Busulfan oral/injection and Phenytoin Extended-Release Capsules
Determining the interaction of Busulfan oral/injection and Phenytoin Extended-Release Capsules and the possibility of their joint administration.
In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.
Consumer:Phenytoin may reduce the blood levels of busulfan in some patients. It is unclear whether this will alter the effectiveness of busulfan. You may need a dose adjustment or more frequent monitoring by your doctor to safely use both medications. Talk to your doctor if you have any questions or concerns. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.
Professional:MONITOR: Limited data suggest that coadministration with phenytoin may decrease the plasma concentrations of busulfan. The proposed mechanism is phenytoin induction of busulfan conjugation via glutathione-S-transferase. A study in seven patients receiving oral busulfan (1 mg/kg four times daily for 4 days) for myeloablative conditioning prior to bone marrow transplantation and phenytoin for seizure prophylaxis found that busulfan elimination half-life decreased by 23%, clearance increased by 19%, and systemic exposure (AUC) decreased by 16% between the first and last dose of busulfan. There was also a continuous decrease in the steady-state level of busulfan in four of the patients. By contrast, no changes in busulfan pharmacokinetics were observed in 10 patients who received diazepam for seizure prophylaxis. Another study reported an approximately 21% increase in busulfan oral clearance associated with phenytoin use in a group of 64 adults and 12 children receiving busulfan conditioning. In a study of mice given a lethal dose of busulfan, a significantly greater proportion survived if they were pretreated with phenytoin or phenobarbital, presumably due to reduced busulfan exposure. However, not all published data support an interaction. One group of investigators studied busulfan clearance in 24 patients receiving intravenous busulfan with clonazepam and found no significant change in clearance when compared to historical data collected for 127 patients treated with phenytoin.
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.
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- Carreras E, Cahn JY, Puozzo C, et al. "Influence on Busilvex pharmacokinetics of clonazepam compared to previous phenytoin historical data." Anticancer Res 30 (2010): 2977-84
- Fitzsimmons WE, Ghalie R, Kaizer H "The effect of hepatic enzyme inducers on busulfan neurotoxicity and myelotoxicity." Cancer Chemother Pharmacol 27 (1990): 226-8
- "Product Information. Myleran (busulfan)." Prasco Laboratories, Cincinnati, OH.
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- "Product Information. Busulfex (busulfan)." ESP Pharma Inc, Edison, NJ.
Generic Name: busulfan
Brand name: Busulfex, Myleran
Synonyms: Busulfan (oral/injection), Busulfan
Generic Name: phenytoin
Brand name: Dilantin, Phenytek, Dilantin Infatabs, Phenytoin Sodium, Prompt
Synonyms: Phenytoin
In the course of checking the drug compatibility and interactions, data from the following reference sources was used: Drugs.com, Rxlist.com, Webmd.com, Medscape.com.
- Busulfan oral/injection-Phenytoin Infatabs
- Busulfan oral/injection-Phenytoin injection
- Busulfan oral/injection-Phenytoin Intravenous
- Busulfan oral/injection-Phenytoin Oral Suspension
- Busulfan oral/injection-Phenytoin Sodium
- Busulfan oral/injection-Phenytoin Sodium, Prompt injection
- Phenytoin Extended-Release Capsules-Busulfan Tablet
- Phenytoin Extended-Release Capsules-Busulfex
- Phenytoin Extended-Release Capsules-Butabarbital
- Phenytoin Extended-Release Capsules-Butalbital and Acetaminophen
- Phenytoin Extended-Release Capsules-Butalbital and Acetaminophen Capsule
- Phenytoin Extended-Release Capsules-Butalbital Compound