Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDISKOIUN3)
  Drug Name Varenicline Drug Info Vandetanib Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Smoking Cessation Agents Antineoplastics
  Structure

 Mechanism of Varenicline-Vandetanib Interaction (Severity Level: Moderate)
     Transporter inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Varenicline Vandetanib
      Mechanism OCT2 substrate OCT2 inhibitor
      Key Mechanism Factor 1
Factor Name Solute carrier family 22 member 2
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Structure Sequence
MPTTVDDVLEHGGEFHFFQKQMFFLLALLSATFAPIYVGIVFLGFTPDHRCRSPGVAELSLRCGWSPAEELNYTVPGPGPAGEASPRQCRRYEVDWNQSTFDCVDPLASLDTNRSRLPLGPCRDGWVYETPGSSIVTEFNLVCANSWMLDLFQSSVNVGFFIGSMSIGYIADRFGRKLCLLTTVLINAAAGVLMAISPTYTWMLIFRLIQGLVSKAGWLIGYILITEFVGRRYRRTVGIFYQVAYTVGLLVLAGVAYALPHWRWLQFTVSLPNFFFLLYYWCIPESPRWLISQNKNAEAMRIIKHIAKKNGKSLPASLQRLRLEEETGKKLNPSFLDLVRTPQIRKHTMILMYNWFTSSVLYQGLIMHMGLAGDNIYLDFFYSALVEFPAAFMIILTIDRIGRRYPWAASNMVAGAACLASVFIPGDLQWLKIIISCLGRMGITMAYEIVCLVNAELYPTFIRNLGVHICSSMCDIGGIITPFLVYRLTNIWLELPLMVFGVLGLVAGGLVLLLPETKGKALPETIEEAENMQRPRKNKEKMIYLQVQKLDIPLN
Gene Name 44836
Uniprot ID S22A2_HUMAN
KEGG Pathway hsa:6582
Protein Family Major facilitator (TC 2.A.1) superfamily
Protein Function
Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamine, creatinine, amantadine, memantine, acriflavine, 4-[4-(dimethylamino)-styryl]-N-methylpyridinium ASP, amiloride, metformin, N-1-methylnicotinamide (NMN), tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, cisplatin and oxaliplatin. Cisplatin may develop a nephrotoxic action. Transport of creatinine is inhibited by fluoroquinolones such as DX-619 and LVFX. This transporter is a major determinant of the anticancer activity of oxaliplatin and may contribute to antitumor specificity.
    Click to Show/Hide
      Mechanism Description
  • Decreased clearance of Varenicline due to the transporter inhibition by Vandetanib 

Recommended Action
      Management Caution is advised when vandetanib is used with drugs that are substrates of OCT2, particularly those with a narrow therapeutic range such as metformin. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever vandetanib is added to or withdrawn from therapy.

References
1 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
2 EMEA. European Medicines Agency "EPARs. European Union Public Assessment Reports.".
3 Product Information. Vandetanib (vandetanib). Astra-Zeneca Pharmaceuticals, Wilmington, DE.