In today’s world, acetaminophen is a remarkably popular over-the-counter drug. Most commonly known as paracetamol in many countries, this drug is classified as an analgesic (pain reliever) and an antipyretic (fever-lowering drug). However, as with any other drug, you need to know exactly how acetaminophen works, when it is indicated, as well as how to avoid its side effects and toxicity.

Brief History of Acetaminophen

A derivative of coal tar, acetaminophen or paracetamol belongs to a class of drugs called “aniline analgesics”; and is the only drug known as such that’s still in use. It is in fact, the active metabolite of phenacetin, a well-known analgesic and antipyretic in the past; however, unlike phenacetin and its combinations, paracetamol is not known to cause cancer at therapeutic levels. The names paracetamol and acetaminophen are both derived from the chemical name of the compound para-acetylaminophenol. In certain contexts, this compound is simply called APAP, an abbreviation for N-acetyl-para-aminophenol. In this article, acetaminophen and paracetamol are used interchangeably, but since the title bears the name acetaminophen, this name will be used more often here than paracetamol.

In the United States, acetaminophen gained FDA approval in 1951 and was first distributed by Sterling-Winthrop Co. in 1953. The company promoted the drug as preferable to aspirin since children and people with ulcers could take it safely. Tylenol, the most popular acetaminophen brand in the U.S. was launched in 1955 by McNeil Laboratories which began to market acetaminophen under the brand name Tylenol Children’s Elixir, a pain and fever medication for children. Like acetaminophen and paracetamol, the word Tylenol also came from para-acetylaminophenol.

In 1956, Frederick Stearns & Co., a Sterling Drug Inc. subsidiary, produced 500 mg paracetamol tablets and marketed as Panadol in the United Kingdom. Panadol was initially a prescription drug for pain and fever relief, and was promoted as being “gentle to the stomach” unlike other analgesics available during that time. Paracetamol was incorporated to the British Pharmacopoeia in the year 1963, and has become very popular since then as a pain reliever with less side effects and little drug interaction with other pharmaceutical agents. But safety issues regarding paracetamol use prevented it from gaining widespread acceptance until the 1970s. Then in the 1980s, the sales of paracetamol went beyond those of aspirin in many countries, including the United Kingdom. This, together with the demise of phenacetin in the market due to analgesic nephropathy and hematological toxicity attributed to it, made paracetamol even more popular.

Since the expiry of paracetamol patent in the U.S. several years ago, many generic versions of the drug have emerged under the Drug Price Competition and Patent Term Restoration Act of 1984. However, certain preparations of Tylenol remained protected until 2007.

Mechanism of Action

Although it is not exactly known how acetaminophen works, experts believe that this drug alleviates pain by increasing the person’s pain threshold, the level by which the individual feels pain. When pain threshold is elevated, pain would have to be greater for a person to feel it.

As a fever-lowering agent (antipyretic), acetaminophen acts on the area of the brain that regulates body temperature. It particularly orders the brain’s thermoregulation center to lower the temperature when it is elevated.

Other Uses

Although primarily indicated for the relief of fever and mild aches and pains, acetaminophen can also be used to treat pain due to mild arthritis. However, since this drug does not have an antiinflammatrory action, it does not relieve any forms of inflammation, swelling and redness. But acetaminophen is as effective as aspirin in relieving pain that is not due to inflammation.

Available Preparations

Acetaminophen is an over-the-counter drug that comes in various forms. It is available as chewable tablets, coated caplets, gelcaps, geltabs, liquid suspensions, and even suppositories.

Interactions with other drugs

Since acetaminophen undergoes metabolism in the liver, drugs that enhance the action of liver enzymes that break down acetaminophen can therefore lower the therapeutic levels of the drug. This can in turn reduce the therapeutic effects of acetaminophen. Drugs known to increase the action of liver enzymes include carbamazepine (Tegretol), and antituberculosis drugs isoniazid (INH, Nydrazid, Laniazid) and rifampin (Rifamate, Rifadin, Rimactane). Acetaminophen doses greater than recommended amount can cause toxicity to the liver and may lead to severe liver damage. This potential toxic effect of this drug in the liver is heightened when combined with alcohol or drugs that are also harful to the liver.

The intestinal absorption of acetaminophen is reduced by cholestyramine (Questran). This can lower the effects of acetaminophen. To avoid this, acetaminophen must be given 3 to 4 hours after cholestyramine or an hour prior to cholestyramine administration.

Acetaminophen may also enhance the blood thinning action of warfarin (Coumadin), when daily doses exceed 2,275 mg. It is therefore imperative to avoid administration of large acetaminophen doses during the course of warfarin treatment.

Precautionary Considerations

Most drugs are not safe to be taken during pregnancy. But women in all stages of pregnancy can take acetaminophen safely. In fact, it is the treatment of choice for short-term fever and minor aches and pains during pregnancy.

The use of acetaminophen in nursing mothers appears to be safe too, although the drug is passed into the breast milk in small quantities.

Side effects of acetaminophen                                    

When used properly, acetaminophen rarely causes any side effect. However, this drug can cause liver damage when taken in excessive quantities. This serious adverse effect can also result when acetaminophen is used over a prolonged period, or simultaneously with alcohol or other drugs harmful to the liver. Chronic alcohol intake may further increase the risk of bleeding in the stomach.

Final Thoughts

Due to its efficacy in treating fever and minor pain; coupled with its safety in children and pregnant women, acetaminophen or paracetamol can be considered as one of the greatest discoveries in the field of medicine and pharmacology. And the convenience of getting it without prescription is indeed something to be appreciated. We simply ought to be responsible in its use to maximize the benefits while avoiding its harmful side effects.