Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIX9RK58A)
  Drug Name Ribavirin Drug Info Azathioprine Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antiviral Agents Immunosuppressive Agents
  Structure

 Mechanism of Ribavirin-Azathioprine Interaction (Severity Level: Major)
     Non-CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Ribavirin Azathioprine
      Mechanism Inosine monophosphate dehydrogenase inhibitor Inosine monophosphate dehydrogenase substrate
      Key Mechanism Factor 1
Factor Name Inosine-5'-monophosphate dehydrogenase 1
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Structure Sequence
MADYLISGGTGYVPEDGLTAQQLFASADGLTYNDFLILPGFIDFIADEVDLTSALTRKITLKTPLISSPMDTVTEADMAIAMALMGGIGFIHHNCTPEFQANEVRKVKKFEQGFITDPVVLSPSHTVGDVLEAKMRHGFSGIPITETGTMGSKLVGIVTSRDIDFLAEKDHTTLLSEVMTPRIELVVAPAGVTLKEANEILQRSKKGKLPIVNDCDELVAIIARTDLKKNRDYPLASKDSQKQLLCGAAVGTREDDKYRLDLLTQAGVDVIVLDSSQGNSVYQIAMVHYIKQKYPHLQVIGGNVVTAAQAKNLIDAGVDGLRVGMGCGSICITQEVMACGRPQGTAVYKVAEYARRFGVPIIADGGIQTVGHVVKALALGASTVMMGSLLAATTEAPGEYFFSDGVRLKKYRGMGSLDAMEKSSSSQKRYFSEGDKVKIAQGVSGSIQDKGSIQKFVPYLIAGIQHGCQDIGARSLSVLRSMMYSGELKFEKRTMSAQIEGGVHGLHSYEKRLY
Gene Name IMPDH1
Uniprot ID IMDH1_HUMAN
KEGG Pathway hsa:3614
Protein Family IMPDH/GMPR family
Protein Function
Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth. Could also have a single-stranded nucleic acid-binding activity and could play a role in RNA and/or DNA metabolism. It may also have a role in the development of malignancy and the growth progression of some tumors.
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      Mechanism Description
  • Decreased metabolism of Azathioprine caused by Ribavirin mediated inhibition of non-CYP450 enzyme

Recommended Action
      Management The use of ribavirin in combination with 6-mercaptopurine or azathioprine should generally be avoided if possible. Patients receiving the combination should have complete blood counts, including platelet counts, monitored weekly for the first month, twice monthly for the second and third months, then monthly or more frequently if dosage or other therapy changes are necessary. Treatment with these medications should be discontinued promptly if pancytopenia develops, and the combination should not be reintroduced following recovery.

References
1 Canadian Pharmacists Association.
2 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
3 Chaparro M, Trapero-Marugan M, Moreno-Otero R, Gisbert JP "Azathioprine plus ribavirin treatment and pancytopenia." Aliment Pharmacol Ther 30 (2009): 962-3. [PMID: 19807727]
4 Peyrin-Biroulet L, Cadranel JF, Nousbaum JB, et al. "Interaction of ribavirin with azathioprine metabolism potentially induces myelosuppression." Aliment Pharmacol Ther 28 (2008): 984-93. [PMID: 18657132]
5 Product Information. Copegus (ribavirin). Roche Laboratories, Nutley, NJ.
6 Thevenot T, Mathurin P, Moussalli J, Perrin M, Plassart F, Blot C, Opolon P, Poynard T "Effects of cirrhosis, interferon and azathioprine on adverse events in patients with chronic hepatitis C treated with ribavirin." J Viral Hepat 4 (1997): 243-53. [PMID: 9278222]