Supporting safe use of paracetamol

There is anecdotal evidence that liver toxicity can occur when therapeutic doses of paracetamol (4 g per day) are used in adults with intrahepatic glutathione depletion. Intrahepatic glutathione depletion can occur in people who are malnourished, cachectic or frail, or have alcoholism or decompensated cirrhosis. Liver toxicity is more likely when more than one of these conditions is present. Although cautious dosing is often advised in these people, there is a lack of consistent clinical evidence to support dose reduction. Dose reduction can be considered for complex patients (eg patients with decompensated cirrhosis or multiple conditions associated with glutathione depletion) but should not be undertaken routinely—expert advice may be needed. Inappropriate dose reductions can result in inadequate analgesia and, consequently, use of more harmful analgesics. For further advice on paracetamol use and dosing in adults with cirrhosis, see Tips for prescribing analgesics for patients with cirrhosis.