Regular paracetamol use can cause severe complications in over-65s, researchers warn

15th January 2025

Repeated doses of paracetamol in older patients can lead to an increased risk of several severe complications, researchers have reported.

An analysis of 20 years of GP data found an increased risk of gastrointestinal, cardiovascular and renal complications associated with regular use of the painkiller.

The researchers from the University of Nottingham said the findings highlighted that care must be taken when used regularly for chronic conditions such as osteoarthritis.

Analysis of health records from 180,483 people over the age of 65 years who had been prescribed paracetamol repeatedly (≥2 prescriptions within six months) and 402,478 controls of the same age found an increased risk of peptic ulcers, heart failure, hypertension and chronic kidney disease.

The study also identified a dose-response relationship for paracetamol use and perforation or ulceration or bleeding, uncomplicated peptic ulcers, and chronic renal failure.

That pattern was the same when researchers only looked at the patients who had taken paracetamol, they reported.

It is also difficult to calculate exposure when most people take paracetamol episodically or for multiple reasons, they added.

A subgroup analysis focusing on patients with osteoarthritis also aligned with the overall findings, the researchers reported in the journal Arthritis Care and Research.

The team did note they could not account for paracetamol bought over the counter which is why they focused on those who would have received free prescriptions.

Study leader Professor Weiya Zhang from the NIHR Nottingham Biomedical Research Centre and professor of epidemiology, Faculty of Medicine & Health Sciences at the University of Nottingham, said to its perceived safety that paracetamol has long been recommended as the first-line drug treatment for osteoarthritis by many treatment guidelines, especially in older people who are at higher risk of drug-related complications. 

Yet their findings further challenge ‘whether acetaminophen [paracetamol] should be retained as the first-line oral analgesic’, especially in older people for common chronic painful conditions, given its non-clinically meaningful benefits and potential harms, he concluded.

It also supports recommendations by NICE to not prescribe paracetamol for osteoarthritis, he added.

‘Whilst further research is now needed to confirm our findings, given its minimal pain-relief effect, the use of paracetamol as a first line pain killer for long-term conditions such as osteoarthritis in older people needs to be carefully considered.’

A version of this article was originally published by our sister publication Pulse.

Study finds paracetamol use increases systolic blood pressure

23rd June 2022

Regular paracetamol use in both normotensive and hypertensive patients has been found to increase systolic but not diastolic blood pressure

Paracetamol use over a period of only two to three weeks seems to be enough to produce a significant increase in systolic blood pressure in normotensive and hypertensive patients according to the findings of a meta-analysis by researchers from New York, US.

Paracetamol (acetaminophen) is a widely for its analgesic and anti-pyretic properties and is considered to be generally safe unless taken in large quantities at which point, liver toxicity can occur. Though it is well established that non-steroidal anti-inflammatory drugs (NSAIDs), increase blood pressure in patients with controlled-hypertension, much less is known about the effect of paracetamol use on blood pressure.

Currently, some evidence suggests that paracetamol use, particularly, the effervescent form, is responsible for a significant daytime and overall increase in ambulatory 24 hour systolic blood pressure. However, in contrast, a review of the use of intravenous paracetamol, it was concluded that the drug actually has a hypotensive effect.

Moreover, this hypotensive effect has been shown in a study of 160 patients, to necessitate a therapeutic intervention in 34.9% of participants. While in a study of over 2,000 nursing home residents, paracetamol use was found to be safe for most, this was not the case for all residents.

With conflicting results, for the present analysis, the US team performed a systematic review and meta-analysis to investigate the effect of paracetamol use compared to placebo on systolic and diastolic ambulatory blood pressure.

They undertook a search of three major databases (PubMed, EMBASE and the Cochrane Library records) for randomised, controlled trials that included patients with or without cardiovascular disease and where changes in both systolic and diastolic pressure changes were reported.

Paracetamol use and changes in blood pressure

The search revealed only 3 relevant studies that included a total of 172 patients with a mean age of 59.9 years (73% male) and in which paracetamol was given daily over the course of two to three weeks.

Overall, paracetamol use resulted in a significantly higher systolic blood pressure compared to placebo (standardised mean difference, SMD = 0.35, 95% CI 0.08 – 0.63, p = 0.01). In a subgroup analysis of hypertensive patients, this difference was also significant (SMD = 0.38, 95% CI 0.05 – 0.71, p = 0.02).

Interestingly, there was no significant effect on diastolic blood pressure either overall (SMD = 0.18, 95% CI – 0.09 to 0.45, p = 0.19) or in the subgroup of hypertensive patients(SMD = 0.09, 95% CI -0.34 to 0.52, p = 0.68).

The authors suggested that while there is an underlying assumption that paracetamol use is generally safe, these findings challenge that assumption.

They concluded that there was a significant correlation between the use of paracetamol and systolic blood pressure in both normotensive and hypertensive patients.

Citation
Gupta R et al. Effect of acetaminophen on blood pressure: a systematic review and meta-analysis of randomized controlled trials Eur J Prev Cardiol 2022