UC Davis study reveals potential for toxic doses of acetaminophen

“Although small, the number of patients who could have taken 16 grams or more for at least one day is very concerning,” said lead author Timothy Albertson, acting chair of internal medicine for UC Davis Health System, “and the fact that many patients had total prescriptions that could have resulted in more than 100 days of four grams per day or more is truly alarming.”

Commonly sold over the counter under the brand name Tylenol, acetaminophen is one of the most popular pain-relief medications worldwide. It is frequently included in over-the-counter cold treatments and with prescription medications, making it easy for consumers to reach the four-grams-a-day or higher mark. Multiple case reports have suggested that four to six grams per day — especially if taken over time or in combination with alcohol — may induce liver or kidney damage in healthy and vulnerable patients alike.

“We have to be concerned about prescriptions for pain relief because nearly all of them contain acetaminophen, and it’s possible that significant amounts will be consumed daily or over the course of a few days,” said Albertson. “Better systems and stronger education of patients, prescribers and pharmacists are needed to reduce potential toxic exposure.”

Albertson and his team examined pharmacy claims within California’s Medicaid (known as MediCal) program for medications, including over-the-counter medications, that could result in acetaminophen doses exceeding four grams per day. They found that during 12 months in 2004 and 2005, an average of about 3.27 million beneficiaries were enrolled in the MediCal program and 961,320 of them, or 29.4 percent, received one or more prescriptions that included acetaminophen. If taken as directed, a total of 192,716, or 5.9 percent, were exposed to at least one day of acetaminophen doses exceeding four grams per day. Of those, 769 patients were potentially exposed to at least one day of 16 grams per day or more, and 2,664 beneficiaries were exposed to 100 days or more of acetaminophen doses of four grams per day or more.

Sixty-one patients with claims for four grams per day or greater of acetaminophen for more than 100 days had a diagnosis of primary liver or renal dysfunction, which the study team also found to be alarming.

Albertson pointed out that a recent Food and Drug Administration advisory committee recommended reducing the maximum total daily dose of acetaminophen and increasing outreach to health-care providers and consumers about the risks of overdose. To reduce the potential for over-prescribing the medication, he and his research team also recommend:

  • Using electronic health-records systems to notify and potentially block excessive acetaminophen dosing.
  • Increasing regulation of products containing acetaminophen.
  • Conducting additional research to investigate the link between chronic high-dose acetaminophen exposure and an increased risk of acute or chronic liver or kidney disease.

“Acetaminophen has provided a good pain-relief alternative, especially for those who are unable to take medications like aspirin due to stomach irritation,” said Albertson. “But that doesn’t mean that it is safe in all instances or in all amounts. We need to be just as careful with this medication as we are with others.”

Additional study authors included Victor M. Walker Jr. of the California Department of Health Care Services; Marilyn R. Stebbins and Elisa W. Ashton of UC San Francisco and Catholic Health Care West; Kelly P. Owen of the UC Davis School of Medicine and Veterans Affairs Northern California Health Care System; and Mark E. Sutter of the UC Davis School of Medicine. 

A copy of “A Population Study of the Frequency of High-dose Acetaminophen Prescribing and Dispensing” can be downloaded at www.theannals.com.

The UC Davis School of Medicine is among the nation’s leading medical schools, recognized for its research and primary-care programs. The school offers fully accredited master’s degree programs in public health and in informatics, and its combined M.D.-Ph.D. program is training the next generation of physician-scientists to conduct high-impact research and translate discoveries into better clinical care. Along with being a recognized leader in medical research, the school is committed to serving underserved communities and advancing rural health. For further information, visit the UC Davis School of Medicine website.