Acetaminophen vs. NSAIDs: Everything You Need to Know

Pain relievers, also known as analgesics, come in many forms, including NSAIDs, COX-2 inhibitors, acetaminophen, antidepressants, and opioids. Some of these are available over-the-counter without a prescription. Researchers classify these medications based on the chemical reaction the medications trigger to relieve pain.

NSAIDs (nonsteroidal anti-inflammatory drugs) like Advil or Motrin reduce inflammation by blocking certain inflammatory cyclooxygenase (COX) enzymes. While inflammation promotes clotting, it also results in pain and sometimes fever. NSAIDs reduce pain by inhibiting the action of these enzymes, thereby preventing the production of a hormone called prostaglandin (1). Unfortunately, taking NSAIDs in excessive quantities over a long period of time can lead to stomach ulcers, nausea, or, in severe cases, kidney disease, in addition to certain cardiovascular complications.

Another class of analgesic, known as COX-2 inhibitors, also reduce inflammation and fever. They constitute a special subclass of NSAIDs that block only one type of COX enzyme as opposed to two types of COX enzymes. This reduces gastrointestinal side effects, which are important to consider for people who have weaker digestive systems (2). Some examples of COX-2 inhibitors include celecoxib (Celebrex), rofecoxib (Vioxx), and amlodipine (Consensi). COX-2 inhibitors can cause ulcers, bloating, diarrhea, nausea, or vomiting. Like other NSAIDs, COX-2 inhibitors can negatively impact the cardiovascular system. Some in this category have such elevated risks for cardiovascular complications that the Food and Drug Administration (FDA) has set extremely high standards for approval of these pain relievers.

Acetaminophen is yet another over-the-counter pain reliever. As we’ll see, its mechanism of action differs significantly from NSAIDs and COX-2 inhibitors. As a result, it's useful for different kinds of pain and offers a different side effect profile than other over-the-counter medications.

Acetaminophen has many names, including paracetamol and APAP. However, it’s probably best known by the brand name Tylenol. Doctors recommend using this pain medication to temporarily relieve minor aches, pains, minor arthritis pain, premenstrual and menstrual cramps, common cold pains, toothaches, and back aches. Acetaminophen also has antipyretic properties, meaning it can reduce fever.

It’s important to be careful with your acetaminophen dosage, as adverse effects can occur more easily with smaller doses of acetaminophen than with NSAIDs. Don’t take more than 3,000 mg/day, and don’t take the maximum dosage for more than two consecutive days. Acetaminophen is found in many other medications, such as Midol, Robitussin, and Sudafed, along with heavier drugs like Percocet, so make sure you read all ingredient labels and consult your physician before combining medications (3). Acetaminophen carries particularly strong side effects for the liver and can even cause liver failure in extreme cases. While it may be intuitive to think that taking pain relievers before drinking alcohol can prevent hangovers, this is in reality incorrect, and you shouldn’t mix acetaminophen or other drugs with alcohol (4).

While researchers know how NSAIDs and COX-2 inhibitors work, they still don’t understand the mechanism by which acetaminophen relieves pain (5).

Scientists initially thought that acetaminophen blocked a hormone in the central nervous system (6). Later, they came to believe that acetaminophen reacted with a new COX enzyme called COX-3 (7). This hypothesis was debunked, however, by the results of subsequent experiments with animals (8). Today, researchers believe that acetaminophen either activates certain ion channels in the brain and spinal cord or affects serotonin neurotransmission (9, 10).

Acetaminophen does not reduce inflammation, and so it doesn’t qualify as an NSAID. Although this is a limitation, acetaminophen also doesn’t irritate the stomach or intestinal lining, making it useful for controlling chronic pain in people who can’t tolerate NSAIDs.

Below, we’ve included a list of common brand names to look out for and avoid if you do have trouble tolerating NSAIDs:

• Naproxen (Aleve, Anaprox, Naprelan, Naprosyn)
• Ibuprofen (Advil, Motrin) 
• Aspirin (Bayer, Ecotrin) 
• Piroxicam (Feldene)
• Oxaprozin (Daypro) 
• Celecoxib (Celebrex)
• Diclofenac (Cambia, Cataflam, Voltaren-XR, Zipsor, Zorvolex)
• Indomethacin (Indocin) 

Acetaminophen and NSAIDs differ significantly in terms of which kinds of pain they’re best suited to treat.

Acetaminophen works best for treating conditions such as arthritis, body aches, fever, and minor aches, while NSAIDs like ibuprofen are better suited for bigger headaches, menstrual cramps, toothaches, minor injuries, and inflammatory pain. Unlike NSAIDs, acetaminophen doesn’t have to be taken with food.

