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Phenytoin and Ranitidine Interaction
- C. S. Ted Tse, PharmD; and
- Peter Iagmin, MD
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TO THE EDITOR:
We report a rare case of elevated phenytoin plasma concentration associated with the concurrent use of ranitidine that persisted for several days after therapy with phenytoin was discontinued but that declined rapidly after ranitidine was withdrawn.
A 77-year-old African-American man with a 1-year history of severe stroke and residual right hemiparesis had entered our hospice for a new-onset seizure 4 weeks before this hospitalization. He was treated with phenytoin, 100 mg orally three times daily, and was discharged 1 week later with oral phenytoin suspension, 300 mg three times daily. Ranitidine, 150 mg orally twice daily, was added 5 days later. The patient returned because of abdominal pain; a plasma phenytoin level done the morning after his admission was 43 µg/mL (normal, 10 to 20 µg/mL). Therapy with phenytoin was discontinued, but plasma concentrations remained high after 1 week (Table 1).
The patient's other medications included acetaminophen and codeine elixir (12.5 mL orally every 4 hours as necessary) and acetaminophen suppositories (650 mg rectally every 4 hours as necessary). The patient had a normal serum creatinine level of 1.2 mg/dL (normal, 0.5 to 1.4 mg/dL) but a low serum albumin level of 20 g/L (normal, 35 to 52 g/L). Because we suspected that therapy with ranitidine might be inhibiting the metabolism of phenytoin, it was discontinued on day 8. The plasma phenytoin concentration then declined.
Other case reports in the literature have described the interference of ranitidine with the hepatic metabolism of other drugs [1-4]. The probable mechanism is binding to cytochrome P-450 hepatic mixed-function oxidase, as with other histamine-2 receptor antagonists [5].
We postulate that a small subset of patients may be susceptible to this effect. Patients using ranitidine and phenytoin concurrently should be routinely monitored.
C. S. Ted Tse, PharmD
Peter Iagmin, MD
St. James Hospital and Health Centers; Chicago Heights, IL 60411
The Editors welcome submissions for possible publication in the Letters section. Authors of letters should:
•Include no more than 300 words of text, three authors, and five references
•Type with double-spacing
•Send three copies of the letter, an authors' form signed by all authors, and a cover letter describing any conflicts of interest related to the contents of the letter.
Letters commenting on an Annals article will be considered if they are received within 6 weeks of the time the article was published. Only some of the letters received can be published. Published letters are edited and may be shortened; tables and figures are included only selectively. Authors will be notified that the letter has been received. If the letter is selected for publication, the author will be notified about 3 weeks before the publication date. Unpublished letters cannot be returned.
Annals welcomes electronically submitted letters.
- Copyright ©2004 by the American College of Physicians
