High Dose Pain Reliever Paracetamol -Acetaminophen Linked to Increase in Overdoses

PainRelief.com Interview with:
Andrea Burden, Ph.D.
Assistant Professor of Pharmacoepidemiology
Institute of Pharmaceutical Sciences
Zurich Switzerland

PainRelief.com:  What is the background for this study?

Response: Paracetamol (also known as acetaminophen) is one of the most commonly used medications in the world. While the drug is generally safe, daily intake exceeding 4,000 milligrams (4 grams) can lead to irreversible liver injury and even death. Traditionally in Europe, paracetamol is available in two dose formulations, the 500 and 1,000 milligram tablets. The lower dose formulation is often available over-the-counter (without a prescription), while the high-dose formulation requires a medical prescription. In the last decade, there has been accumulating evidence that both the availability of high-doses of paracetamol, and the quantity of paracetamol available to patients, are associated with the risk of overdose. Therefore, in this study, we aimed to identify if there was an increase in the number of calls to the National Poison Information Centre in Switzerland for paracetamol-related overdoses after the high-dose 1,000 milligram (1 gram) paracetamol tablets became available in October of 2003. We also examined if there were differences in the circumstances of the overdose and severity between the 500 milligram or 1,000 milligram tablets.

PainRelief.com: What are the main findings?

Response: We identified that sales of the high-dose 1,000 milligram paracetamol tablets increased rapidly following the introduction in October 2003 and surpassed the sales of the 500 milligram tablets within 2-years. Using an interrupted time series analysis of the National Poison Centre data, we could identify that the number of paracetamol-related overdoses significantly increased following October 2003. Importantly, we found that the significant increase was only among accidental circumstances, meaning the patient did not intentionally exceed the daily limit. When we looked at the differences between the formulations, we found more accidental and more severe (cases with ingested doses above 10,000 milligrams) overdoses with the 1,000 milligram tablets than with the 500 milligram tablets.

PainRelief.com: What should readers take away from your report?

Response: Our study results suggest that access to high-dose paracetamol can increase the risk of an accidental overdose. This is important because these cases are preventable. Paracetamol is frequently used to treat short-term pain, such as fever, small injuries, or post-surgical pain. However, despite lacking evidence of effectiveness, many patients are prescribed paracetamol to manage long-term chronic pain. This is where the problem of the 1,000 milligram tablets can emerge. If patients do not receive adequate pain relief, they may increase the frequency or quantity of paracetamol without thinking about the dangers. With the 1,000 milligram tablets, exceeding the 4,000 milligram daily threshold is easier than with the 500 milligram tablets.  For instance, a patient need only take four tablets to reach the threshold with the 1,000 milligrams compared to eight 500 milligram tablets.

Improved awareness of the problem can mitigate many of these mistakes. Doctors and pharmacists should explain the proper use of paracetamol to their patients, emphasizing the dangers of exceeding the maximum daily consumption limit (e.g., four tablets per day if prescribing the 1,000 milligram formulation) and reminding patients that it should not be used for long-term (chronic) pain management. Patients should also be told to consult their doctor before considering increasing the frequency of paracetamol consumption if they do not experience pain relief with the recommended dose.

PainRelief.com: What recommendations do you have for future research as a result of this work?

Response: Future research should examine the safety of chronic exposure to high doses of paracetamol. It is unclear how many patients use paracetamol for chronic pain management, consuming 2,000 – 4,000 milligrams daily, and if this long-term exposure may have negative consequences on the liver.

PainRelief.com: Is there anything else you would like to add?

Response: Our results support previous research showing that accidental overdoses of paracetamol are increasing in many nations. This has led to many countries reducing the availability of the pack-sizes available to patients without a prescription (over-the-counter) and requiring a prescription for larger quantities and higher doses. However, our study indicates that, even when prescribed, the availability of a high-dose formulation of paracetamol can increase the number of accidental overdoses. Thus, limitations on over-the-counter sales or requiring a prescription for the high-dose will not fix the problem. Instead, public health measures to raise awareness of the dangers of exceeding the daily limit of paracetamol and restrictions on the use of the high-dose formulation are needed.

No disclosures.


Martinez-De la Torre A, Weiler S, Bräm DS, Allemann SS, Kupferschmidt H, Burden AM. National Poison Center Calls Before vs After Availability of High-Dose Acetaminophen (Paracetamol) Tablets in Switzerland. JAMA Netw Open. 2020;3(10):e2022897. doi:10.1001/jamanetworkopen.2020.22897

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Last Updated on November 3, 2020 by PainRelief.com