What exactly is a "black box" warning?
Simply put, it's the strongest warning that the U.S. Food and Drug Administration (FDA) can require on a drug's packaging. The FDA requires the black box warning when studies suggest a drug can cause a serious or life-threatening side effect. The text of the warning is set apart from other information in a black box, so that doctors, pharmacists, and patients can easily see it.
What did the FDA advisory panel recommend?
The FDA itself hasn't made a decision about acetaminophen, but an FDA advisory panel has made 10 recommendations concerning the drug. Among those recommendations, the panel voted to remove acetaminophen-containing painkillers such as Vicodin, Tylenol 3, and Percocet from the nation's formularies. It also voted in favor of removing all acetaminophen-containing prescription drugs from the market.
But the panel voted to keep over-the-counter (OTC) pills that combine acetaminophen and other ingredients, such as caffeine.
The panel also recommended that the FDA lower the daily total dose to less than 4,000 mg, and the total adult dose from 1,000 mg to 650 mg.
What happens now?
The FDA is not required to follow the recommendations of an FDA advisory panel, but they often do. Nothing will be changed until the FDA makes its final decision on acetaminophen.
How does acetaminophen damage the liver?
As with so many medications, acetaminophen is processed by the body in the liver. There, the drug undergoes two processes, one called sulphation and one called glucuronidation. These take place along two pathways, one for each process, and once they are finished, the actual acetaminophen and the sulphation and glucuronidation compounds that the liver has made from the drug are eliminated from the body.
This whole process typically happens without harming the liver. But if there is too much acetaminophen, the two pathways that help break down the drug become flooded and stop working. This forces the drug down another “breakdown” pathway in the liver called the cytochrome P-450 system. This is where the problem starts for the liver, because when acetaminophen goes down this pathway, it produces a toxic compound called NAPQI. This poisonous substance builds up in the liver and causes serious damage.
Even worse, if a person is taking other medications, including phenobarbital, an anti-seizure medicine such as Tegretol, or certain tuberculosis drugs, this damage is even greater because these drugs “switch on” the cytochrome P-450 system and make it even more active. And if a person drinks alcohol excessively, the liver produces more NAPQI. Add too much acetaminophen, and the damage is even worse.
