Acetaminophen overdoses and Physician/Pharmacist Errors
Physicians may not take into consideration the amount of acetaminophen prescribed when they write prescriptions that combine acetaminophen with narcotics such as oxycodone. Such prescriptions may be safe in terms of the amount of oxycodone but are unsafe if the dosage exceeds the maximum daily limit of 4 grams of acetaminophen. Pharmacists who fill such prescriptions are duty bound to not fill such prescriptions. In such instances, both the physician and pharmacist are legally liable for prescriptions that lead to an overdosage of acetaminophen.
If you use Tylenol, its generic counterpart acetaminophen, or combination medications that contain acetaminophen, you may be at risk for liver damage. With almost 25 billion doses sold in 2008, acetaminophen is one of the most commonly used drugs in the United States. When taken at usual therapeutic doses, acetaminophen is remarkably safe compared to other analgesics.
Yet, acetaminophen overdosage is public enemy number one for calls to Poison Control Centers. Each year from 1990 to 2001, acetaminophen accounted for approximately 56,000 emergency room visits, 26,000 hospitalizations, and 450 deaths in the United States. In fact, in the United States, unintentional acetaminophen overdosage is the most common cause of acute liver failure and acetaminophen accounts for more overdoses and overdose deaths than any other pharmaceutical agent. Given that drug manufacturers rarely disseminate or highlight safety information pro-actively, patients must rely on health care professionals and their own resources.
While there is scientific agreement that taking a large amount of acetaminophen over a short period of time causes liver injury, the medical community has not stepped up educational efforts and surveillance in response to the widespread danger. Physicians, physician assistants, nurse practitioners, nurses, and pharmacists must instruct about and carefully monitor their patients’ total acetaminophen ingestion – both prescription and over-the-counter (OTC). Health care professionals should inquire about acetaminophen ingestion every visit and pharmacists should review patient’s drugs every time a drug, especially one containing acetaminophen, is dispensed.
On June 29 and 30, 2009, FDA convened a Joint Panel of the Drug Safety and Risk Management Advisory Committee, Nonprescription Drugs Advisory Committee, and the Anesthetic and Life Support Drugs Advisory Committee to discuss the acetaminophen hepatotoxicity epidemic.
Panel members considered the factors underlined below, all of which make it difficult for the patient alone to protect his or her health:
The therapeutic margin is small such that recommended doses and tablet strengths leave little room for error. Taking a small amount over the recommended total daily dose (4 grams) may lead to liver injury.
Some individuals may be especially sensitive to liver injury from acetaminophen.
There are thousands of prescription and over-the-counter acetaminophen medications in different doses indicated for different uses. Some people simultaneously use the medications for different reasons, not realizing that acetaminophen is a common ingredient and that their total dosage is excessive.
It may be difficult to identify acetaminophen as a medication’s ingredient. Labels may refer to acetaminophen as APAP derived from the chemical name for the compound, N-acetyl-para-aminophenol. (Acetaminophen is called paracetamol outside North America.) A current television ad for Excedrin states that Excedrin is better than Tylenol for headaches leading consumers to conclude that it is a wholly different drug. Extra Strength Excedrin contains 250 mg. of acetaminophen, 250 mg. of aspirin, and 65 mg. caffeine.
Acetaminophen packaging in the United States reinforces the perception of safety. The medication is available in retail outlets and on the internet in large quantities, e.g. HealthWarehouse.com offers 1000 tablets or caplets per bottle, each 500 mg. (The 500-milligram tablets account for more than 90 percent of U.S. sales of single-ingredient acetaminophen.) By contrast, there is widespread use of blister packs in the UK where the maximum pack size was limited to 16 gm. in 1998 leading to a 30% reduction in the number of severe acetaminophen-induced acute liver failures in the following four years. France’s maximum pack size is 8 gm.
Liquid pediatric formulations are confusing in that those intended for use in infants are typically more concentrated to deliver proper dosing in less liquid. Giving the same concentrated drops to a young child can result in an accidental overdose.
The association between acetaminophen and liver injury is not common knowledge. Ever since McNeil Laboratories introduced acetaminophen as Tylenol Elixir for children in 1955, the drug has projected a very strong safety image. Johnson & Johnson acquired McNeil in 1959 and fortified that reputation with its “go the extra mile” response to the 1982 cyanide contamination incidents, temporarily disappearing the product from the market and introducing tamper-proof capsules and tamper-evident packaging, now the industry standard. Tylenol differentiates itself from other common analgesics such as aspirin known for gastrointestinal side effects and NSAIDs that pose increased cardiovascular risks. Over-the-counter drugs are not subject to the same offset requirements as prescription medications allowing makers to emphasize effectiveness and downplay warnings.
Though the patent has long expired, Tylenol enjoys continued success largely due to intense marketing, the backing of Johnson & Johnson, and new patented delivery schemes such as quick-release and extended-release. When the FDA Panel recently voted to lower the maximum daily dosage and transfer the 500 mg. dose to prescription status, J & J ran full-page ads in USA Today, the New York Times, The Wall Street Journal, and other newspapers, defending Tylenol as “the safest brand of pain reliever you can choose” when taken in the proper dosage. In 2008, Johnson & Johnson realized $5.9 billion in sales of over-the-counter drugs, including Tylenol, and nutritional products, while opening 176.9 million for Tylenol advertising. At the current rate of spending – not including the corporate response to the Panel’s findings — J & J will spend $217.2 million on Tylenol advertising alone.
How did the Joint Panel vote?
The Joint Panel voted as follows:
26 to 11 to render the 500-mg. dose available only by prescription
24 to 13 to lower the single adult dose to 650 mg. or two regular strength tablets, a reduction of 35 percent
21 to 16 that people should take less than 4000 mg of acetaminophen in a day
20 to 17 to ban Percocet and Vicodin which also contain a narcotic
The FDA is not bound by Panel recommendations. So, unless your health care provider is vigilant, BUYER BEWARE!