Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIBKPR3ZM)
  Drug Name Gemfibrozil Drug Info Eluxadoline Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antihyperammonia Agents Peripheral Opioid Receptor Mixed Agonists/Antagonists
  Structure

 Mechanism of Gemfibrozil-Eluxadoline Interaction (Severity Level: Major)
     Transporter inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Gemfibrozil Eluxadoline
      Mechanism OATP1B1 inhibitor OATP1B1 substrate
      Key Mechanism Factor 1
Factor Name Liver organic anion transporter 1
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Structure Sequence
MDQNQHLNKTAEAQPSENKKTRYCNGLKMFLAALSLSFIAKTLGAIIMKSSIIHIERRFEISSSLVGFIDGSFEIGNLLVIVFVSYFGSKLHRPKLIGIGCFIMGIGGVLTALPHFFMGYYRYSKETNINSSENSTSTLSTCLINQILSLNRASPEIVGKGCLKESGSYMWIYVFMGNMLRGIGETPIVPLGLSYIDDFAKEGHSSLYLGILNAIAMIGPIIGFTLGSLFSKMYVDIGYVDLSTIRITPTDSRWVGAWWLNFLVSGLFSIISSIPFFFLPQTPNKPQKERKASLSLHVLETNDEKDQTANLTNQGKNITKNVTGFFQSFKSILTNPLYVMFVLLTLLQVSSYIGAFTYVFKYVEQQYGQPSSKANILLGVITIPIFASGMFLGGYIIKKFKLNTVGIAKFSCFTAVMSLSFYLLYFFILCENKSVAGLTMTYDGNNPVTSHRDVPLSYCNSDCNCDESQWEPVCGNNGITYISPCLAGCKSSSGNKKPIVFYNCSCLEVTGLQNRNYSAHLGECPRDDACTRKFYFFVAIQVLNLFFSALGGTSHVMLIVKIVQPELKSLALGFHSMVIRALGGILAPIYFGALIDTTCIKWSTNNCGTRGSCRTYNSTSFSRVYLGLSSMLRVSSLVLYIILIYAMKKKYQEKDINASENGSVMDEANLESLNKNKHFVPSAGADSETHC
Gene Name OATP1B1
Uniprot ID SO1B1_HUMAN
KEGG Pathway hsa:10599
Protein Family Organo anion transporter (TC 2.A.60) family
Protein Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostaglandin E2, thromboxane B2, leukotriene C3, leukotriene E4, thyroxine and triiodothyronine. Involved in the clearance of bile acids and organic anions from the liver.
    Click to Show/Hide
      Mechanism Description
  • Decreased clearance of Eluxadoline due to the transporter inhibition by Gemfibrozil 

Recommended Action
      Management The recommended dosage of eluxadoline is 75 mg twice daily when used with OATP1B1 inhibitors. Patients should be monitored for adverse effects such as sedation, nausea, vomiting, constipation, abdominal pain, liver enzyme elevations, and pancreatitis.

References
1 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
2 Davenport JM, Covington P, Bonifacio L, McIntyre G, Venitz J "Effect of uptake transporters OAT3 and OATPIBI and efflux transporter MRP2 on the pharmacokinetics of eluxadoline." J Clin Pharmacol 55 (2015): 534-42. [PMID: 25491493]
3 Product Information. Viberzi (eluxadoline). Actavis Pharma, Inc., Parsippany, NJ.