What is the maximum safe daily dose of acetaminophen and why?

The maximum recommended daily dose of acetaminophen is 4,000 milligrams for healthy adults, though many guidelines now suggest a lower maximum of 3,000 milligrams to reduce liver damage risk. Exceeding the maximum dose causes hepatotoxicity because a toxic metabolite called NAPQI overwhelms the liver's glutathione stores. Acetaminophen overdose is the leading cause of acute liver failure in the United States. The antidote is N-acetylcysteine, or NAC, which replenishes glutathione.