Alcohol and acetaminophen

http://www.ncbi.nlm.nih.gov/pubmed/21193765

As we mentioned earlier, the FDA’s 2010 revised warning labeling on APAP packaging addresses the risk of hepatotoxicity’s occurring when APAP is used with alcohol. The wording, included under a “liver warning,” states that consuming three or more alcoholic drinks daily while taking APAP could result in “severe liver injury.”18

As both APAP and alcohol are potentially hepatotoxic, excessive use or abuse of alcohol combined with the use of APAP could have a damaging effect on the liver. This is due to the fact that alcohol abuse could deplete liver stores of glutathione, which is needed for the metabolism of the hepatotoxin NAPQI.35

The FDA’s warning that consuming alcohol in conjunction with APAP could enhance the hepatotoxic effects of APAP, however, has not been supported by the literature. Attempts to link alcohol and APAP to the development of liver disease have revealed characteristics and behaviors that are common in the population that tends to use both alcohol and APAP. For example, regular alcohol users were more likely to use APAP. People who abuse alcohol were more likely to take excessive amounts of APAP and often took an APAP product that contained ethyl alcohol (for example, Vicks NyQuil, Procter & Gamble, Cincinnati).13,36 When tested in clinical studies, the administration of APAP to participants with alcoholism did not lead to the development of abnormal liver enzyme levels indicative of liver injury.35,37

The most definitive findings that cast a doubt on the effect of alcohol on the hepatotoxicity of APAP were reported by investigators of a study involving 362 patients who were admitted to an emergency department within 24 hours of an overdose of APAP. Among these patients, 178 (49 percent) also had consumed alcohol within four hours of taking APAP. All of the patients met the criteria for acute APAP toxicity and received the NAC antidote regimen.38 After the investigators conducted laboratory tests for hepatotoxicity, they found that only 5 percent of the alcohol users had evidence of liver damage compared with 15 percent of the nonusers. They concluded that coingestion of alcohol with an overdose of APAP may have provided a “protective effect.”38 This effect and its biochemical explanation have been recognized since the 1980s in literature reviews based on human and experimental animal studies.39 The hypothesis is that if alcohol has been consumed and is in the patient’s blood circulation at the time of the APAP overdose, the alcohol competes with the activity of the cytochrome P450 enzymes, thus reducing the formation of NAPQI.38

The increased risk of developing liver failure after an APAP overdose in both alcohol and APAP users may not be related to either APAP or alcohol. Several investigators have determined that regular users of both alcohol and APAP were more likely to postpone seeking emergency care than were occasional users, which would have delayed the administration of NAC within the critical time frame.13,36,38 This behavior could increase the rate of development of hepatotoxicity, as well as the number of patients who developed acute liver failure, thus further confounding the validity of the APAP-alcohol interaction.

A number of other variables may affect a patient’s susceptibility to the hepatotoxic effects of APAP when it is combined with alcohol. For example, Tsukamoto40 estimated that as few as 10 percent of alcohol abusers develop alcoholic cirrhosis. This susceptibility or resistance to liver disease probably is influenced by a number of genetic and environmental factors that act independently or synergistically.40 The wide range of the liver’s response to the effects of alcohol also is demonstrated by data from liver transplant recipients with cirrhosis who resumed drinking.41,42 Results from these follow-up studies showed a recurrence of alcoholic cirrhosis in 5 percent or fewer of these liver transplant recipients in the United States and Europe. Similar patient variability may apply to the effects of APAP.19 Examples of factors that may determine whether a drug is hepatotoxic include older age, female sex, malnutrition, concurrent use of other drugs, genetics and coexisting medical conditions.19

Given the FDA’s warning, the widespread use of APAP and the probability that patients who abuse alcohol also may abuse APAP, it would be prudent for dental practitioners to include a question about alcohol use in each patient’s medical history. The National Institute on Alcohol Abuse and Alcoholism has developed a single-question test that may be more acceptable to patients than are the older, multiple-question alcohol use screening instruments. The National Institute on Alcohol Abuse and Alcoholism’s single-question test asks, “How many times in the past year have you had five or more drinks (for men) or four or more drinks (for women) in a single day?”43 A response of one or more times is considered to indicate “unhealthy alcohol use.” If alcohol abuse is suspected, clinicians should caution the patient to avoid consuming alcohol during the period of APAP use.