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An acceptable risk?
by Randy Drake


here is a concept in medicine called the “risk/benefit ratio.” This states that, in general, the risk (side effects) of a medication must be proportionate to its benefit (therapeutic effect). If a certain drug cures a woman’s breast cancer but makes her hair fall out, that is considered an acceptable risk. If a drug cures a man’s prostate cancer but makes him impotent, that is considered an acceptable risk. But it would be completely unacceptable for an acne cream to cause a woman’s hair to fall out or an athlete’s foot spray to render a man impotent.

Suppose there were a medication whose side-effects:
  • cause of 42% of cases of acute liver failure
  • increase the risk of hypertension by 90%-400%
  • double or triple the odds of end-stage renal failure
  • cause 50,000 emergency room visits per year
  • kill about 500 people per year

What provable therapeutic benefit would be necessary for the FDA to approve a medication with such serious side-effects? Might such a drug cure cancer? Increase survival rates after a heart attack? Prevent reperfusion injury following a stroke? Relieve a headache? Bring down fever?

If you said, “Relieve a headache and bring down fever,” you’d be right. The killer drug that generates all of the statistics listed above, and which is probably in your very own medicine cabinet, is acetaminophen. Tylenol is the largest-selling brand of acetaminophen, but it can be found in over 400 other OTC meds and more than 100 prescription drugs.

How prevalent is acetaminophen use? A 2002 survey found that 1 in 5 adults in the U.S. take it for pain or fever each week. Add to that the number taking it in OTC combination products, such as cold and flu meds, and those taking prescription pain meds that contain acetaminophen, such as Vicodin, Percocet, and Darvocet.

Acetaminophen is the most common cause of acute liver failure, according to a report in the journal Hepatology. You’ll cause severe liver damage by taking only double the suggested maximum dose of 4000 mg/day. (The scientific proof of that statement is in stark contrast to the FDA’s bogus evidence of ephedra’s harmfulness, in which they had to find examples of people taking 4 to 20 times the recommended daily dose of ephedra to “prove” that ephedra is harmful! The court was not kind to the FDA’s attempt to make an end-run around the law.)

Some 44% of acetaminophen overdose cases are suicide attempts, but 48% of acetaminophen-related liver failures are from unintentional overdose, which is not difficult...

Say you take Tylenol Cough & Sore Throat Daytime every 6 hours for your cough & sore throat. But you also have a stuffy head and overall achiness from the flu, so you add something for those symptoms, perhaps Theraflu Severe Cold Non-Drowsy, which you also take every 6 hours as directed. Because both of these are “nondrowsy,” “daytime” formulations, you want to take something to help you sleep. A single dose of NyQuil just before bedtime ought to do it. Congratulations! You just dumped 9000 mg of acetaminophen into your body that day. Less than one week on that regimen buys you a trip to the ER and possibly a spot on the liver transplant list!

“All substances are poisons; there is none which is not a poison. The right dose differentiates a poison and a remedy.” —Paracelsus

OTC medications are not the only problem. Vicodin is the most popular prescription drug in the United States. Tim Davern, MD, a liver transplant specialist at the UCSF Medical Center, said, “I think the practice of combining acetaminophen and an opiate, such as hydrocodone bitartrate, together as a single drug (as Vicodin does) defies logic, if not common sense. Acetaminophen is a potent dose-dependent poison for the liver; simply stated, if you take too much, your liver dies. On the other hand, opiates, such as hydrocodone bitartrate and codeine, while safe for the liver, are highly addictive. Some patients become addicted to the opiate component of Vicodin and consume increasing amounts of acetaminophen, ultimately leading to acute liver failure.” Dr. Anne Larson of the University of Washington Medical Center tells of an 18-year-old whose liver died after using Vicodin for three or four days for car-crash injuries. “She was just taking too much because her pain was bothering her.”

McNeil, the maker of Tylenol, is running an ad campaign that ends with the tag line, “If you’re not going to read the label, then don’t buy our products.” That attitude is not surprising. A jury recently awarded a Philadelphia family $5 million for the death of their 1-year-old son, who died of acetaminophen toxicity after receiving Infants’ Tylenol. This award came even though parents ignored label directions which said not to give the product to a child under two years except as directed by a physician. The parents gave the child two droppers every 4 hours, and he died three days later.

Even at the recommended dosage, acetaminophen is not safe. While some people continue to pop them like M&Ms for headaches, muscular aches, and other minor pain, researchers were conducting a study of healthy adults taking just 4000 mg/day — the recommended maximum dosage. The test was designed to show interactions between acetaminophen and various opiates.

This study, published in the July 5, 2006, Journal of the American Medical Association, stated that after two weeks, 40% of the nonplacebo study participants had abnormal changes in lab tests that signaled liver damage. When the liver tests came back abnormal, they stopped the opiate part of the trial. The researchers thought they would find the problem as an interaction between hydrocodone and acetaminophen. “Our jaws dropped when we got the data,” one researcher said. “It doesn’t have anything to do with the opiate. [The problem is] good ol’ garden-variety acetaminophen.”

Most over-the-counter medications voluntarily list the acetaminophen content on their front label. Some even warn of the hazards of overdose. But the warning, if present, varies by product. In 2002 the FDA’s scientific advisers proposed a rule to standardize such warnings. In 2006, four years (200,000 ER visits and 2000 deaths) later, the FDA is still “considering the proposal.”

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