Important Drug Interactions
Phenytoin and Methadone
67. B.D., a 32-year-old man, has an 18-year history of chronic pain in the right hip as a result of a motor vehicle accident. He has a long problem list that includes grand mal seizures and gastric ulcer disease. In the past, he has been treated with a variety of opioid analgesics on an as needed schedule, which resulted in escalating drug requirements and a complex regimen of multiple-ingredient drugs (e.g., Percocet, Tylenol #3, Vicodin). B.D.'s attending physician prescribed methadone 10 mg every 6 hours several weeks ago. This switch was initially very successful, but B.D. now presents with symptoms suggestive of opioid withdrawal and poor pain control despite good compliance to his methadone regimen. A note in his chart indicates that B.D. saw a neurologist recently who started him on phenytoin therapy. What important drug–drug interactions might explain this rather complex case?
Phenytoin (Dilantin) induces cytochrome P450 (CYP) 3A4 isoenzymes that are responsible for the clearance of methadone, and can thereby decrease serum concentrations of methadone and precipitate symptoms of withdrawal.226,227 The methadone dose should be increased to 20 mg every 6 hours, and a note should be made in the chart that the doses will need to be reduced if the phenytoin is discontinued for any reason. After his dose has been increased, B.D. should be watched closely for the next several days for drug-induced drowsiness because the long half-life of methadone can produce accumulation.
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