The period between winter and spring is known to be ‘bad’ when it comes to the possibility of catching a flu or cold: temperature changes, doubts about what to wear, unexpected rain—and there we are with tissues and over-the-counter remedies. One of the most common is paracetamol, a painkiller and antipyretic.
Safe, but not for the elderly and not for long-term use
Paracetamol has always been considered a safe medicine and is often recommended for the treatment of osteoarthritis—a chronic painful condition that is very common in people over the age of 65. But a study conducted by the University of Nottingham and based on data from more than 180,000 patients with an average age of 75 found a correlation between long-term use of paracetamol and an increased risk of serious complications.
According to this research, continuous use of the medicine for six months or more was associated with:
- 36% increased risk of gastrointestinal bleeding;
- 20% increased risk of peptic ulcers;
- 19% increased risk of chronic kidney disease;
- 9% increased risk of heart failure;
- 7% increased risk of high blood pressure.
The data also shows a clear dose-response relationship: the more the medicine is prescribed and taken, the greater the risk of developing potentially dangerous side effects.
These findings are not conclusive, says Silvio Festinese
It is important to stress that this is an observational study and it is not possible to establish with absolute certainty a direct cause-and-effect relationship between paracetamol use and the occurrence of these complications. However, the results do suggest the need for greater caution on the part of medical practitioners when prescribing long-term paracetamol, especially in elderly patients, as well as greater awareness on the part of people taking paracetamol.
To find out more, we interviewed Silvio Festinese, a specialist in Cardiology and lecturer in Pharmacology at UniCamillus University.
Do you think the Nottingham study used an appropriate methodology to reach its conclusions? Or do you think further research is needed?
“The design of this study is an observational cohort study using data from the Clinical Practice Research Datalink (CPRD). Let me explain what an observational cohort study is. It is a study where researchers follow a group of people (cohort) over a number of years. Cohorts are groups of people who are selected on the basis of certain common characteristics, divided into subgroups because of differences in their exposure to a particular agent (in this case a medicine), and followed up by a measurement system to see if they develop a particular disease or any complications. Prospective cohort studies identify cohorts at the start of the study and follow them over time. However, as this implies simply ‘observing’ people, conclusions are not definitive; rather, they represent a starting point for further and different findings“.
Were the reported long-term side effects already known? If so, what is new about them?
“The major side effects of chronic paracetamol use, such as hypertension, heart failure, kidney failure, and gastrointestinal bleeding, were already known. This observational study aimed to draw attention to the relationships between duration of use, dosage and major complications in elderly patients. This is a patient group that needs more attention in clinical practice and more studies in pharmacological research”.
Are there categories of patients who should use paracetamol cautiously or avoid it altogether?
“First and foremost, children and the elderly: for different reasons, both should use paracetamol with caution, avoiding self-administration of the medication and following their GP’s instructions carefully”.
Is there a safe maximum dose for elderly patients? And what is meant by ‘long-term use’?
“Medicines are metabolised and excreted by the liver and kidneys: elderly patients must always be treated according to their specific liver and kidney function. This means avoiding both exceeding the maximum dose and exposing the patient to serious side effects, and underdosing and exposing the patient to serious risks and complications from the disease being treated.
Routine blood tests (creatinine, uric acid, GFR, microalbuminuria, transaminases, GGT, bilirubin, complete blood count, etc.), analysed in the light of the patient’s age, sex, weight, height, BMI, abdominal circumference, provide this information for increasingly personalised care of the elderly patient, who is often also frail, with the aim of reducing the risk of complications”.
Some elderly people use paracetamol for chronic pain: are there any safer and equally effective alternatives?
“Several international guidelines on pain treatment (e.g. for orthopaedic, neuropathic, oncological pain) agree on the use of paracetamol in the first instance, up to higher doses. Gradually, other molecules can be combined, such as peripheral and central nervous system painkillers. It is always important to put the patient’s condition in context with a precise calculation of the cost-benefit ratio, and then to agree on the choice. Therapeutic alternatives do exist, but it is difficult to establish and measure the effectiveness and safety of the various treatments being compared: there are not enough scientific studies”.
Do you think more control over the sale of paracetamol would be useful?
“The availability of over-the-counter substances/drugs without a prescription is an unresolved issue because it raises clinical questions of considerable importance, such as pharmacological interactions, overdoses, acquired hypersensitivities, delays in diagnosis. There are some disorders that can be caused by the misuse of OTC medicines, such as electrolyte disturbances, hypervitaminosis, secondary hormonal changes, secondary hypertension”.
What advice would you give to people who take high doses of paracetamol?
“I believe that the use of high doses of paracetamol is always a consequence of a well-defined clinical picture: only close collaboration with your GP will avoid and reduce the risks of paracetamol’s side effects in the chronic elderly patient, who is also often frail. As the chronic disease progresses, the best dosage, the best combination with other molecules or the possible substitution with other principles can be determined. Personalising therapies as much as possible through ‘precision medicine’ will be one of the next exciting challenges“.