IL.
7 Product Information. Nexium (esomeprazole) Astra-Zeneca Pharmaceuticals, Wilmington, DE.
8 Product Information. Prevacid (lansoprazole). TAP Pharmaceuticals Inc, Deerfield, IL.
9 Product Information. Prilosec (omeprazole). Merck & Co, Inc, West Point, PA.
10 Product Information. Protonix (pantoprazole) Wyeth-Ayerst Laboratories, Philadelphia, PA.
11 FDA. U.S. Food and Drug Administration "FDA Drug Safety Communication: Low magnesium levels can be associated with long-term use of proton pump inhibitor drugs (PPIs).".