In an attempt to err on the side of safety, an advisory panel to the Federal Food and Drug Administration narrowly voted yesterday to ban the popular prescription pain medications Percocet and Vicodin, in a 20-17 vote.[1 ]Both medications are a combination of a narcotic and acetaminophen, and according to the New York Times, it was a growing concern over the safety of acetaminophen that prompted the Drug Safety and Risk Management Advisory Committee to assemble in Adelphi, Maryland early this week.
Acetaminophen is one of the most popular pain medications in the world , and though highly effective in reducing fevers and treating headaches, there has always been great concern for hepatotoxicity. In fact, between 1998 and 2003, the most common cause of acute liver injury was this medication. In the United States alone, it is estimated that nearly 400 people die and 42,000 patients are hospitalized resulting from overdose. Almost half of these cases are unintentional.
When ingested in large quantities, acetaminophen has the ability to cause severe centrilobular hepatic necrosis. Most of the medication is metabolized by a phase II reaction, but a small percentage is converted to NAPQI, a hepatotoxic metabolite via the cytochrome P450 pathway. Gluatathione is responsible for the detoxification by binding to NAPQI and forming the harmless, water-soluble mercaptopuric acid. However, when gluatathione levels are low, or when the CYP450 pathway is induced via alcohol, or Phenobarbital, or INH, the levels of NAPQI can quickly lead to acute liver injury.
The panel’s recommendations were not limited to only banning the combination medications, however. It also proposes that the FDA reduce the highest allowed dose in over-the-counter pills from 500 milligrams to 325 milligrams, and to reduce to maximum daily dosage to less than 4000 milligrams. Interestingly, the panel voted against reducing the maximum number of pills allowed in each bottle- citing concern that imposing such a limit would ultimately hurt rural and poor consumers.
Tylenol’s maker, Johnson and Johnson, “strongly disagrees” with the panel, and believes that limiting access to one pain medication will “lead to more serious adverse events as consumers shift to other over-the-counter products”.
Starting in the 1990’s, the FDA has sought to reduce the incidence of liver injury resulting from acetaminophen and continues to expand public knowledge about acetaminophen overdose. And though there is no obligation on the part of the federal agency to agree with and accept the panel’s recommendations, it typically does.
Dr. Turakhia is a 1st year resident in internal medicine at NYU Medical Center.
1. Harris, Gardiner. “Ban Is Advised on 2 Top Pills for Pain Relief.” New York Times. 30 June 2009. Newspaper on-line. Available from http://www.nytimes.com/2009/07/01/health/01fda.html?_r=2&hp. Accessed 1 July 2009.
2. USA Food and Drug Administration. “Joint Meeting of the Drug Safety and Risk Management Advisory Committee with the Anesthetic and Life Support Drugs Advisory Committee and the Nonprescription Drugs Advisory Committee Meeting Announcement.” http://www.fda.gov/AdvisoryCommittees/Calendar/ucm143083.htm. Accessed 1 July 2009.
3. Larson, A.M., J. Polson, R.J. Fontana, et al., Acute Liver Failure Study Group (ALFSG), ‘‘Acetaminophen-Induced Acute Liver Failure: Results of a United States Multicenter, Prospective Study,” Hepatology 2005, Dec;42(6):1364-72.
4. Dienstag Jules L, “Chapter 299. Toxic and Drug-Induced Hepatitis” (Chapter). Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo J: Harrison’s Principles of Internal Medicine, 17th Edition: http://www.accessmedicine.com/content.aspx?aID=2873966.