Researchers found chronic users of paracetamol may increase their risk of death, or kidney, intestinal and heart problems.
Doctors may be underestimating the risks to patients from long-term use of paracetamol, the world's most popular painkiller.
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Researchers found chronic users of the drug - people who typically take large, daily doses over several years - may increase their risk of death, or kidney, intestinal and heart problems.
Led by Philip Conaghan at the Leeds Institute of Rheumatic and Musculoskeletal Medicine in northern England, the team analysed data from eight previously published studies into long-term paracetamol use.
The data came only from people who had paracetamol prescribed by a doctor, as opposed to over-the-counter purchases.
Two of the eight studies had found an increased risk of mortality, up to 63 per cent, among long-term paracetamol users, compared to those who had not been prescribed the drug during the study period.
Four found a heightened risk, ranging from 19 to 68 per cent, of cardiovascular problems. The risk of gastro-intestinal bleeding and other intestinal side-effects was up to 49 per cent as high.
Three studies found an adverse effect on kidneys.
In all cases, the risk was dose-dependent - in other words, the higher the dose, the greater the risk, said the analysis published in the British journal Annals of the Rheumatic Diseases.
Even though the risk in absolute terms was small, doctors should think carefully when prescribing the drug, it warned.
But other experts cautioned against over-reaction.
They pointed out the analysis was unable to tell whether early death and health problems were caused by an underlying illness rather than from the paracetamol.
Nor did it take into account over-the-counter purchases of the drug, a picture that could be far more complex.
"Paracetamol remains the safest analgesic (painkiller) available, and this study should not stop people taking it," said Nick Bateman, a professor of clinical toxicology at the University of Edinburgh in Scotland.
"Based on these results, the lowest effective dose for the shortest necessary period is advised," he told Britain's Science Media Centre.
"This is common sense for all medicines."
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