Experts urge caution over paracetamol use as studies link common painkiller to multiple health risks

Leading researchers and practising clinicians are increasingly warning that paracetamol, the world’s most widely used painkiller, carries a wider range of risks than previously recognised and should not be used routinely for long periods.

The warnings follow a series of recent studies and reviews linking regular paracetamol (acetaminophen) use to acute liver failure, raised blood pressure, gastrointestinal bleeding, kidney damage, tinnitus and possible associations with neurodevelopmental conditions such as autism and ADHD. In England the NHS dispensed more than 15 million paracetamol prescriptions in 2024/25, with an estimated cost of £80.6 million, while market surveys suggest the average Briton takes roughly 70 tablets a year.

Professor Andrew Moore, of the Cochrane Collaboration’s Pain, Palliative Care and Supportive Care group, said the “conventional view” that paracetamol is a safe, default treatment for pain is likely incorrect. Writing in The Conversation, he summarised pooled evidence indicating associations between paracetamol use and increased rates of death, heart attack, stomach bleeding and kidney failure. General practitioners quoted in recent coverage echoed the concern, saying patients often treat paracetamol as harmless and may unknowingly exceed recommended doses.

Clinical and laboratory studies explain some of the drug’s risks. Paracetamol is normally metabolised by the liver; at therapeutic doses a toxic intermediate compound called NAPQI is detoxified by glutathione. At higher doses, or when dosing is sustained over several days, glutathione stores can be exhausted and NAPQI can damage liver cells. Published reports identify paracetamol as a leading cause of acute liver failure in adults, with toxicity in some people reported at doses approaching twice the recommended daily limit.

The dose commonly described as the maximum recommended daily amount is 4 grams — typically two 500 mg tablets taken up to four times in 24 hours. Clinicians warn that taking slightly more than this level on consecutive days, or combining paracetamol tablets with other products that contain the drug such as some cold and flu remedies, can lead to accidental overdose. The risk is higher among people who are underweight, consume alcohol regularly or have pre-existing liver disease.

Evidence about paracetamol’s effectiveness for chronic pain has also been questioned. Reviews cited by the UK’s National Institute for Health and Care Excellence (NICE) in 2020 found little or no benefit for conditions such as lower back pain and osteoarthritis and concluded paracetamol should not be routinely used for chronic pain because of limited efficacy and potential harms.

Several observational and interventional studies have examined cardiovascular effects. A 2022 randomised crossover study at the University of Edinburgh compared standard paracetamol dosing (two 500 mg tablets four times daily) with placebo in 110 people with treated hypertension and reported a measurable rise in blood pressure during the paracetamol period. Large epidemiological analyses in the United States have also reported an association between chronic paracetamol use and increased risk of hypertension in women. Researchers caution that mechanisms are not fully understood, but note that paracetamol may affect some of the same pain pathways as non-steroidal anti-inflammatory drugs (NSAIDs), which are known to raise blood pressure with prolonged use.

A recent US observational study reported an 18 percent increased risk of tinnitus among people who took daily paracetamol, though investigators emphasised that the design cannot prove causation and did not record precise dosing. The lead author recommended that people considering regular use of over-the-counter analgesics consult a health professional to weigh risks and benefits.

Several large population studies have also explored prenatal exposure. An analysis covering about 100,000 individuals reported an association between maternal paracetamol exposure during pregnancy and a higher likelihood of autism spectrum disorder and attention-deficit/hyperactivity disorder in children. Authors and outside experts emphasise these findings are observational, that exposure levels were not quantified precisely, and that unmeasured factors could explain part or all of the association. Further research is needed to determine whether the link is causal.

Older adults may face particular risks. A long-term study tracking roughly half a million people aged 65 and over for up to 20 years found higher rates of gastrointestinal bleeding, chronic kidney disease and other complications among those prescribed paracetamol. Even participants prescribed the drug twice within a six-month period showed increased risk for some adverse outcomes, and the most frequent users had the highest risks, including peptic ulcer complications and bleeding.

Regulatory and clinical guidance continues to recommend paracetamol as an option for short-term pain relief and fever reduction because it is effective for many people and has a lower gastrointestinal and bleeding risk than some alternatives. However, NHS and NICE advice underscores that anyone with cardiovascular disease, liver disease or other significant health issues should use the lowest effective dose for the shortest possible time and consult their clinician about safer alternatives or monitoring.

Clinicians interviewed say practical steps to reduce harm include checking all medications and cold remedies for hidden paracetamol content to avoid accidental doubling-up, avoiding alcohol while taking the drug, adhering to the 4 g daily limit for adults (and lower recommended limits for some groups), and seeking medical advice if pain is persistent and requires repeated dosing. Those at higher risk — including older adults, people with existing liver or kidney disease, and those who drink heavily — should discuss pain management plans with a clinician.

Researchers caution that while paracetamol remains useful for many short-term indications, the accumulating evidence highlights limits to its safety when used repeatedly or at high cumulative doses. They call for clearer public messaging about product contents, more detailed studies to clarify causal pathways for the associations reported, and renewed efforts to identify safer long-term pain-management strategies.