The dark side of acetaminophen
Acetaminophen’s death toll is also tiny considering the billions of tablets taken every year. In 2008 alone, manufacturers sold an estimated 4.1 billion doses to Canadian hospitals and pharmacies, according to a Health Canada report. In 2012, hospitals and pharmacies purchased $122.6 million worth of acetaminophen, according to health information company IMS Brogan. Last year, Canadians spent $148 million buying the drug from retailers and pharmacies, according to market research firm Nielsen.
But acetaminophen is older than today’s regulatory standards - it was first used as medicine in 1893 and became widely available in the early 1950s.
If it entered the market today, it probably would not be approved as an over-the-counter drug. Even in 1975, an editorial in the leading medical journal The Lancet stated that, had acetaminophen been introduced that year, it “would not be approved by the (British) Committee on Safety of Medicines and it would certainly never be freely available without prescription.”
“Toxicity can result in death or transplant - it’s not just fevers or a day off work,” noted Dr. Paul Marotta, head of the liver transplant unit at London Health Sciences Centre in London, Ont. “So that would be a product that would probably have a very strict indication, would not be over-the-counter.”
Acetaminophen is a very safe drug when taken at recommended doses. But many people don’t take it at such doses. The sheer ubiquitousness of the stuff makes many consumers overlook its dangers.
Here’s a Closer Look at acetaminophen:
How does acetaminophen damage the liver?
The liver’s job is to process foreign substances, such as medicines, which are broken down and cleared from the body.
Acetaminophen goes through two metabolic pathways: In one, the drug molecules in the bloodstream are fitted with molecular tags - sugars or sulfates - that allow them to be easily removed from the body in the bile, says Dr. Kennon Heard (no relation to Stuart Heard), physician with the Rocky Mountain Poison and Drug Center in Colorado. The other metabolic process converts the drug into what Heard calls “activated acetaminophen,” which is toxic to liver cells.
With typical doses of acetaminophen, 90% of the drug is processed via the first, safe pathway and less than 5% is activated into toxic form. (About 5% of acetaminophen is excreted unchanged through the urine.) With high doses, however, the safe pathway can’t keep up, the liver ends up making more poisonous byproduct, and injury occurs.
American drug regulators have expressed concern with the drug’s “narrow therapeutic window,” as recently reported by investigative journalism centre ProPublica - meaning the dose that damages is relatively close to the dose recommended on your pill bottles. ProPublica recently reported on issues surrounding acetaminophen in the U.S. and aided the Star on this story.
“With acetaminophen you have a drug that is virtually spotless when used as directed,” said Gerry Harrington, director of public affairs for Consumer Health Products Canada, a drug industry group representing large over-the-counter drug and natural health product makers.
“But there’s a sharp veering into danger if you’re reckless with it. It is, in that respect, a real standout.”
As the drug’s popularity grows - dosages bought by hospital and drugstores grew by 26 per cent between 2004 and 2008, according to a Health Canada report - so does the potential for error.
More than a third of Canadians misused over-the-counter drugs, according to a 2004 survey commissioned by Health Canada. Seventy-five per cent of consumers and even health professionals also considered non-prescription drugs to be “generally, if not completely, safe,” the survey found.
Deaths are just one piece of the problem.
“That’s only the tip of the iceberg,” said gastroenterologist, liver specialist and intensive care physician Dr. Constantine Karvellas with the University of Alberta, who is researching acetaminophen. “If you look at it as a societal problem, it’s a much bigger issue.”
The next layer down would be the acute liver failures - a rare, sudden and often fatal condition that frequently requires a liver transplant. Karvellas has treated more than 50 cases of acute liver failure over the last three years - 60 per cent caused by acetaminophen.
More common are hospitalizations for acetaminophen-induced liver injuries, which can often be treated with a very effective antidote, one that McNeil helped develop. Across Canada, acetaminophen overdoses were linked to 10,340 emergency room visits between 2009 and 2012, according to data from the Canadian Institute for Health Information (CIHI). The same time period saw nearly 13,000 hospitalizations - to the tune of an estimated $43.3 million.
There are untold numbers of overdoses that never get treated or reported. People may call one of Canada’s five poison control centres - in 2012, they answered more than 23,000 calls about acetaminophen, according to data provided by the centres.
The calls range from the relatively minor (a mom worried about her baby swallowing an acetaminophen pill) to the serious (suicide attempts). In Alberta, Saskatchewan and Quebec, more people are calling about unintentional overdoses than intentional ones, the data shows.
“Acetaminophen is by far and away the most common medication or drug-related call that we receive at our poison centre,” said Dr. Mark Yarema, the Alberta poison centre’s medical director. “That’s all age groups - so from pediatrics all the way up to seniors.”