How much is too much? Acetaminophen overuse in the United States

Data from new study suggest reasons for misuse and potential solutions

A recent observational study detailing more than 4 years of acetaminophen use in the United States exposed the commonplace overuse of this widely accessible OTC analgesic, antipyretic, and antirheumatic drug. Data from this analysis suggested possible reasons for this misuse and possible potential solutions, and clarified which types of products were most likely to contribute to patients exceeding the recommended maximum daily dose.

The study assessed whether use of a particular single-ingredient formulation—325-mg immediate release (IR), 500-mg IR, or 650-mg extended release (ER)—was associated with a greater likelihood of exceeding the recommended 4-g daily limit for acetaminophen. With detailed daily diary data collected from online research panels for 7,579 adults, results showed that acetaminophen overuse was more likely to occur on days when patients used 650-mg ER products (8.9% of days vs. 4.4%; P < 0.0001; median on those days was 5.2 g).

Fortunately, acetaminophen overuse can be mitigated. “Approximately half of all acetaminophen-related hepatotoxicity is caused by unintentional overdose,” said Mark Holtsman, codirector of inpatient pain service and clinical professor of anesthesiology and pain medicine at the University of California Davis Medical Center. “We can decrease these overdoses by better monitoring and education.”

Acetaminophen is useful for managing chronic pain and mitigating fevers. It does not reduce inflammation, as do aspirin and NSAIDs like ibuprofen (i.e. Advil, Motrin) or naproxen (i.e. Aleve). Unlike NSAIDs, acetaminophen does not irritate the GI tract, so many people who cannot tolerate NSAIDs can still safely use acetaminophen.

One drawback to using acetaminophen is that taking too much can damage the liver, sometimes leading to hospitalizations, liver transplant, or death. The liver breaks down most of the drug into safe components that can be removed from the body in urine, but a small amount is metabolized to N-acetyl-p-benzoquinonimine (NAPQI). When taken in recommended doses, this toxic byproduct is quickly removed, but taking too much acetaminophen—either all at once or over a period of days—can build up more toxin than the body can handle.

In the average healthy adult, the general recommended maximum daily dose of acetaminophen is no more than 4,000 mg from all sources. In some people, however, doses close to this limit can still be hepatotoxic. Pharmacists should recommend that patients take only what they need and not exceed 3,000 mg per daily whenever possible, especially if using acetaminophen often.

“Patients with hepatic impairment or active liver disease,” said Holtsman, “should receive less than or equal to 2 grams of acetaminophen per day for the shortest time possible.” This would include those with alcohol-related cirrhosis and hepatitis B or C.

Trends detected in the study suggested possible reasons for acetaminophen overuse in the United States and implied potential solutions. Many patients, for example, were unfamiliar with the varying dosing intervals for different strength, single-ingredient acetaminophen products. This was especially true for the 650-mg ER 8-hour interval and often resulted in patients re-dosing too soon or using other acetaminophen-containing products within the same dosing interval.

Many consumers of typical OTC combination products, most often for upper-respiratory or allergy symptoms or sleeplessness, are unaware that they contain acetaminophen. For this reason, pharmacists should encourage patients to review the drug facts label for all their OTC medications and help monitor for acetaminophen contained in both nonprescription and prescription combination analgesic products.

For the full article, please visit for the November 2018 issue of Pharmacy Today.