Details of Drug-Drug Interaction
| Drug General Information (ID: DDIU60XYEP) | |||||||||
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| Drug Name | Letrozole | Drug Info | Fedratinib | Drug Info | |||||
| Drug Type | Small molecule | Small molecule | |||||||
| Therapeutic Class | Antineoplastics | Multikinase Inhibitors | |||||||
| Structure | |||||||||
| Mechanism of Letrozole-Fedratinib Interaction (Severity Level: Moderate) | |||||||||
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| CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph | |||||||||
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| Drug Name | Letrozole | Fedratinib | |||||||
| Mechanism | CYP450 2C19 inhibitor | CYP450 2C19 substrate | |||||||
| Key Mechanism Factor 1 | |||||||||
| Factor Name | Cytochrome P450 2C19 |
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Structure
Sequence
MDPFVVLVLCLSCLLLLSIWRQSSGRGKLPPGPTPLPVIGNILQIDIKDVSKSLTNLSKIYGPVFTLYFGLERMVVLHGYEVVKEALIDLGEEFSGRGHFPLAERANRGFGIVFSNGKRWKEIRRFSLMTLRNFGMGKRSIEDRVQEEARCLVEELRKTKASPCDPTFILGCAPCNVICSIIFQKRFDYKDQQFLNLMEKLNENIRIVSTPWIQICNNFPTIIDYFPGTHNKLLKNLAFMESDILEKVKEHQESMDINNPRDFIDCFLIKMEKEKQNQQSEFTIENLVITAADLLGAGTETTSTTLRYALLLLLKHPEVTAKVQEEIERVIGRNRSPCMQDRGHMPYTDAVVHEVQRYIDLIPTSLPHAVTCDVKFRNYLIPKGTTILTSLTSVLHDNKEFPNPEMFDPRHFLDEGGNFKKSNYFMPFSAGKRICVGEGLARMELFLFLTFILQNFNLKSLIDPKDLDTTPVVNGFASVPPFYQLCFIPV
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| Gene Name | CYP2C19 | ||||||||
| Uniprot ID | CP2CJ_HUMAN | ||||||||
| KEGG Pathway | hsa:1557 | ||||||||
| Protein Family | Cytochrome P450 family | ||||||||
| Protein Function |
A cytochrome P450 monooxygenase involved in the metabolism of polyunsaturated fatty acids (PUFA) (PubMed:18577768, PubMed:19965576, PubMed:20972997). 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:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates PUFA specifically at the omega-1 position (PubMed:18577768). Catalyzes the epoxidation of double bonds of PUFA (PubMed:20972997, PubMed:19965576). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine. Hydroxylates fenbendazole at the 4' position (PubMed:23959307).
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| Mechanism Description |
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| Recommended Action | |||||||||
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| Management | Caution is recommended with the concomitant use of fedratinib and CYP450 2C19 inhibitors. Patients should be monitored for adverse effects including anemia, thrombocytopenia, diarrhea, nausea, vomiting, and liver (ALT, AST) and pancreatic (amylase, lipase) enzyme elevations. | ||||||||
| References | |||||||||||||||||||
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| 1 | Cerner Multum, Inc. "UK Summary of Product Characteristics.". | ||||||||||||||||||
| 2 | Product Information. Inrebic (fedratinib). Celgene Corporation, Summit, NJ. | ||||||||||||||||||