The initial questions a health care professional asks when a patient presents with an acetaminophen overdose are, “When did you take acetaminophen, and how much did you take?” Subsequent questions assess if the patient has any risk factors that may enhance toxicity. Underlying hepatorenal disease, especially hepatitis; fasting or malnutrition; alcohol use; and concomitant medicine use may increase the risk for life-threatening acetaminophen toxicity.
If the bottle the pills came from is not available for inspection, there is one important question that may get overlooked, with potential serious consequences for the patient’s recovery: “What kind of acetaminophen did you take (ie, was it immediate- or extended-release)?” This question is important because the difference in pharmacokinetics between immediate-release (IR) and extended-release (ER) acetaminophen may result in the need for additional acetaminophen concentration monitoring and a longer regimen of the antidote N-acetyl cysteine (NAC), which is used for mitigation of acetaminophen overdose–induced liver injury. Reports in the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) indicate it is difficult to distinguish between the use of IR and ER acetaminophen in cases reporting accidental and intentional overdose.
There is much ongoing research on this topic. In December 2017, the European Medicines Agency endorsed a recommendation to suspend marketing of paracetamol modified-release products (also known as acetaminophen ER) since, in the European Union, the advantages of a longer-acting product did not outweigh the complications of managing an overdose. Unlike with the IR formulation, a standardized way to manage acetaminophen ER overdose using NAC has not been established. These developments make safety issues related to acetaminophen ER a concern for the FDA.