Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIJKAHU18)
  Drug Name Acetaminophen Drug Info Isoniazid Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Analgesics Antitubercular Agents
  Structure

 Mechanism of Acetaminophen-Isoniazid Interaction (Severity Level: Moderate)
     CYP450 enzyme induction Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Acetaminophen Isoniazid
      Mechanism 1 CYP450 2E1 substrate CYP450 2E1 inducer
      Key Mechanism Factor 1
Factor Name Cytochrome P450 2E1
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Structure Sequence
MSALGVTVALLVWAAFLLLVSMWRQVHSSWNLPPGPFPLPIIGNLFQLELKNIPKSFTRLAQRFGPVFTLYVGSQRMVVMHGYKAVKEALLDYKDEFSGRGDLPAFHAHRDRGIIFNNGPTWKDIRRFSLTTLRNYGMGKQGNESRIQREAHFLLEALRKTQGQPFDPTFLIGCAPCNVIADILFRKHFDYNDEKFLRLMYLFNENFHLLSTPWLQLYNNFPSFLHYLPGSHRKVIKNVAEVKEYVSERVKEHHQSLDPNCPRDLTDCLLVEMEKEKHSAERLYTMDGITVTVADLFFAGTETTSTTLRYGLLILMKYPEIEEKLHEEIDRVIGPSRIPAIKDRQEMPYMDAVVHEIQRFITLVPSNLPHEATRDTIFRGYLIPKGTVVVPTLDSVLYDNQEFPDPEKFKPEHFLNENGKFKYSDYFKPFSTGKRVCAGEGLARMELFLLLCAILQHFNLKPLVDPKDIDLSPIHIGFGCIPPRYKLCVIPRS
Gene Name CYP2E1
Uniprot ID CP2E1_HUMAN
KEGG Pathway hsa:1571
Protein Family Cytochrome P450 family
Protein Function
A cytochrome P450 monooxygenase involved in the metabolism of fatty acids (PubMed:10553002, PubMed:18577768). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10553002, PubMed:18577768). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates fatty acids specifically at the omega-1 position displaying the highest catalytic activity for saturated fatty acids (PubMed:10553002, PubMed:18577768). May be involved in the oxidative metabolism of xenobiotics (Probable).
    Click to Show/Hide
      Mechanism Description
  • Increased metabolism of Acetaminophen caused by Isoniazid mediated induction of CYP450 enzyme
     Increased risk of hepatotoxicity Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Acetaminophen Isoniazid
      Mechanism 2 Hepatotoxicity Hepatotoxicity
      Key Mechanism Factor 2
Factor Name Hepatotoxicity
Factor Description Combination of drugs that can induce hepatotoxicity may increase the risk of liver injury. Symptoms vary depending on the level of exposure and the total extent of liver damage, and may cause few symptoms if the damage is mild, and eventually lead to liver failure in patients with severe damage.
      Mechanism Description
  • Increased risk of hepatotoxicity by the combination of Acetaminophen and Isoniazid 

Recommended Action
      Management Until more information is available, concurrent acetaminophen use should be limited. Close attention should be paid to clinical and laboratory evidence of hepatotoxicity. Both drugs should be discontinued if evidence of hepatoxicity is observed. Aspirin or nonsteroidal inflammatory agents may be safer alternatives.

References
1 Crippin JS "Acetaminophen hepatotoxicity: potentiation by isoniazid." Am J Gastroenterol 88 (1993): 590-2. [PMID: 8470644]
2 Epstein MM, Nelson SD, Slattery JT, Kalhorn TF, Wall RA, Wright JM "Inhibition of the metabolism of paracetamol by isoniazid." Br J Clin Pharmacol 31 (1991): 139-42. [PMID: 2049229]
3 Moulding TS, Redeker AG, Kanel GC "Acetaminophen, isoniazid, and hepatic toxicity." Ann Intern Med 114 (1991): 431. [PMID: 1992890]
4 Murphy R, Swartz R, Watkins PB "Severe acetaminophen toxicity in a patient receiving isoniazid." Ann Intern Med 113 (1990): 799-800. [PMID: 2240884]
5 Nolan CM, Sandblom RE, Thummel KE, Slattery JT, Nelson SD "Hepatotoxicity associated with acetaminophen usage in patients receiving multiple drug therapy for tuberculosis." Chest 105 (1994): 408-11. [PMID: 7508362]