Monday, December 12, 2005

No Tylenol for a bon vivant

Pop quiz: what is the leading cause of acute liver failure in the US?

Answer: Tylenol (acetaminophen).

This has been known for a few years, but the general public (and many health care providers) remain unaware of it. The "therapeutic window" (the difference between a safe and harmful dose) is narrow and the drug is found in many different formulations (an estimated 200), often labeled non-aspirin pain relievers. Thus it is relatively easy to take several different over-the-counter and even prescription drugs (e.g., Percoset and Vicodin) that have acetaminophen in them and exceed the maximum recommended daily dose of 4 grams/day (8 pills, each with 500 mgms; i.e., two maximum strength tablets four times a day). It is thought that as little as 7.5 grams (less than double that) might result in severe liver injury in some people. (MedPageToday, reporting on a recent paper by Larson AM et al "Acetaminophen-Induced Acute Liver Failure: Results a United States Multicenter, Prospective Study." Hepatology 2005;42:1364-1372.)

While liver toxicity is still relatively rare compared to the estimated 8 to 9 billion tablets ingested annually in this country, marketing practices make it more likely to happen. For one thing, the drug is aggressively marketed as being an especially safe analgesic compared to aspirin. It is true its gastric effects are less, but the liver toxicity is more severe. In addition, it is sold in a Regular Strength (325 mg) and Extra Strength (500 mg) formulation, with the lower dose receiving significantly less room on the drugstore shelf, according to the American Liver Foundation. Others have noted that the bulk containers ("like M&Ms") also contribute to the problem. They suggest either putting the tablets in blister packs or restricting the amount that can be purchased at one time:
Both the study authors and editorialist [Dr. John G. O'Grady] suggested that a strategy restricting but not banning over-the-counter sales of acetaminophen containing medications may be necessary to prevent accidental overdoses.

"This approach was taken in the United Kingdom in 1998, when over-the-counter sales of acetaminophen were restricted to 16 g," he wrote. "In the four years following the change in legislation there was a 30% reduction in patients with severe acetaminophen-induced acute liver failure admitted to specialist liver units and liver transplant centers."

In France, where only half that much acetaminophen can be bought at one time "this measure is highly effective in minimizing severe acetaminophen hepatotoxicity," Dr. O'Grady added. (MedPageToday)
Good idea, but probably a non-starter in this regulatory climate. The FDA won't stop bacterially contaminated and fraudulently marketed snake oil cures. What's the likelihood they will try to regulate the sale of a drug that is in 200 different products and a major money maker for Big Pharma?

That was a rhetorical question.

Addendum: It has been called to my attention that the little bilingual pun in the post title is, shall we say, a bit too obscure. Here's the explanation: a literal translation of the French idiom bon vivant is "good liver."