Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIJ0KDXZA)
  Drug Name Pirfenidone Drug Info Ceritinib Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Pulmonary Fibrosis Inhibitors Multikinase Inhibitors
  Structure

 Mechanism of Pirfenidone-Ceritinib Interaction (Severity Level: Moderate)
     CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Pirfenidone Ceritinib
      Mechanism CYP450 2E1 substrate CYP450 2E1 inhibitor
      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).
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      Mechanism Description
  • Decreased metabolism of Pirfenidone caused by Ceritinib mediated inhibition of CYP450 enzyme

Recommended Action
      Management Caution is advised if ceritinib is used concomitantly with drugs that are substrates of CYP450 2A6 and/or 2E1, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring should be considered whenever ceritinib is added to or withdrawn from therapy with these drugs. Patients should be monitored for the development of adverse effects.

References
1 Cerner Multum, Inc. "Australian Product Information.".
2 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
3 EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring.".