A Healthesystems publication

Spring 2014

FDA Actions Address Acetaminophen Toxicity Risks

The FDA recognized the risks of high doses of acetaminophen by asking prescription drug manufacturers to lower the maximum content per pill or capsule by January 2014. The request did not apply to over-the-counter preparations, so risks will remain until all the supplies of all high-content formulations are depleted.

In high doses, acetaminophen can cause toxicity and lead to serious liver damage or even death. In 2011, the National Council for Prescription Drug Programs (NCPDP), FDA and other interested parties focused attention on patient safety issues with the formation of the Acetaminophen Best Practices Task Group.1

To minimize patient risks, the FDA asked prescription drug manufacturers to limit acetaminophen content to a maximum of 325mg per tablet or capsule by January 1, 2014.2 The high dose acetaminophen products seen most frequently in workers’ compensation are Vicodin®HP, Vicodin® ES, Percocet® products, Lortab® and their generic versions.

In response to the FDA request, many manufacturers reformulated their products and received FDA approval for reduced acetaminophen content. Brand names were retained and a few products were discontinued. Generic manufacturers also complied with the request. As a result, there should be no impact on the use of generic products as substitutes for brand-name prescriptions with the lower acetaminophen dose.

The FDA made a provision for manufacturers and retailers to deplete existing supplies. Since they were permitted to continue manufacturing the higher dose products until the 2014 deadline, higher dose products remain on the market. Until supplies of the higher strength products are depleted, patients remain at higher risk for excessive use. This is especially true for patients who may take over-the-counter (OTC) formulations and prescription preparations containing acetaminophen since the FDA request did not apply to OTC.

Enhanced Patient Safety

The FDA is urging prescribers to use the lower dose formulations even if the older formulations are still available.3 Encouraging prescribers to reduce acetaminophen use and educate patients remains important in curbing patient risks. The limits placed on one source of acetaminophen and the increased awareness of patients, prescribers and insurers of the risks of taking too much should improve patient safety.

Healthesystems saw a 63% decrease in acetaminophen prescriptions containing > 2600 mg daily between 2012 and 2013. It is possible that all the attention being focused on the risks, combined with strategic intervention, is having a positive effect.

Safe Medication Use

Patient education is one of the key factors that influence safe medication use. All parties involved in patient care need to help patients understand which products contain acetaminophen and the daily use limits. Patients should be expected to keep track of all medical products they are using, both prescription and OTC, and total up daily acetaminophen milligrams to avoid overuse. The FDA website has a wealth of information for patients.4

Avoiding Acetaminophen Toxicity

Regardless of the actions taken to protect patients, acetaminophen use remains a concern. Thousands of prescription and over-the-counter products contain this useful drug. All healthcare providers need to be alert to the presence of this common drug and help patients limit use to safe doses.

FDA Labeling Changes For OTC Products

Over-the-counter (OTC) products were not included in the FDA’s reformulation request though labeling changes were requested.5 Many consumers are not aware of the amount of acetaminophen contained in products. Even worse, consumers may not have realized acetaminophen was even present. Acetaminophen is a common ingredient in sleep aids and products made to treat general pain, coughs and colds, headaches and menstrual cramps.

Labeling changes requested to improve over-the-counter product identification included:6

Look For Acetaminophen on the Label

Here is an example of how easy it is to exceed the recommended daily dose of acetaminophen. This patient is taking a prescription analgesic, cold medication and sleep aid. All contain acetaminophen.


Top 5 Acetaminophen Preparations in Workers’ Compensation*

Product Acetaminophen Content Before Change Acetaminophen Content After Change Generics Available?
Vicodin HP 660mg 300mg Yes
Vicodin ES 750mg 300mg Yes
Percocet family of products 325mg up to 650mg All now 325mg Yes
Lortab 500mg Product discontinued N/A
Lorcet, Lorcet Plus 650mg Product discontinued N/A

*Based on a Healthesystems clinical analysis.

Many Factors Influence Acetaminophen Risks

A number of factors can escalate a patient’ risks for acetaminophen toxicity. They include excessive daily doses, concurrent alcohol consumption, diminished liver function, concurrent use of over-the-counter medications containing acetaminophen, kidney disease and smoking.

Healthesystems’ ongoing clinical outreach program alerts payers and prescribers to these risks and provides an opportunity for intervention to reduce the risks. This program was in place even before the FDA made its request to pharmaceutical manufacturers for a reduction in per pill and per capsule content. Excessive acetaminophen use is too important an issue to ignore. The risks are of liver damage and liver failure are serious and potentially fatal. The loss of even one life and the need for a single liver transplant are too high a price to pay.

Acetaminophen Newsworthy Highlights



1 -U.S. Food and Drug Administration. Rockville, MD. Acetaminophen Information. http://www.fda.gov/drugs/drugsafety/informationbydrugclass/ucm165107.htm. February 22, 2014.
2 -U.S. Food and Drug Administration. Rockville, MD: FDA Drug Safety Communication: Prescription Acetaminophen Products to be Limited to 325 mg Per Dosage Unit; Boxed Warning Will Highlight Potential for Severe Liver Failure. http://www.fda.gov/drugs/drugsafety/ucm239821.htm. February 22, 2014.
3 -U.S. Food and Drug Administration. Rockville, MD. FDA recommends health care professionals discontinue prescribing and dispensing prescription combination drug products with more than 325 mg of acetaminophen to protect consumers. http://www.fda.gov/Drugs/DrugSafety/ucm381644.htm. February 22, 2014.
4 -U.S. Food and Drug Administration. U.S. Food and Drug Administration. Rockville, MD. Acetaminophen Information. http://google2.fda.gov/search?q=acetaminophen&client=FDAgov&site=FDAgov&lr=&proxystylesheet=FDAgov&requiredfields=-archive%3AYes&output=xml_no_dtd&getfields=*. February 22, 2014.
5 -U.S. Food and Drug Administration. Rockville, MD. Questions and Answers on Final Rule for Labeling Changes to Over-the-Counter Pain Relievers. http://www.fda.gov/drugs/newsevents/ucm144068.htm.
6 -U.S. Food and Drug Administration. Rockville, MD. Questions and Answers on Final Rule for Labeling Changes to Over-the-Counter Pain Relievers. http://www.fda.gov/drugs/newsevents/ucm144068.htm. February 22, 2014.
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