Details of Drug-Drug Interaction
| Drug General Information (ID: DDIDWAGP01) | |||||||||
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| Drug Name | Busulfan | Drug Info | Fosphenytoin | Drug Info | |||||
| Drug Type | Small molecule | Small molecule | |||||||
| Therapeutic Class | Antineoplastics | Anticonvulsants | |||||||
| Structure | |||||||||
| Mechanism of Busulfan-Fosphenytoin Interaction (Severity Level: Moderate) | |||||||||
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| Attenuated pharmacological effects (Unspecific) Click to Show/Hide Mechanism Graph | |||||||||
| Drug Name | Busulfan | Fosphenytoin | |||||||
| Mechanism | Glutathione-S-transferase substrate | Glutathione-S-transferase inducer | |||||||
| Key Mechanism Factor 1 | |||||||||
| Factor Name | Glutathione S-transferase A3 |
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Structure
Sequence
MAGKPKLHYFNGRGRMEPIRWLLAAAGVEFEEKFIGSAEDLGKLRNDGSLMFQQVPMVEIDGMKLVQTRAILNYIASKYNLYGKDIKERALIDMYTEGMADLNEMILLLPLCRPEEKDAKIALIKEKTKSRYFPAFEKVLQSHGQDYLVGNKLSRADISLVELLYYVEELDSSLISNFPLLKALKTRISNLPTVKKFLQPGSPRKPPADAKALEEARKIFRF
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| Gene Name | GSTA3 | ||||||||
| Uniprot ID | GSTA3_HUMAN | ||||||||
| KEGG Pathway | hsa:2940 | ||||||||
| Protein Family | GST superfamily, Alpha family | ||||||||
| Protein Function |
Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Catalyzes isomerization reactions that contribute to the biosynthesis of steroid hormones. Efficiently catalyze obligatory double-bond isomerizations of delta(5)-androstene-3,17-dione and delta(5)-pregnene-3,20-dione, precursors to testosterone and progesterone, respectively. Has substantial activity toward aflatoxin B1-8,9-epoxide (By similarity).
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| Mechanism Description |
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| Recommended Action | |||||||||
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| Management | Because busulfan crosses the blood brain barrier and may induce seizures, anticonvulsants are typically employed prophylactically when high-dose busulfan is given for myeloablative conditioning. Some manufacturers recommend that all patients receiving high-dose busulfan be premedicated with phenytoin, in which case the dosing may already have taken into account the interaction. Nevertheless, clinical and laboratory monitoring of patient response to busulfan and phenytoin should be performed. The same manufacturers further suggest that use of other anticonvulsants such as benzodiazepines may result in higher busulfan exposure, which may increase the risk of veno-occlusive disease, seizures, and other serious adverse effects. Therefore, plasma busulfan levels should be closely monitored, and patients observed for development of toxicity. By contrast, some manufacturers recommend using a benzodiazepine such as clonazepam, diazepam, or lorazepam rather than an enzyme-inducing anticonvulsant. | ||||||||