Details of Drug-Drug Interaction
| Drug General Information (ID: DDI3WKMJUH) | |||||||||
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| Drug Name | Phenytoin | Drug Info | Brivaracetam | Drug Info | |||||
| Drug Type | Small molecule | Small molecule | |||||||
| Therapeutic Class | Anticonvulsants | Anticonvulsants | |||||||
| Structure | |||||||||
| Mechanism of Phenytoin-Brivaracetam Interaction (Severity Level: Moderate) | |||||||||
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| CYP450 enzyme induction Click to Show/Hide Mechanism Graph | |||||||||
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| Drug Name | Phenytoin | Brivaracetam | |||||||
| Mechanism | CYP450 2C19 inducer | 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 | The potential for diminished pharmacologic effects of brivaracetam should be considered during coadministration with potent CYP450 enzyme inducers. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate whenever a CYP450 inducer is added to or withdrawn from therapy. For patients receiving concomitant carbamazepine or phenytoin therapy, blood levels should be monitored following initiation or discontinuation of brivaracetam. Dosage reductions for carbamazepine and phenytoin may be required if tolerability issues arise. | ||||||||