Details of Drug Interaction | MecDDI

Drug General Information (ID: DDIAUN6WR7)
Drug Name			Allopurinol		Drug Info		Azathioprine		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Antimetabolites				Immunosuppressive Agents
Structure

Mechanism of Allopurinol-Azathioprine Interaction (Severity Level: Major)
Non-CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph

Drug Name		Allopurinol				Azathioprine
Mechanism		Xanthine oxidase inhibitor				Xanthine oxidase substrate
Key Mechanism Factor 1
		Factor Name		Xanthine dehydrogenase/oxidase				× Structure Sequence MTADKLVFFVNGRKVVEKNADPETTLLAYLRRKLGLSGTKLGCGEGGCGACTVMLSKYDRLQNKIVHFSANACLAPICSLHHVAVTTVEGIGSTKTRLHPVQERIAKSHGSQCGFCTPGIVMSMYTLLRNQPEPTMEEIENAFQGNLCRCTGYRPILQGFRTFARDGGCCGGDGNNPNCCMNQKKDHSVSLSPSLFKPEEFTPLDPTQEPIFPPELLRLKDTPRKQLRFEGERVTWIQASTLKELLDLKAQHPDAKLVVGNTEIGIEMKFKNMLFPMIVCPAWIPELNSVEHGPDGISFGAACPLSIVEKTLVDAVAKLPAQKTEVFRGVLEQLRWFAGKQVKSVASVGGNIITASPISDLNPVFMASGAKLTLVSRGTRRTVQMDHTFFPGYRKTLLSPEEILLSIEIPYSREGEYFSAFKQASRREDDIAKVTSGMRVLFKPGTTEVQELALCYGGMANRTISALKTTQRQLSKLWKEELLQDVCAGLAEELHLPPDAPGGMVDFRCTLTLSFFFKFYLTVLQKLGQENLEDKCGKLDPTFASATLLFQKDPPADVQLFQEVPKGQSEEDMVGRPLPHLAADMQASGEAVYCDDIPRYENELSLRLVTSTRAHAKIKSIDTSEAKKVPGFVCFISADDVPGSNITGICNDETVFAKDKVTCVGHIIGAVVADTPEHTQRAAQGVKITYEELPAIITIEDAIKNNSFYGPELKIEKGDLKKGFSEADNVVSGEIYIGGQEHFYLETHCTIAVPKGEAGEMELFVSTQNTMKTQSFVAKMLGVPANRIVVRVKRMGGGFGGKETRSTVVSTAVALAAYKTGRPVRCMLDRDEDMLITGGRHPFLARYKVGFMKTGTVVALEVDHFSNVGNTQDLSQSIMERALFHMDNCYKIPNIRGTGRLCKTNLPSNTAFRGFGGPQGMLIAECWMSEVAVTCGMPAEEVRRKNLYKEGDLTHFNQKLEGFTLPRCWEECLASSQYHARKSEVDKFNKENCWKKRGLCIIPTKFGISFTVPFLNQAGALLHVYTDGSVLLTHGGTEMGQGLHTKMVQVASRALKIPTSKIYISETSTNTVPNTSPTAASVSADLNGQAVYAACQTILKRLEPYKKKNPSGSWEDWVTAAYMDTVSLSATGFYRTPNLGYSFETNSGNPFHYFSYGVACSEVEIDCLTGDHKNLRTDIVMDVGSSLNPAIDIGQVEGAFVQGLGLFTLEELHYSPEGSLHTRGPSTYKIPAFGSIPIEFRVSLLRDCPNKKAIYASKAVGEPPLFLAASIFFAIKDAIRAARAQHTGNNVKELFRLDSPATPEKIRNACVDKFTTLCVTGVPENCKPWSVRV
		Gene Name		XDH
		Uniprot ID		XDH_HUMAN
		KEGG Pathway		hsa:7498
		Protein Family		Xanthine dehydrogenase family
		Protein Function		Key enzyme in purine degradation. Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species. Has also low oxidase activity towards aldehydes (in vitro). Click to Show/Hide
Mechanism Description		Decreased metabolism of Azathioprine caused by Allopurinol mediated inhibition of non-CYP450 enzyme

Recommended Action
Management		Caution is advised if allopurinol must be used concomitantly with oral thiopurines. Most authorities recommend that thiopurine dosage be reduced to approximately 1/4 to 1/3 the usual dosage, and the patient closely monitored for hematologic and other toxicity. Subsequent doses should be adjusted based on therapeutic response and appearance of adverse effects. Patients should be advised to consult their physician if they develop signs and symptoms suggestive of thiopurine toxicity such as fever, chills, sore throat, fatigue, lethargy, pallor, anorexia, jaundice, dark urine, nausea, vomiting, signs of local infection, and unusual bleeding or bruising.

References
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12	Product Information. Imuran (azathioprine). Glaxo Wellcome, Research Triangle Park, NC.
13	Product Information. Purinethol (mercaptopurine). Glaxo Wellcome, Research Triangle Pk, NC.
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