Acetaminophen (Tylenol): What Is a Safe Dose When You Drink Alcohol Regularly?

The recent news that an FDA advisory panel has proposed that Vicodin and Percocet be taken off the market because of their acetaminophen content has prompted a discussion about the overall safety of this drug, which is best known as Tylenol and is present in a number of both prescription and over-the-counter pain drugs.

The New York Times’ Tara Parker-Pope had a good summary in her Well blog, in which she said acetaminophen is generally safe when taken within the maximum dosing guidelines of no more than four grams — 4,000 milligrams or 8 extra-strength tablets — per day. But there is one big exception that she didn’t discuss: for people who regularly drink alcohol, the daily limit of acetaminophen should be much lower. I explained this in a comment to her blog entry. Here is the text of what I posted:

The link between acetaminophen and alcohol deserves to be clarified because it is not that straightforward but is actually pretty easy to understand. Regular alcohol drinking “induces” a metabolic pathway in the liver called P-450 2E1, making the liver more efficient at breaking down alcohol with this 2E1 enzyme. This happens within a few days of drinking 2 or 3 or 4 drinks a day. That’s why steady drinkers can “hold” their liquor better, because they are breaking it down faster and so less alcohol gets in the blood. When you stop drinking for a few days, the liver reverts back to its old self and so the first time you drink again, your liver is less efficient at breaking down the alcohol so you get a “buzz” with the first drink. Here’s how this relates to acetaminophen: The same 2E1 enzyme turns acetaminophen into the toxic byproduct (called NAPQI) that can destroy the liver. So regular drinking produces more 2E1 and hence more NAPQI, and the more acetaminophen you take, the more the NAPQI can overwhelm the liver’s other defense mechanisms and cause liver cell death. But here’s the twist: drinking alcohol at the same time as you take acetaminophen puts both drugs into the liver at the same time, competing for the same 2E1, and thus drinking at the same time actually can protect against liver damage. The deadly pattern is when a drinker gets sick, with the flu for instance, stops drinking and starts taking acetaminophen near the maximum 4 grams a day, and that can cause catastrophic liver failure (because the 2E1 has nothing else to do but turn the acetaminophen into the NAPQI). I know about this because as a lawyer I represented a number of Tylenol victims in lawsuits in the mid-1990s that helped get the alcohol warning onto acetaminophen labels. I took many depositions of the medical people at McNeil, the Tylenol manufacturer.

Anyone who drinks regularly should take no more than 2 grams of acetaminophen a day. Any liver specialist will tell you that.

I talk about what I call the safe and skeptical approach to taking medicines in my new book: “The Life You Save: Nine Steps to Finding the Best Medical Care – and Avoiding the Worst.”

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