I could hardly believe my ears. At a recent work function, a colleague asked me if I’d heard about a plan to combine acetaminophen with an antidote to prevent acetaminophen overdose. I’d heard nothing about this, but we both agreed it sounded like an idea whose time was well overdue.
As I’ve noted in several e-Alerts (most recently in “Safety Measured” 12/29/05), the FDA estimates that there are more than 14,000 unintentional overdoses of acetaminophen every year, with about 100 of those cases resulting in death. Acetaminophen is the active ingredient in more than 200 over-the-counter painkillers, fever-reducers and cold medicines, including Tylenol.
When my colleague e-mailed the information she’d found in New Scientist magazine, I was in for another surprise. It stated that the British Technology Group (BTG) had spent five years unsuccessfully trying to make the new drug combo available. Then I checked the date of the article: 1990.
Coaxing the enzyme
Amazing but true: For two decades, a safer, potentially life-saving form of acetaminophen has been ready for market. The New Scientist article states that BTG scientists combined paracetamol (the UK name for acetaminophen) with an amino acid that acts as an antidote for paracetamol poisoning.
Hmm. An amino acid? That wouldn’t by any chance be N-acetylcysteine (NAC), would it? As I’ve mentioned in other e-Alerts, NAC is an amino acid that stimulates production of glutathione, a potent antioxidant enzyme that provides excellent protection against toxicity in the liver. Studies have shown that NAC is an effective antidote for acetaminophen poisoning.
After doing a little digging, I found some more detailed information in a BTG annual report from 2004. That year, BTG completed a license agreement for a product called Paradote, a painkiller (available only in the UK) that combines paracetamol with methionine, an amino acid. The report reads: “The presence of methionine maintains glutathione levels in the liver, which helps minimize liver damage if an otherwise fatal overdose is taken.”
It’s not NAC, but apparently close enough.
So why did it take this product the better part of 20 years to finally break through to the marketplace? One word: expense.
According to an analysis in QJM: An International Journal of Medicine, the cost of Paradote is more than six times higher than generic acetaminophen. So put the two products on the shelf, side-by-side, and not many people are going to choose the safer, more expensive product.
Also, as I mentioned above, more than 200 over-the-counter medications contain acetaminophen, and most overdoses occur when two or three of these medications are used at the same time. Given the extra expense, it’s unlikely that drug manufacturers would produce Paradote formulas for all these drugs.
But even though we’re a long way from a simple antidote-added solution to the acetaminophen overdose problem, there is a way that Paradote might be put to good use: by stocking the drug in hospitals.
In the e-Alert “Flick of the Wrist” (1/19/04), I told you about a young Philadelphia man named Marcus Trunk who took acetaminophen for several days in 1995 after spraining his wrist. When he developed a fever and began vomiting, he went to a hospital emergency room where doctors thought he had the flu and gave him further doses of acetaminophen. Within a week, Marcus died of liver failure caused by acetaminophen overdose.
If hospitals maintained supplies of Paradote, they could give it to patients instead of acetaminophen to avoid unintentional overdoses. There’s no way of knowing, of course, if this would have saved Marcus Trunk’s life, but it certainly could have given him a better chance.
You can find more information about acetaminophen dangers at the web site maintained by Marcus Trunk’s family: drug-warning.org.
“Tragedy Highlights Case for New Paracetamol Drug” Barry Fox, New Scientist, 7/28/90, newscientist.com
“BTG Annual Report & Accounts 2004” btgplc.com
“Paracetamol Toxicity: Epidemiology, Prevention and Costs to the Health-Care System” QJM: An International Journal of Medicine, Vol. 99, No. 5, 2002, qumed.oxfordjournals.org