Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIKUWPYI6)
  Drug Name Sulfasalazine Drug Info Azathioprine Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antiinflammatory Agents Immunosuppressive Agents
  Structure

 Mechanism of Sulfasalazine-Azathioprine Interaction (Severity Level: Moderate)
     Non-CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Sulfasalazine Azathioprine
      Mechanism Thiopurine methyltransferase inhibitor Thiopurine methyltransferase substrate
      Key Mechanism Factor 1
Factor Name Thiopurine methyltransferase
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Structure Sequence
MDGTRTSLDIEEYSDTEVQKNQVLTLEEWQDKWVNGKTAFHQEQGHQLLKKHLDTFLKGKSGLRVFFPLCGKAVEMKWFADRGHSVVGVEISELGIQEFFTEQNLSYSEEPITEIPGTKVFKSSSGNISLYCCSIFDLPRTNIGKFDMIWDRGALVAINPGDRKCYADTMFSLLGKKFQYLLCVLSYDPTKHPGPPFYVPHAEIERLFGKICNIRCLEKVDAFEERHKSWGIDCLFEKLYLLTEK
Gene Name TPMT
Uniprot ID TPMT_HUMAN
KEGG Pathway hsa:7172
Protein Family Class I-like SAM-binding methyltransferase superfamily
Protein Function
Catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine (also called mercaptopurine, 6-MP or its brand name Purinethol) and 6-thioguanine (also called tioguanine or 6-TG) using S-adenosyl-L-methionine as the methyl donor (PubMed:657528, PubMed:18484748). TPMT activity modulates the cytotoxic effects of thiopurine prodrugs. A natural substrate for this enzyme has yet to be identified.
    Click to Show/Hide
      Mechanism Description
  • Decreased metabolism of Azathioprine caused by Sulfasalazine mediated inhibition of non-CYP450 enzyme

Recommended Action
      Management Caution is advised if aminosalicylate derivatives must be used concomitantly with purine antagonist antimetabolites. Patients receiving the combination should be closely monitored for hematologic toxicity, and the antimetabolite dosage adjusted accordingly.

References
1 Lewis LD, Benin A, Szumlanski CL, et al. "Olsalazine and 6-mercaptopurine-related bone marrow suppression: a possible drug-drug interaction." Clin Pharmacol Ther 62 (1997): 464-75. [PMID: 9357398]
2 Lewis LD, Benin A, Szumlanski CL, Otterness DM, Lennard L, Weinshilboum RM, Nierenberg DW "Olsalazine and 6-mercaptopurine-related bone marrow suppression: A possible drug-drug interaction (Vol 62, pg 464, 1997)." Clin Pharmacol Ther 67 (2000): 431. [PMID: 9357398]
3 Lowry PW, Franklin CL, Weaver AL, et al. "Leucopenia resulting from a drug interaction between azathioprine or 6-mercaptopurine and mesalamine, sulphasalazine, or balsalazide." Gut 49 (2001): 656-64. [PMID: 11600468]
4 Lowry PW, Szumlanski CL, Weinshilboum RM, Sandborn WJ "Balsalazide and azathiprine or 6-mercaptopurine: evidence for a potentially serious drug interaction [letter comment." Gastroenterology 116 (1999): 1505-6. [PMID: 10391741]
5 Product Information. Imuran (azathioprine). Glaxo Wellcome, Research Triangle Park, NC.
6 Product Information. Purinethol (mercaptopurine). Glaxo Wellcome, Research Triangle Pk, NC.
7 Product Information. Tabloid (thioguanine). Prasco Laboratories, Cincinnati, OH.
8 Szumlanski CL, Weinshilboum RM "Sulphasalazine inhibition of thiopurine methyltransferase: possible mechanism for interaction with 6-mercaptopurine and azathioprine." Br J Clin Pharmacol 39 (1995): 456-9. [PMID: 7640156]