Pain Medicine News
POSTED: JANUARY 21, 2014
Following the FDA’s announcement that it is asking physicians and other health care professionals to stop prescribing combination drugs that include more than 325 mg of the analgesic and fever reducer acetaminophen, medical professionals, journalists, pain patients and members of the general population alike took to the Web and to social media to weigh in on the ruling.
“Acetaminophen doses over 325 mg might lead to liver damage?,” wrote one individual on a social media site. “It’s been on the market for 50 YEARS and it took TIL NOW to tell us it DAMAGES the LIVER?”
Actually, it was 60 years ago when McNeil first marketed paracetemol (the better known generic name of acetaminophen at the time) in combination with sodium butabarbital, under the trade name Algoson. And of course, liver toxicity from high doses of acetaminophen has been chronicled in the medical literature for years. Overuse of acetaminophen is far and away the most common cause of acute liver damage in the United States It is believed that taking higher-than-recommended doses of acetaminophen is quite common, with one study reporting that almost 40% of patients with acute liver failure related to unintentional acetaminophen overuse were taking two or more preparations of the painkiller simultaneously (Clin Gastroenterol Hepatol 2008;6:918-925; quiz 837).
(The FDA, in a January 14 press statement, acknowledged that multiple acetaminophen sources taken simultaneously have led to the majority of the toxicity cases. It also warned against taking more than the recommended dose over a 24-hour period and drinking alcohol in combination with acetaminophen.)
And although the data proving the magnitude of the problem is indeed there, so is the paper trail left by the FDA as it attempts to address the growing issue. For pain physicians and other health care professionals, the FDA’s actions are most likely seen as the next step in the ongoing effort to reduce the risk for potentially fatal liver damage with acetaminophen use.
A Record of Action
The FDA said in the press statement that there is no data showing that doses greater than 325 mg “provide additional benefit that outweighs the added risks for liver injury.” Many of the moves the agency has made over the past five years with regard to acetaminophen have been made with the dangers of high doses of the drug in mind.
In 2009, the FDA required manufacturers of over-the-counter (OTC) painkillers and fever reducers to post a warning on their labels of the potential for stomach bleeding and liver damage.
That same year, an FDA advisory committee recommended strengthening the warning about severe liver injury on the drug labels of prescription products containing acetaminophen. The 2009 panel also voted in favor of lowering the maximum daily dose of acetaminophen to less than the current 4,000 mg; reducing the maximum single adult dose from 1,000 to 650 mg; making the 500-mg pill obtainable by prescription only; and—in perhaps its most controversial recommendation—eliminating all prescription products that combine acetaminophen with certain other drugs, like narcotics, from the market.
In January 2011, the FDA followed two of the panel’s recommendation. It issued a black box warning regarding liver toxicity for prescription combination products that contained acetaminophen. It also moved to limit the amount of acetaminophen in each pill to 325 mg, setting Jan. 14, 2014 as the deadline by which to comply. In a press statement this week, the FDA said that roughly half of manufacturers have voluntarily complied with the requirement, adding that, “In the future, FDA intends to institute proceedings to withdraw approval of prescription combination drug products containing more than 325 mg of acetaminophen per dosage unit that remain on the market.”
In October 2013, the FDA issued warnings on potential serious, life-threatening rashes associated with acetaminophen use, including Stevens-Johnson syndrome and toxic epidermal necrolysis. The FDA required prescription drugs containing acetaminophen to include a warning about potential skin reactions, and announced it would to so with OTC agents in the future.
Exceptions Can Be Made, More Action to Come
The FDA’s warning came with that caveat that in some cases physicians could prescribe up to two tablets containing a maximum of 650 mg of acetaminophen, if appropriate, but stressed the need to consider both the amount of acetaminophen and the prescription painkiller (e.g., opioid) in the tablet being prescribed. The agency also stressed that pharmacists who receive a prescription totaling more than 350 mg acetaminophen should contact the physician and discuss lower dose alternatives.
The FDA promised that it will continue to work toward fixing the problem, writing in the press statement, that it will “address OTC acetaminophen products in another regulatory action.”
More information and a list of the products affected by the new ruling can be found at www.fda.gov/acetaminophen—Donald M. Pizzi