THEODORE G. TONG, Pharm.D.; SUSAN M. POND, M.B., M.D.; MARY JEANNE KREEK, M.D.; NARGIS F. JAFFERY, Ph.D.; NEAL L. BENOWITZ, M.D.
TONG TG, POND SM, KREEK MJ, JAFFERY NF, BENOWITZ NL. Phenytoin-Induced Methadone Withdrawal. Ann Intern Med. 1981;94:349-351. doi: 10.7326/0003-4819-94-3-349
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Published: Ann Intern Med. 1981;94(3):349-351.
Methadone-maintained volunteers experienced moderately severe opiate withdrawal symptoms within 3 or 4 days of beginning phenytoin in therapeutic doses. The area under the methadone plasma concentration-time curve decreased while the ratio of the pyrrolidine-to-metabolite excretion in urine to this area increased significantly. This suggests that phenytoin accelerates methadone metabolism. Methadone dosing adjustments should be anticipated when phenytoin is initiated or discontinued in methadone-maintained patients.
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