Drug Profile

Like aspirin, the painkiller acetaminophen (TYLENOL) reduces pain and fever. Unlike aspirin, it does not help the redness, stiffness or swelling associated with inflammation. Because of this, aspirin (EASPRIN, ECOTRIN, EMPIRIN, GENUINE BAYER ASPIRIN) is much more effective for treating the inflammation of arthritis.[2]

However, one advantage of acetaminophen over aspirin is that acetaminophen does not cause the stomach bleeding that aspirin can cause.

For this reason, doctors often prescribe or recommend acetaminophen to people who are likely to suffer from bleeding when they take aspirin. This includes most people taking blood-thinning drugs like warfarin (COUMADIN) or heparin, because although the combination of acetaminophen and blood-thinning drugs can cause bleeding, it appears to occur less commonly than with aspirin. Also included in this group are people who have ulcers, gout or bleeding problems such as hemophilia.

People who are allergic to aspirin often can take acetaminophen.

Using acetaminophen to treat a fever

In general, patients should not take anything to reduce a fever until the cause of the fever is known. It is rarely necessary to treat a fever. However, if a fever is having harmful effects or is causing extreme discomfort, it can be reduced with acetaminophen. When taking acetaminophen to reduce a fever, take it regularly every four to six hours, and stop taking it when the underlying problem is gone or has been controlled through other treatment.

Adverse effects

There is the potential for allergic reactions (swelling of the face, mouth and throat; difficulty breathing; itching; or rash) with acetaminophen.

Acetaminophen and pregnancy

A meta-analysis (a study that combines data from many other studies) found that there was an increased risk of childhood asthma when acetaminophen was used during pregnancy. Based on these results, the authors recommended further research to determine recommendations that should be considered when treating patients.[3]

In 2016, the International Journal of Epidemiology published an article showing a slight increase in the risk of childhood asthma when acetaminophen was used by mothers during pregnancy or by infants up to age 6 months.[4]

Headache

Frequent use of medication to manage headache pain may lead to a condition known as medication overuse headache (MOH). According to a review published in the August 2004 issue of the medical journal Lancet Neurology,[5] there now is substantial evidence that all drugs used for the treatment of headache can cause MOH in patients who are using drugs to treat their headache. Even simple painkillers such as aspirin and acetaminophen can induce MOH.

Patients experiencing MOHs should discuss with their doctors the important details of their headaches and, depending on their individual case, the type of withdrawal from the MOH-causing drugs that is best for them.[6]

Liver damage and liver failure

Acetaminophen can cause liver damage, which sometimes can be fatal. Research published in the December 2005 issue of the medical journal Hepatology found that the annual percentage of potentially fatal acute liver failure cases caused by acetaminophen rose from 28% in 1998 to 51% in 2003.[7]

Research published in 2006 in the Journal of the American Medical Association (JAMA) further supports this finding. The JAMA research showed that healthy medical study participants given the maximum approved daily dose of acetaminophen developed an early sign of possible liver damage.[8] The maximum recommended dose was then 4.0 grams (g) (4,000 milligrams [mg]) per day, equivalent to two extra-strength acetaminophen tablets taken four times per day. These results are of particular concern because the people in the study were not drinking any alcoholic beverages. When combined with alcohol, this dose of acetaminophen would have further increased their liver toxicity.

In 2021, a research study in Hepatology showing that use of acetaminophen at the recommended dose for four days or longer was associated with liver damage in patients who drank alcohol excessively (drinking at least two alcoholic drinks daily) or fasted (not eating for at least 24 hours).[9]

Acetaminophen overdose and idiosyncratic adverse drug reactions involving the liver have replaced viral hepatitis (inflammation of the liver) as the most frequent apparent causes of acute liver failure in the United States.[10],[11] Patients must be careful to examine the list of ingredients in their medications because many prescription and over-the-counter drugs contain acetaminophen, although this may not be apparent from the brand name. Patients have overdosed from unsuspected use of two different acetaminophen products.

Some drug safety experts, including Public Citizen's Health Research Group, have argued that measures including limiting over-the-counter package size and restricting the prescription of narcotic-acetaminophen combinations (or to separate the narcotic from the acetaminophen) may be necessary to reduce the incidence of acetaminophen-induced liver toxicity.[7]

Interactions with other drugs

Results published from a prospective, randomized, double-blind, placebo-controlled study of 45 patients found that acetaminophen (at a dose of 2-3 g a day, administered for 10 days) increased the anticoagulant effect of warfarin in stable patients treated with warfarin.[12] (See drug interaction warning at the top of this profile: “Increased Risk of Bleeding When Acetaminophen and Warfarin [COUMADIN] Are Taken Together.”)

Studies show ...

The Medical Letter on Drugs and Therapeutics published an article in which the authors looked at the effectiveness of acetaminophen in doses of 1,000 mg versus 650 mg in treating mild-to-moderate pain from such conditions as osteoarthritis and headache. According to the article, no published data showed that the 1,000-mg dose was more effective than the 650-mg dose.[13]

The British Journal of Clinical Pharmacology published an article on the risk of mortality and the unintentional overdose of acetaminophen. The data examined in the study showed that the unintentional overdose of acetaminophen in patients was associated with severe acute (sudden) liver injury.[14]

In 2015, a meta-analysis combining data from 13 randomized clinical trials published in The British Medical Journal showed that acetaminophen had a small and short-term effect in patients with osteoarthritis of the hip or knee, but was ineffective in patients with low-back pain.[15]

In 2016, the Cochrane Database published a review showing that acetaminophen was no more effective than a placebo in treating patients with acute low-back pain and did not improve quality of life or physical function.[16]

In 2016, the Journal of the American Medical Association — Pediatrics (JAMA Pediatrics) published an article showing an increased risk of behavioral problems in children when acetaminophen was used during pregnancy.[17]

Regulatory actions surrounding acetaminophen

2009: On June 29 and 30, the Food and Drug Administration (FDA) held a public advisory committee meeting to address the concerns of liver injury in relation to the use of acetaminophen in both prescription and non-prescription products. The FDA considered the recommendations made by the advisory committees in order to demand interventions and take additional steps to reduce the number of cases of acetaminophen-related liver injury.

2011: In January, the FDA issued an advisory concerning the strength of acetaminophen in prescription-drug products. The FDA requested that drug manufacturers limit the strength of acetaminophen in prescription-drug products to 325 mg per tablet. The agency required a black-box warning be added to the drug label of all acetaminophen-containing prescription products that would highlight the potential for severe liver injury. The agency stated that another warning highlighting the potential for allergic reactions (swelling of the face, mouth and throat; difficulty breathing; itching; or rash) would also be added to the drug label. The makers of TYLENOL have recommended reducing the maximum daily dose of acetaminophen from 4 to 3 g.[18]

2013: In August, the FDA issued an advisory that acetaminophen was found to be associated with a risk of rare but serious, potentially fatal skin reactions, such as Stevens-Johnson Syndrome. According to the advisory, the skin reactions can occur at any time after starting treatment with the drug.[19]

2014: In January, the FDA issued another advisory on the dosage of acetaminophen. The FDA recommended the discontinuation of prescribing and dispensing of prescription combination drug products that contain more than 325 mg of acetaminophen per tablet. There are no available data to show that taking more than 325 mg of acetaminophen per dosage unit provides additional benefits that outweigh the added risks for liver injury.[20] Unfortunately, the FDA has not yet ordered the reduction of the more widely used over-the-counter versions of acetaminophen from 500 mg to 325 mg.