Paracetamol may help protect against kidney damage in patients with malaria, according to a study recently published in Clinical Infectious Diseases.
The study found that for patients with severe malaria caused by the malaria parasite Plasmodium knowlesi (the most common cause of malaria in Malaysia), taking paracetamol regularly for 3 days led to improvements in kidney function when tested one week later.
The findings are important because they will help provide the best possible treatment to patients with severe malaria, said study leader Dr Daniel Cooper.
“Even minor kidney injury can have long-term effects, so anything we can do to minimise kidney injury from malaria will be beneficial for these patients’ long-term outcomes,” Dr Cooper said.
In collaboration with international partners, the study involved 396 people with knowlesi malaria in Sabah, Malaysia.
Assistant Professor Bridget Barber said that in severe malaria, red blood cells can rupture, releasing haemoglobin which can have a toxic impact on kidneys, and it is now believed that paracetamol can help to mitigate these toxic effects.
“These results are consistent with other studies conducted in patients with other forms of malaria, including in adults in Bangladesh, and in children in Africa. Importantly, these findings also suggest that paracetamol may help to protect the kidneys in other conditions that are also associated with rupture of red blood cells,” A/Prof Barber said.
Clinicians have recommended avoiding effervescent, soluble paracetamol that contains sodium, following findings from a large study that shows a link with a significantly increased risk of cardiovascular disease (CVD) and mortality in people who have hypertension and even in people with normal blood pressure.
Sodium is often used to help drugs such as paracetamol dissolve and disintegrate in water. However, effervescent and soluble formulations of 0.5g tablets of paracetamol can contain 0.44 and 0.39g of sodium respectively. If a person took the maximum daily dose of two 0.5g tablets every six hours, they would consume 3.5 and 3.1g of sodium respectively – a dose that exceeds the WHO-recommended total daily intake of 2g a day. In 2018, 170 people per 10 000 of the population in the UK were using sodium-containing medications, with a higher proportion among women. There are alternative formulations that contain little or no sodium.
Excessive salt in the diet remains a major public health problem and is associated with an increased risk of cardiovascular disease (CVD) and death among patients with hypertension. However, there is inconsistent evidence showing an increased risk in normotensive individuals.
Professor Chao Zeng led a team which analysed data from a medical database of UK GPs’ records. They looked at 4532 hypertensive patients who had been prescribed sodium-containing paracetamol and compared them with 146 866 hypertensive patients who had been prescribed sodium-free paracetamol. They also compared 5351 normotensive patients who were prescribed sodium-containing paracetamol with 141 948 normotensive patients prescribed sodium-free paracetamol. The patients were aged 60-90 years and followed up for one year.
The researchers found the risk of heart attack, stroke or heart failure after one year for patients with high blood pressure taking sodium-containing paracetamol was 5.6% (122 cases of CVD), while it was 4.6% (3051 CVD cases) among those taking sodium-free paracetamol. Mortality risk was also higher; the one-year risk was 7.6% (404 deaths) and 6.1% (5510 deaths), respectively.
A similar increased risk was seen among normotensive patients. Among those taking sodium-containing paracetamol, the one-year CVD risk was 4.4% (105 cases of CVD) and 3.7% (2079 cases of CVD) among those taking sodium-free containing paracetamol. The risk of dying was 7.3% (517 deaths) and 5.9% (5190 deaths), respectively.
Prof Zeng said: “We also found that the risk of cardiovascular disease and death increased as the duration of sodium-containing paracetamol intake increased. The risk of cardiovascular disease increased by a quarter for patients with high blood pressure who had one prescription of sodium-containing paracetamol, and it increased by nearly a half for patients who had five or more prescriptions of sodium-containing paracetamol. We saw similar increases in people without high blood pressure. The risk of death also increased with increasing doses of sodium-containing paracetamol in both patients with and without high blood pressure.”
Prof. Zeng said that clinicians and patients should be aware of the risks associated with sodium-containing paracetamol and avoid unnecessary consumption, especially when the medication is taken for a long period of time.
“Given that the pain relief effect of non-sodium-containing paracetamol is similar to that of sodium-containing paracetamol, clinicians may prescribe non-sodium-containing paracetamol to their patients to minimise the risk of cardiovascular disease and death. People should pay attention not only to salt intake in their food but also not overlook hidden salt intake from the medication in their cabinet,” he said.
