November 8, 1999 -- Paracetamol, at a therapeutic dose of up to 4000 mg/day, does not cause liver toxicity, even in severe alcohol abusers given the drug at the period of peak susceptibility, according to the results of a new study by Professor Richard Dart, Director of the Rocky Mountain Poison and Drug Center, Denver, Colorado, USA.
Professor Dart presented preliminary results from the study, a systematic review of available evidence at the 'Clinical Consensus -- An International Update on Paracetamol' symposium held today in Sydney, Australia. He introduced the study, one of the most thorough investigations conducted to date, by putting the problem in context: "Paracetamol is one of the most commonly used OTC analgesics and alcohol is the most commonly used drug, therefore a large number of alcoholic patients are likely to be treated with paracetamol," said Professor Dart. "Sporadic reports have suggested in the past that there may be a relationship between chronic alcohol use and liver injury following paracetamol ingestion. We wanted to establish the true picture by looking at the strength of the available evidence."
The strongest evidence examined -- randomised controlled trials -- indicated that therapeutic dosing of paracetamol to the alcoholic patient was not associated with fulminant hepatic failure. In fact, there was no change at all in hepatic aminotransferase enzymes, prothrombin time or other biochemical parameters when compared to placebo groups.
Other evidence examined included retrospective case reviews and case reports. Although these data were numerous, the results were mixed and contradictory and cannot always be relied on. Professor Dart suggests that this could be due to inaccuracy of patient history, meaning that overdoses went undetected. For example, in some cases serum paracetamol was markedly elevated but the patient only admitted to having ingested doses within the therapeutic range of 4 g/day. The new study, in contrast, provide some of the best evidence yet.
Professor Dart concluded: "The evidence available does not support the contention that alcoholism increases liver injury following ingestion of paracetamol. Unless stronger evidence of a potentially dangerous interaction emerges, current therapeutic recommendations for use of paracetamol in conditions producing pain or fever should not be altered. Indeed, alternative pain relievers are likely to be more dangerous in the alcoholic patient."