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Cimetidine as adjunctive treatment for acetaminophen overdose

Rocky Mountain Poison and Drug Center, Denver General Hospital, Emergency Medicine Research Center, University of Colorado Health Sciences Center, Denver, Colorado 80204, The Milton S. Hershey Medical Center, Pennsylvania State University, Hershey, Pennsylvania 17033, USA

Nancy Janco

Rocky Mountain Poison and Drug Center, Denver General Hospital, Emergency Medicine Research Center, University of Colorado Health Sciences Center, Denver, Colorado 80204

Kenneth W Kulig

Rocky Mountain Poison and Drug Center, Denver General Hospital, Emergency Medicine Research Center, University of Colorado Health Sciences Center, Denver, Colorado 80204

Barry H Rumack

Rocky Mountain Poison and Drug Center, Denver General Hospital, Emergency Medicine Research Center, University of Colorado Health Sciences Center, Denver, Colorado 80204

The aim of this study was to determine if cimetidine in addition to N-acetylcysteine and standard supportive care provide additional hepatoprotection following acute acetaminophen poisoning.

It was designed as a prospective study with alternate month treatment protocol, and the work was carried out at a regional certified poison information centre.

For a 2-year period, consultations received by the Rocky Mountain Poison Center involving acute aceta minophen overdose patients with a serum level above the nomogram line, but who would not receive N-acetylcys tine therapy until at least 8 h postingestion, were prospec tively evaluated for adjunctive treatment with cimetidine. All patients received standard supportive therapy and N- acetylcysteine treatment. During odd numbered months, cimetidine 300 mg was administered intravenously every 6 h for the duration of N-acetylcysteine therapy.

Forty-one cimetidine treated patients were compared to 66 patients in the control group. The peak measured AST levels (+/- s.e.) were 1259+/-330 and 1301+/-451 for the control and cimetidine treatment groups, respectively (P = 0.94). Fourteen of 64 patients (21%) in the control group and 8/41 patients (20%) in the cimetidine group developed an AST > 1000 IUL^-1. There were no statistical differences between the cimetidine-treated and control groups when classified by AST<100IUL ^-1, 100- 1000IUL^-1, or >1000IUL^-1.

The addition of cimetidine therapy to standard N- acetylcysteine treatment did not provide additional hepatoprotection in acutely acetaminophen poisoned patients when treatment was started later than 8 h post overdose. Larger doses of cimetidine along with more fre quent or continuous intravenous administration may war rant further study.

Key Words: acetaminophen • cimetidine • poisoning • cytochrome P450 • hepatotoxicity

Human & Experimental Toxicology, Vol. 14, No. 3, 299-304 (1995)
DOI: 10.1177/096032719501400311


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