“Although the US Food and Drug Administration requires that all over-the-counter medications should label the sodium content, no warning has been issued about the potentially detrimental effect of sodium-containing paracetamol on the risks of hypertension, cardiovascular disease and death. Our results suggest re-visiting the safety profile of effervescent and soluble paracetamol.”
Being an observational study it can only show only that there is an association between salt in paracetamol and CVD and deaths, rather than that salt causes these events. Other limitations include a lack of data on dietary intake of salt and excretion of salt from urinary samples. The use of over-the-counter paracetamol was not also recorded, however by restricting the study to those over 60 who qualify for free prescriptions in the UK, the risk of this is minimised.
Long-term paracetamol use could increase the risk of heart disease and strokes in people with high blood pressure, according to a randomised clinical trial by the University of Edinburgh.
Researchers recommend that patients with a long term prescription, usually for chronic pain, should rather choose the lowest effective dose for the shortest possible time.
The study, which appears in Circulation, is the first large randomised clinical trial to address the question of paracetamol’s effect on cardiovascular disease, and complements earlier work in observational studies.
In the latest study, 110 patients with a history of high blood pressure were prescribed one gram of paracetamol four times a day – a routinely prescribed dose in patients with chronic pain – or a matched placebo for two weeks. All patients received both treatments, with the order randomised and blinded. The paracetamol group saw a significant increase in blood pressure, compared to the placebo group.
This rise was similar to that seen with NSAIDs, and could be expected to increase the risk of heart disease or stroke by around 20%. The findings should lead to a review of long-term paracetamol prescriptions to patients, said the researchers, especially to those with hypertension and an increased risk of heart disease or stroke.
Lead Investigator Dr. Iain MacIntyre said: “This is not about short-term use of paracetamol for headaches or fever, which is, of course, fine—but it does indicate a newly discovered risk for people who take it regularly over the longer term, usually for chronic pain.”
Principal Investigator Professor David Webb said: “We would recommend that clinicians start with a low dose of paracetamol, and increase the dose in stages, going no higher than needed to control pain. Given the substantial rises in blood pressure seen in some of our patients, there may be a benefit for clinicians to keep a closer eye on blood pressure in people with high blood pressure who newly start paracetamol for chronic pain.”
Professor Sir Nilesh Samani, Medical Director at the British Heart Foundation, who funded the study, said: “This research shows how quickly regular use of paracetamol can increase blood pressure in people with hypertension who are already at increased risk of heart attacks and strokes. It emphasises why doctors and patients should regularly review whether there is an ongoing need to take any medication, even something that may seem relatively harmless like paracetamol, and always weigh up the benefits and risks. However, if you take paracetamol occasionally to manage an isolated headache or very short bouts of pain, these research findings should not cause unnecessary concern.”
A consensus statement by 13 doctors in different countries suggests that pregnant people only take paracetamol/acetaminophen if it is medically necessary, Their paper, published in the journal Nature Reviews Endocrinology, the group paracetamol/acetaminophen (APAP).
In the same journal issue, an accompanying Editorial outlines the consensus statement and noting that its authors are not calling for a ban on the drug being used, instead they are suggesting that it be taken more cautiously by pregnant women because of a possible risk of birth defects.
Research in recent years has shown that it is possible under some circumstances for APAP to alter foetal development which can herald problems with neurological, urological and reproductive disorders in the baby – the authors found evidence of birth defects in 26 out of 29 studies. The authors call for more research into the possible problems with the drug’s use by pregnant women. They also acknowledge – as do several experts in a reaction piece published on the Science Media Centre site– that APAP is the only pain management drug available for pregnant women. And they point out that medical use of APAP is generally warranted when the mother experiences problems that can negatively impact her baby – such as having a fever. But they also note that pregnant women’s APAP use appears to have crept up into general use as it has gained a reputation as being safe to use as an all-purpose painkiller.
The expert group and the authors of the new paper notably both point out that the recommendation does not differ from that already in use by most OB/GYNs – and similar wording generally appears on bottles of products based on APAP, such as Tylenol.
The consensus statement’s authors say their intention behind the article is to bring renewed and more focused attention to the possibility of APAP use leading to certain birth defects and the conditions under which they might arise. They note that current research has shown, for example, that the risk of harm seems to rise as the duration of APAP use goes up. In light of this, they suggest pregnant women consider using the drug for short term pain management, rather than as a long-term solution.