Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDI58DGYEU)
  Drug Name Trifluridine Drug Info Zidovudine Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antiviral Agents Anti-Hiv Agents
  Structure

 Mechanism of Trifluridine-Zidovudine Interaction (Severity Level: Moderate)
     Competitive inhibition of metabolic enzyme Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Trifluridine Zidovudine
      Mechanism Thymidine kinase substrate Thymidine kinase substrate
      Key Mechanism Factor 1
Factor Name Thymidine kinase, cytosolic
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Structure Sequence
MSCINLPTVLPGSPSKTRGQIQVILGPMFSGKSTELMRRVRRFQIAQYKCLVIKYAKDTRYSSSFCTHDRNTMEALPACLLRDVAQEALGVAVIGIDEGQFFPDIVEFCEAMANAGKTVIVAALDGTFQRKPFGAILNLVPLAESVVKLTAVCMECFREAAYTKRLGTEKEVEVIGGADKYHSVCRLCYFKKASGQPAGPDNKENCPVPGKPGEAVAARKLFAPQQILQCSPAN
Gene Name TK1
Uniprot ID KITH_HUMAN
KEGG Pathway hsa:7083
Protein Family Thymidine kinase family
Protein Function
Cell-cycle-regulated enzyme of importance in nucleotide metabolism (PubMed:9575153). Catalyzes the first enzymatic step in the salvage pathway converting thymidine into thymidine monophosphate (PubMed:22385435). Transcriptional regulation limits expression to the S phase of the cell cycle and transient expression coincides with the oscillation in the intracellular dTTP concentration (Probable). Also important for the activation of anticancer and antiviral nucleoside analog prodrugs such as 1-b-d-arabinofuranosylcytosine (AraC) and 3c-azido-3c-deoxythymidine (AZT) (PubMed:22385435).
    Click to Show/Hide
      Mechanism Description
  • Increased plasma concentrations of Trifluridine and Zidovudine due to competitive inhibition of the same metabolic pathway

Recommended Action
      Management Caution is advised if trifluridine is used concomitantly with drugs that are substrates of thymidine kinase. Patients should be monitored for loss of therapeutic efficacy. If the concomitant drug is an antiviral medication, patients should be monitored for loss of antiviral efficacy and an alternative antiviral agent that is not a thymidine kinase substrate, such as lamivudine, zalcitabine, didanosine and/or abacavir should be considered.

References
1 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
2 Product Information. Lonsurf (tipiracil-trifluridine). Taiho Oncology, Inc., Princeton, NJ.
3 Product Information. Retrovir (zidovudine). Glaxo Wellcome, Research Triangle Park, NC.