Acetaminophen in Rx drugs: For liver’s sake, lower the dose, says FDA

<i>This post has been corrected. See the note below for details.</i>

Apparently, a Food and Drug Administration warning four months ago was missed by many physicians, pharmacists and patients, so the agency, in an unusual move, saw fit Monday to remind us: Stop writing prescriptions for, stop dispensing prescriptions for, and stop taking prescription medications containing more than 325 milligrams of acetaminophen.

Your liver will thank you -- acetaminophen overdose has overtaken viral hepatitis infection as the most common cause of acute liver failure. It is now the second most common cause of liver failure requiring transplantation in the United States.

“These products are no longer considered safe by FDA and have been voluntarily withdrawn” by the manufacturers, the FDA said. Or maybe not, because the FDA does not usually have to repeat itself.


Just four months ago, the agency called on doctors, dentists and pharmacists to stop recommending or writing prescriptions for drugs such as Vicodin and Percocet that contained more than 325 milligrams of acetaminophen.

Over the years, the acetaminophen dose in formulations of opiate pain relievers had crept up to 600 milligrams and even 700 milligrams, because it was thought to enhance the effectiveness of the opioid medication and make it less addictive, said Shelley Ducker, director of the Consumer Healthcare Products Assn’s Education Foundation.

But the FDA now believes that such high doses have demonstrated no superiority over lower doses, and that they pose dangers to the liver, especially because patients sometimes also take over-the-counter acetaminophen as well.

The voluntary withdrawal does not affect over-the-counter medications, and pharmacy shelves remain stocked with “extra-strength” over-the-counter acetaminophen (500 milligrams) for pain relief, as well as over-the-counter stalwarts as Benadryl, Excedrin, Nyquil, Robitussin, Theraflu and Vicks. And many surgeons and dentists continue to recommend these medications to patients.

Because acetaminophen has become a workhorse of our home medicine chests, it bears repeating that it may also sometimes be contained in prescription drugs we take home from dental and hospital procedures.

To ensure that those prescription medications contain only the lower dose, the FDA said pharmacists should remove the product codes for prescription medications containing more than 325 milligrams of acetaminophen from their automatic reordering systems. When patients come to fill prescriptions for products containing more than 325 milligrams of acetaminophen, the FDA recommends that pharmacists call the prescriber to discuss a lower dose.


As explained by Harvard Medical School’s Family Health Guide, most acetaminophen is broken down into harmless substances that are removed from the body in urine. However, “a small percentage is rendered into a compound that’s extremely harmful to cells,” the guide says.

The compound is known by the acronym NAPQI, and it’s combined with an antioxidant called glutathione to make it safe to ingest. In the case of an overdose, there’s “not enough glutathione to sop up NAPQI,” making liver damage a threat, the guide says.

[For The Record, 12:25 p.m. PDT April 29: An earlier version of this post did not note that the repeated warning by the Food and Drug Administration applies only to prescription medications containing high doses of acetaminophen. “Extra-strength” acetaminophen -- 500 milligram pills, capsules or caplets purchased over the counter --has not been recalled, and remains legally available. Over-the-counter combination medications are also not affected by the FDA’s warning.]