DALLAS — N-acetylcysteine for acetaminophen overdose is one of the best antidotes in all of poison control medicine—provided it's given within the right time frame, Dr. Carson R. Harris said at the annual meeting of the Society of Hospital Medicine.
“This is a great antidote. It's virtually 100% effective if given within 8 hours. That's your key, that 8-hour window. A patient can take 3 pounds of acetaminophen—I've had one who tried—and if you start NAC [N-acetylcysteine] within 8 hours they'll still probably be okay,” said Dr. Harris, director of the toxicology section at Regions Hospital, St. Paul, Minn.
Acetaminophen is one of the most common causes of overdose. That's because acetaminophen is present in more than 200 over-the-counter and prescription drug products, including a plethora of cold and allergy medications.
“We get an acetaminophen level on every altered-mental-status patient who comes in,” he said.
Liver damage can occur in adults who take 150 mg/kg of acetaminophen. The hepatotoxicity risk is increased in alcoholics, patients on hepatic enzyme-inducing medications, and in those older than age 45 years.
A serum acetaminophen level of 150 mcg/mL at 4 hours post ingestion warrants NAC therapy. NAC protects the liver and reduces the risk of cerebral edema. It is a free-radical scavenger that binds and neutralizes acetaminophen's toxic metabolite, increases glutathione synthesis, and improves hepatic microcirculation.
NAC is approved by the U.S. Food and Drug Administration in both oral (Mucomyst) and intravenous (Acetadote) forms for the treatment of acute overdoses.
The advantages of Acetadote are that it's well tolerated and can be given in a 20- or 48-hour protocol, whereas oral NAC smells like rotten eggs and is approved as a 72-hour treatment regimen.
However, Dr. Harris and other poison control experts use an abbreviated oral NAC schedule that gets most patients out of the hospital in 24 hours. It entails a 140-mg/kg loading dose followed by 70 mg/kg maintenance doses given every 4 hours.
“If the patient is not pregnant and doesn't have any other factors that may cause increased toxicity, you can actually stop treatment after 24 hours if at that point the acetaminophen level is less than 2 mg/L and transaminases are less than two to three times the upper limit of normal. That's what we do. We almost never have patients who take a Tylenol overdose stay in the hospital for 72 hours if they get NAC within 8 hours,” Dr. Harris continued.
Oral NAC comes in a 20% solution that should be diluted to 5% in juice or soda. The sulfur odor is a real problem; antiemetic therapy with metoclopramide (Reglan) or ondansetron (Zofran) is often necessary.
Dr. Harris stressed that there's nothing magic about the 20-, 24-, 48-, or 72-hour treatment cutoffs.
“If your patient still feels sick and the liver enzymes are going up, it usually means you got treatment started late. You may have to continue treatment for another 20 hours or so,” he explained.
The wholesale cost of enough generic NAC for 24 hours of oral therapy in a 70-kg patient is $18, compared with $430 for Acetadote.