Details of Drug-Drug Interaction
| Drug General Information (ID: DDITMACQ6E) | |||||||||
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| Drug Name | Rifabutin | Drug Info | Vortioxetine | Drug Info | |||||
| Drug Type | Small molecule | Small molecule | |||||||
| Therapeutic Class | Antibiotics | Antidepressants | |||||||
| Structure | |||||||||
| Mechanism of Rifabutin-Vortioxetine Interaction (Severity Level: Moderate) | |||||||||
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| CYP450 enzyme induction Click to Show/Hide Mechanism Graph | |||||||||
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| Drug Name | Rifabutin | Vortioxetine | |||||||
| Mechanism | CYP450 2D6 inducer | CYP450 2D6 substrate | |||||||
| Key Mechanism Factor 1 | |||||||||
| Factor Name | Cytochrome P450 2D6 |
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Structure
Sequence
MGLEALVPLAVIVAIFLLLVDLMHRRQRWAARYPPGPLPLPGLGNLLHVDFQNTPYCFDQLRRRFGDVFSLQLAWTPVVVLNGLAAVREALVTHGEDTADRPPVPITQILGFGPRSQGVFLARYGPAWREQRRFSVSTLRNLGLGKKSLEQWVTEEAACLCAAFANHSGRPFRPNGLLDKAVSNVIASLTCGRRFEYDDPRFLRLLDLAQEGLKEESGFLREVLNAVPVLLHIPALAGKVLRFQKAFLTQLDELLTEHRMTWDPAQPPRDLTEAFLAEMEKAKGNPESSFNDENLRIVVADLFSAGMVTTSTTLAWGLLLMILHPDVQRRVQQEIDDVIGQVRRPEMGDQAHMPYTTAVIHEVQRFGDIVPLGVTHMTSRDIEVQGFRIPKGTTLITNLSSVLKDEAVWEKPFRFHPEHFLDAQGHFVKPEAFLPFSAGRRACLGEPLARMELFLFFTSLLQHFSFSVPTGQPRPSHHGVFAFLVSPSPYELCAVPR
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| Gene Name | CYP2D6 | ||||||||
| Uniprot ID | CP2D6_HUMAN | ||||||||
| KEGG Pathway | hsa:1565 | ||||||||
| Protein Family | Cytochrome P450 family | ||||||||
| Protein Function |
A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). 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:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
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| Mechanism Description |
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| Recommended Action | |||||||||
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| Management | An increase in the dosage of vortioxetine should be considered when used in combination with potent CYP450 inducers (e.g., carbamazepine, phenobarbital, phenytoin, rifamycins) for greater than 14 days, up to a maximum of three times the original dosage depending on clinical response. Following discontinuation of the potent CYP450 inducer, vortioxetine dosage should be returned to the original level within 14 days. Other known CYP450 inducers include aminoglutethimide, barbiturates, bexarotene, bosentan, enzalutamide, efavirenz, etravirine, nevirapine, somatrem, somatropin, and various other anticonvulsants, although the extent to which they interact with vortioxetine is unknown. | ||||||||
| References | |||||||||||||||||||
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| 1 | Product Information. Brintellix (vortioxetine). Takeda Pharmaceuticals America, Lincolnshire, IL. | ||||||||||||||||||