common OTC drug, narrow “safety margin”
The U.S. Food and Drug Administration (FDA) will be considering later this month, at a meeting in Maryland, new restrictions on the labeling and strength of the pain-reliever acetaminophen (known internationally as paracetamol; the most famous brand is Tylenol). Studies show most consumers are unaware of the risks of the drug. It is not a bad medication—it can be a wonderful alternative to aspirin—but you need to be extra cautious with its use…let’s discuss why.
Drugs can be classified as to their “safety margin”, which refers to a comparison of the dose of a drug needed to be therapeutically effective compared with the amount of the drug needed to produce toxicity. Some drugs, for example, penicillin, are considered to have a rather wide safety margin because a relatively small dose of these drugs can be therapeutically effective (here, cure an infection), but normally you need a very large dose to get serious toxicity.
On the other side of the safety margin scale are drugs like acetaminophen, which have a NARROW margin of safety, meaning, the difference between a normal therapeutic dose and a dose that will produce toxicity or even death is relatively small (“narrow”). So you need to be extra careful when taking a drug with a narrow safety margin, like Tylenol. Overdosage is common, and serious Tylenol overdosages are NOT easy to treat or reverse. Sometimes the only treatment is a liver transplant. Milder overdoses that occur over a period of time might not even be recognized by the patient, but result in chronic liver damage.
Shockingly, acetaminophen overdosage is the “leading cause of acute liver failure in the United States”. Meaning this drug is worse than alcohol for causing acute liver failure (note that “acute” in a medical sense does not mean serious, rather, acute means a condition that arises or appears over a very short period of time).
Severe liver damage from this OTC drug can occur from a dose that you might not consider excessive. A person who already has some level of liver problem—for example from chronically drinking too much alcohol—can suffer irreparable liver damage from taking only four or five 500 mg. tablets over one 24 hour period.
Currently, the maximum safe dose (as listed on the product label) is 4000 milligrams per day, meaning: a maximum of two-500 mg. “extra-strength” tablets every 6 hours for a day. But…how often do you think this dose is exceeded, if not by you, by others in pain who, rather than wait 6 hours between doses, take a new dose after only, say, 4 hours? It’s happens a lot.
So at the FDA meeting later this month, the group will consider a recommendation to lower the maximum daily dose from 4000 mg. to 2600 mg., and cut the size of the biggest allowable tablet from 500 mg. to 325 mg. No matter what they decide, take caution with this drug, especially if you already have any liver disease, have elevated “liver enzyme” blood levels, take statin drugs to lower cholesterol, or you drink a moderate or greater amount of alcohol daily. It’s not clear at what level of daily alcohol use you have to be concerned; the Tylenol label says to “ask your doctor if you drink more than 3 drinks per day”, but many experts believe if you drink less than that you should be extra careful with acetaminophen.
Your physician should be able to answer any questions about your liver function with some simple blood tests, and if you have concerns about your daily alcohol intake combined with acetaminophen. For everyone however, even those who drink rarely, if you “binge”—drink significant alcohol at any one time—don’t use acetaminophen to try to treat a headache or hangover (however aspirin is not great either, because it can irritate the stomach).
Be aware that acetaminophen (or paracetamol or APAP as it is known in some countries), is not only found in the Tylenol brand, but is a component of many other common OTC medications… over 200 formulations contain acetaminophen but don’t carry the Tylenol label, and the presence of acetaminophen is only discovered by reading the fine print on the back. Consult this list for examples; and better, read the ingredients of every pain or anti-fever medication you take to see what’s inside. You might take Tylenol in the evening, then at bedtime take a slug of, say, Nyquil, not realizing it too contains the same drug.
I will let you know what the FDA decides after their meeting at the end of June, but for an interim FDA report, with more details about acetaminophen, click here (pdf).
In summary, acetaminophen can be a wonderful drug, but with a narrow “safety margin”, it deserves special caution.