Overall, NSAIDs relieve musculoskeletal pain more effectively than acetaminophen, but at the price of greater side effects (11). You should be careful with ibuprofen if you have heart disease, high blood pressure, clotting disorders, or kidney problems. If you’re pregnant, you should not use ibuprofen at all. On the other hand, acetaminophen is safe for pregnant women, but can lead to liver problems for anyone if used for too long. Both acetaminophen and NSAIDs can lead to complications if used chronically (12).

As long as you keep an eye on your daily limit of both NSAIDs and acetaminophen, and you have talked with your doctor, you can use these drugs as supplements. For example, if you have menstrual pain and don’t find relief from NSAIDs, you can try acetaminophen soon afterwards.

When to Take Acetaminophen

When it comes to pain relief, it’s tempting to jump straight to the most extreme measure you can access. However, in addition to carrying risks and side effects, these medications can be costly. It’s important to carefully assess your level of pain so you can figure out the proper next steps regarding pain management.

First, take note of important details about your pain. What part of your body does the pain radiate from? Is it dull, sharp, burning, tingling, or stinging? How long have you been hurting? Did your pain start suddenly or gradually?

Consider treatment approaches that don’t involve medication before turning to painkillers. The first-line treatment is always rest – whether that’s sleeping or just taking it easy. Try also applying a hot or cold compress where it hurts. If these pharmacological-free treatments don’t work, move on to OTC pain relievers like acetaminophen or NSAIDs.

Choose acetaminophen when your pain is mild. A study found that acetaminophen sometimes fails to outperform placebos in cases of acute lower back pain (13). NSAIDs like celecoxib provide better relief  overall for musculoskeletal pain than acetaminophen does, though acetaminophen does provide some relief (14). Acetaminophen may not effectively treat chronic pain conditions (15), though it can be a good choice for minor, short-term pain, given its reduced side effect profile.

If your pain persists longer than two weeks, causes stress, prevents sleep, or disrupts your daily activities, consult a healthcare professional. Your provider may prescribe prescription-strength NSAIDs, muscle relaxants, antidepressants, or in serious cases, opioids. Complement your prescription pain management with non-pharmacologic treatments such as massages, physical therapy, or stretching exercises. Record any observations of your pain and the effect of pain relievers. If you notice the pain doesn’t get better or it gets worse, your doctor may prescribe steroid injections or surgery.

How to Take Acetaminophen

Acetaminophen comes in many forms, including tablets, chewable tablets, capsules, liquid, extended-release (long-acting) tablets, and orally disintegrating tablets. All of these forms are taken orally, and you don’t need to eat food beforehand.

Acetaminophen can also come in the form of a suppository (a solid dosage form inserted into your rectum, vagina, or urethra, where it dissolves).

You should take acetaminophen exactly in accordance with your prescription directions or with the dosage directions on the bottle, if you purchased it over-the-counter. Be sure to not take more than one product that contains acetaminophen at a time. If you are on other medications, check the ingredient label, or talk to your doctor if you’re unsure. Besides APAP and paracetamol, acetaminophen may appear on labels under abbreviations such as AC, Acetaminoph, Acetaminop, Acetamin, or Acetam. Do not take acetaminophen if you drink three or more alcoholic drinks every day, even if the medication is not ingested immediately before or after drinking. Be sure to tell your doctor if you’ve ever had liver disease, as acetaminophen can affect the liver.

Along with effects on the liver, acetaminophen can also cause blisters, rashes, hives, itching, swelling, hoarseness, and difficulty breathing or swallowing. Symptoms of overdose include nausea, vomiting, loss of appetite, sweating, extreme tiredness, unusual bleeding or bruising, pain in the upper right part of the stomach, and jaundice (yellowing skin or eyes). If you have any of these symptoms, you should seek immediate emergency medical attention (18).

When it comes to pain relief, you have many different options to choose from, including NSAIDs and acetaminophen.

Acetaminophen is not an NSAID, meaning that it cannot reduce inflammation, but as an antipyretic analgesic, it will reduce fever and relieve mild pain. APAP, another name for acetaminophen, is best suited for treating headaches, body aches, fever, and arthritis. When it comes to acute musculoskeletal pain or chronic body issues, NSAIDs outperform acetaminophen. However, acetaminophen carries fewer side effects: These effects tend to be more liver-related and less heart or stomach-related. Tylenol will not irritate your stomach in the same way Aleve or Advil can.

If you are taking multiple medications, be sure to look at all the ingredients to avoid overdosing on acetaminophen. Remember do not take more than 3,000 mg per day, and do not take the maximum dose for more than two consecutive days.

Despite some of its risks and its mild potency, acetaminophen can still be a good choice for a pain reliever. Acetaminophen has been proven to relieve pain, and its efficacy can vary from person to person (in a positive or negative way). The key as you consider acetaminophen for your pain is to keep the key points we’ve discussed in this article in mind.