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15 May 1994 | Volume 120 Issue 10 | Pages 892-893
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persisted for several days after therapy with phenytoin was discontinued but that declined rapidly after ranitidine was withdrawn.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). LETTER
Phenytoin and Ranitidine Interaction
TO THE EDITOR:
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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.
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1. Skinner MH, Lenert L, Blaschke TF. Theophylline toxicity subsequent to ranitidine administration: a possible drug-drug interaction. Am J Med. 1989; 86:129-32.
2. Bramhall D, Levine M. Possible interaction of ranitidine with phenytoin. Drug Intell Clin Pharm. 1988; 22:979-80.
3. Gardner ME, Sikorski GW. Ranitidine and theophylline (Letter). Ann Intern Med. 1985; 102:559.
4. Tse CS, Akinwande KI, Biallowons K. Phenytoin concentration elevation subsequent to ranitidine administration. Ann Pharmacother. 1993; 27:1448-51.
5. Hoensch HP, Hutzel H, Kirch W, Ohnhaus EE. Isolation of human hepatic microsomes and their inhibition by cimetidine and ranitidine. Eur J Clin Pharmacol. 1985; 29:199-206.
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