GI/Hepatology Express Report

Publication date: 2002-04-04

Acetaminophen and Alcohol: Understanding the Latest Evidence-Based Medicine on Acetaminophen Use in Patients Who Drink Alcohol

This report was reviewed for medical and scientific accuracy by Kiron M. Das, MD, PhD, FRCP, FACP, Professor of Medicine, Molecular Genetics and Microbiology; Chief, Division of Gastroenterology/Hepatology, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, New Jersey

Editorial

Edwin K. Kuffner Jr., MD, Attending Toxicologist, Rocky Mountain Poison and Drug Center, Denver, Colorado, Instructor, School of Pharmacy, University of Colorado Health Sciences Center, Denver, Colorado

For more than 50 years in the United States (U.S.), acetaminophen has demonstrated a remarkable safety profile in virtually all patient populations when used appropriately at therapeutic doses. Despite this safety profile, there has been concern for many years among healthcare providers about the safety of therapeutic doses of acetaminophen being used by alcoholic patients and patients who drink alcohol regularly.¹ Many clinicians practicing today do not realize that the concerns regarding alcohol and acetaminophen use are largely theoretical and not supported by current standards of evidence-based medicine.

Epidemiological concerns are related to the patterns of use and availability of both alcohol and acetaminophen. Acetaminophen, the most commonly recommended over-the-counter (OTC) analgesic and antipyretic is used by millions of Americans every day. In fact, in any given week, approximately 20% of adults in the U. S. will have taken some form of acetaminophen.² Alcohol is without question the most commonly used and abused drug in the U.S. with a lifetime risk for alcoholism in the U.S. between 5-10% and with approximately 60% of Americans drinking alcohol regularly, the public health consequences of an alcohol-acetaminophen drug-drug interaction are staggering.³

Pharmacological concerns are primarily related to the cytochrome P450 system, specifically CYP2E1, which is only involved in the metabolism of both acetaminophen and alcohol to a minor extent. The small amount of acetaminophen that is metabolized by CYP2E1 is converted to a toxic metabolite, n-acetyl-p-benzoquinoneimine (NAPQI). Following a therapeutic dose of acetaminophen, hepatic stores of glutathione easily detoxify the small amount of the toxic metabolite that is formed. Since chronic alcohol use can induce CYP2E1, it has been theorized that alcoholics and patients who drink alcohol regularly metabolize a greater percentage of acetaminophen via this otherwise minor pathway, generate more of the toxic metabolite (NAPQI), overwhelm the hepatic stores of glutathione, and develop hepatotoxicity. Although this is a compelling theory, the majority of pharmacokinetic and clinical studies conducted in humans do not support it.^4-8

Since theoretical concerns regarding the use of therapeutic doses of acetaminophen in alcoholic patients and patients who drink alcohol regularly continues to be a topic of interest amongst healthcare providers, we recently conducted two studies at the Rocky Mountain Poison and Drug Center aimed at answering the question: Can alcoholic patients develop hepatotoxicity from therapeutic doses of acetaminophen?

Discussed in this GI/Hepatology Express Report are the results of these two studies that have been recently published.

The first study is a systematic review of recent English literature between 1996 and 1999, which identified only 20 reports involving 25 patients containing enough information to even consider the possibility that an alcoholic patient who ingested less than or equal to 4 grams of acetaminophen per day would develop hepatotoxicity.⁹ Common weaknesses of these case reports included retrospective data collection that was often incomplete, suspected inaccuracies in the alcoholic patient's