Details of Drug-Drug Interaction
| Drug General Information (ID: DDIA41ILUD) | |||||||||
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| Drug Name | Deferasirox | Drug Info | Pirfenidone | Drug Info | |||||
| Drug Type | Small molecule | Small molecule | |||||||
| Therapeutic Class | Chelating Agents | Pulmonary Fibrosis Inhibitors | |||||||
| Structure | |||||||||
| Mechanism of Deferasirox-Pirfenidone Interaction (Severity Level: Moderate) | |||||||||
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| CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph | |||||||||
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| Drug Name | Deferasirox | Pirfenidone | |||||||
| Mechanism | CYP450 1A2 inhibitor | CYP450 1A2 substrate | |||||||
| Key Mechanism Factor 1 | |||||||||
| Factor Name | Cytochrome P450 1A2 |
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Structure
Sequence
MALSQSVPFSATELLLASAIFCLVFWVLKGLRPRVPKGLKSPPEPWGWPLLGHVLTLGKNPHLALSRMSQRYGDVLQIRIGSTPVLVLSRLDTIRQALVRQGDDFKGRPDLYTSTLITDGQSLTFSTDSGPVWAARRRLAQNALNTFSIASDPASSSSCYLEEHVSKEAKALISRLQELMAGPGHFDPYNQVVVSVANVIGAMCFGQHFPESSDEMLSLVKNTHEFVETASSGNPLDFFPILRYLPNPALQRFKAFNQRFLWFLQKTVQEHYQDFDKNSVRDITGALFKHSKKGPRASGNLIPQEKIVNLVNDIFGAGFDTVTTAISWSLMYLVTKPEIQRKIQKELDTVIGRERRPRLSDRPQLPYLEAFILETFRHSSFLPFTIPHSTTRDTTLNGFYIPKKCCVFVNQWQVNHDPELWEDPSEFRPERFLTADGTAINKPLSEKMMLFGMGKRRCIGEVLAKWEIFLFLAILLQQLEFSVPPGVKVDLTPIYGLTMKHARCEHVQARLRFSIN
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| Gene Name | CYP1A2 | ||||||||
| Uniprot ID | CP1A2_HUMAN | ||||||||
| KEGG Pathway | hsa:1544 | ||||||||
| Protein Family | Cytochrome P450 family | ||||||||
| Protein Function |
A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:9435160, PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576). 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:9435160, PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:11555828, PubMed:12865317). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2 (PubMed:11555828, PubMed:12865317). Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). May act as a major enzyme for all-trans retinoic acid biosynthesis in the liver. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). Primarily catalyzes stereoselective epoxidation of the last double bond of polyunsaturated fatty acids (PUFA), displaying a strong preference for the (R,S) stereoisomer (PubMed:19965576). Catalyzes bisallylic hydroxylation and omega-1 hydroxylation of PUFA (PubMed:9435160). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195). Plays a role in the oxidative metabolism of xenobiotics. Catalyzes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin (PubMed:14725854). Metabolizes caffeine via N3-demethylation (Probable).
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| Mechanism Description |
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| Recommended Action | |||||||||
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| Management | Caution is advised when pirfenidone is used concomitantly with CYP450 1A2 inhibitors. Patients should be closely monitored for adverse reactions such as hepatotoxicity, photosensitivity, rash, nausea, diarrhea, vomiting and dyspepsia, and consideration be given to dosage reduction, brief interruption, or permanent discontinuation of pirfenidone if clinically necessary in accordance with the product labeling. Coadministration of pirfenidone with CYP450 1A2 inhibitors in addition to inhibitors of other CYP450 isoenzymes involved in the metabolism of pirfenidone should be avoided, including significant inhibitors of CYP450 2C9 (e.g., amiodarone, fluconazole, imatinib, gemfibrozil, miconazole), 2C19 (e.g., chloramphenicol, cimetidine, esomeprazole, fluconazole, lansoprazole, omeprazole), and/or 2D6 (e.g., bupropion, cinacalcet, fluoxetine, paroxetine, quinidine, terbinafine). | ||||||||
| References | |||||||||||||||||||
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| 1 | Cerner Multum, Inc. "UK Summary of Product Characteristics.". | ||||||||||||||||||
| 2 | Product Information. Esbriet (pirfenidone). Intermune Inc, Brisbane, CA. | ||||||||||||||||||