The addition of liver toxicity and overdose risk warnings to acetaminophen labels may not be enough to reduce the high prevalence of overdosing of the painkiller, say researchers in a recent study.

The authors state in the May 26 Journal of General Internal Medicine that interviews with 500 adults between September 2009 and March 2011 reveal many consumers have extensive prior experience with OTC painkillers and no longer closely read labels. They often do not adhere to package or label instructions, and as a result likely would be unaware of or ignore label changes that industry voluntarily made and FDA ordered intending to reduce the risk of liver toxicity due to unintentional overdose.

The label changes, which occurred while the study was in process, include placing the active ingredient prominently on the product’s principal display panel and adding new warnings about the risk of liver toxicity due to overdose or simultaneous use with alcohol Also see "FDA Expands Acetaminophen, NSAID Labeling Beyond Tentative Final Rule" - Pink Sheet, 4 May, 2009..

In addition, labeling for McNeil Consumer Healthcare’s Extra Strength Tylenol now indicates a maximum dose of six pills – or 3 grams – daily versus the eight pills previously recommended, the researchers note Also see "McNeil Lowers Recommended Maximum Dose For Extra Strength Tylenol" - Pink Sheet, 1 August, 2011.. Industry also investigated adding an acetaminophen icon to the OTC drug facts label that could reduce concomitant use of multiple acetaminophen-containing products ([A#110531t1]).

Researchers led by Michael Wolf of the Health Literacy and Learning Program at the Feinberg School of Medicine at Northwestern University lauded the changes as “appropriately targeted [to] the OTC product with the greatest risk for consumer overdose,” and recognized that “increasing awareness of the dangers of liver toxicity with acetaminophen use is clearly a public health goal.” But, they explained, the label changes are only effective if consumers read and understand them, which their research indicates is not happening with acetaminophen OTCs.

Through their interviews, Wolf and colleagues found 23.4% of participants would overdose on a single OTC acetaminophen product by exceeding the 4 grams per 24-hour dose, and that 5.2% would make “serious errors” and overdose by more than 6 grams a day. Because a dangerous overdose of acetaminophen is only slightly more than a dose needed for efficacy, even slightly exceeding the recommended dose is dangerous.

Participants were more likely to exceed the maximum daily dose of 4 grams with the 1,000 mg/dose products (17.5%) and least likely to with the 500 mg/dose medicines (6%), the researchers add.

In addition, they found many consumers apparently do not recognize or differentiate the active ingredient in OTC pain medicines and are at risk of overdose by “double-dipping.” Nearly half of the participants interviewed demonstrated that they would overdose by taking more than one product with acetaminophen at the same time, according to the study.

Specifically, in addition to a single-ingredient acetaminophen pain reliever, 21.7% said they could take a cold and cough medicine with acetaminophen, 21.1% said they could take a sinus medication with acetaminophen and 21.3% said they could take a nighttime pain reliever.

The researchers hypothesize that this occurs because consumers are not often exposed to what the active ingredient of an OTC product means and its importance in the safety and efficacy of a medication. They say consumers likely base their dosing decisions not on the ingredient, but on the indications advertised on the front of packages and in marketing.

“It could be that symptom relief advertised on the product suggests to consumers that the products contain different medicines, and that dual use might be safe,” they say.

Double-dipping also could be attributable to the number of products that include acetaminophen. Nearly 600 products contain the ingredient, according to the Consumer Healthcare Products Association, which is working to reduce the risk of acetaminophen overdose.

CHPA takes these studies seriously and benefits from the consumer behavior insights, but considers the findings within the context of more than 50 million U.S. consumers using acetaminophen safely each week, a spokeswoman said.

She also noted this study tests hypothetical consumer behavior that does not reflect real-world results. The risk and occurrence of overdose actually is much lower, or the rates of liver damage would be much higher than what is currently reported, she added.

The authors also recognize that their results reflect hypothetical behaviors, but say it is equally reasonable to suggest the estimates of overdose are conservative. Therefore, they suggest the Federal Trade Commission require display of active ingredients in OTCs on the front of packages and in ads, in addition to the existing practice of highlighting the ingredient in the Drug Facts box.

The researchers also recognized other “ongoing opportunities” to impact label standards, educate consumers and reduce unintentional misuse of OTCs containing acetaminophen, such as the Safe Use Initiative, the “Know Your Dose” campaign launched by CHPA, FDA and others, and the PROTECT initiative (Also see "Acetaminophen Awareness Coalition Prepares To Launch Education Campaign" - Pink Sheet, 22 November, 2010., Also see "FDA Launches Safe Use Initiative; Details TBA Following Stakeholder Input" - Pink Sheet, 9 November, 2009. and Also see "Campaign Targets Unsupervised Pediatric Drug Ingestion" - Pink Sheet, 19 December, 2011.).

The challenge is “to adequately educate the public that there are potential safety hazards of using OTC products, and it is important to always 1) know the active ingredient of an OTC medicine, 2) closely read and follow directions, 3) attend to any label warnings or precautions,” the researchers conclude.

The researchers conducted the study in response to an FDA advisory panel meeting called in 2009 to assess the risk of liver toxicity due to acetaminophen and to brainstorm ways to reduce the risk. The panel found the majority of overdoses appear unintentional and determined that OTC drug labeling is a likely root cause, but noted the limited availability of evidence Also see "Lower Acetaminophen Doses Recommended Despite Cost Impact, Lack Of Data" - Pink Sheet, 6 July, 2009..

Acetaminophen Overdose Risk Persists Despite Label Changes – Study

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