Making sense of OTC pain relievers: A decision guide

Millions of us experience occasional aches and pains and reach for an over-the-counter (OTC) pain reliever. But between acetaminophen, ibuprofen, aspirin and so many more, how do you know which type is right for you? Here is some information to help you safely use OTC pain relievers.

(available as generic, also sold as Tylenol)

Acetaminophen is widely used for pain relief and reducing fever. Acetaminophen may help relieve pain by blocking pain signals within the central nervous system (brain and spinal cord). Acetaminophen comes in many forms, such as tablets and capsules for adults or liquid and rectal suppositories. Acetaminophen is also commonly found in combination with other pain relievers, cough suppressants, and other cough and cold medications. Acetaminophen does not reduce inflammation, unlike aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) below. However, unlike NSAIDs, acetaminophen will not irritate the stomach or intestinal lining.

It is important not to exceed the recommended dose unless directed by a doctor. Taking too much acetaminophen can damage the liver and even cause death. You might accidentally take too much acetaminophen if you do not follow directions on the prescription or package label carefully, or if you take more than one product containing acetaminophen. (More than 600 products contain acetaminophen, so be sure to read labels.)

Cases of severe liver injury have been reported when people took more than one acetaminophen-containing product at the same time, drank alcohol when taking acetaminophen, or took more than the recommended dose of an acetaminophen-containing product in a 24-hour period. People who drink more than three alcoholic drinks a day are at a greater risk of liver damage when taking acetaminophen. If you have a history of stomach bleeding or suffer from liver or kidney disease, talk to your doctor before taking either acetaminophen or NSAIDs.

(Available as generic, also sold as Motrin, Motrin IB or Advil)

Ibuprofen is commonly used to reduce fever and to relieve minor aches and pain from headaches, muscle aches, arthritis, menstrual periods, the common cold, toothaches and backaches.

Ibuprofen is in a class of medications called nonsteroidal anti-inflammatory drugs (NSAIDs) that work by stopping the body's production of a substance that causes pain, fever and inflammation.

All NSAIDs may cause stomach bleeding and stomach ulcers, or holes in the stomach or intestine. These problems may develop at any time during treatment. This risk of stomach bleeding and ulcers increases in people who are over 60, are taking prescription blood thinners, are taking steroids, smoke tobacco, receiving chemotherapy, have a history of stomach bleeding or ulcers, gastrointestinal disease, and/or have other bleeding problems.

The use of NSAIDs can cause kidney damage. This risk may increase in people who are over 60 years of age, are taking a diuretic (a drug that increases the excretion of urine), have high blood pressure, heart disease, or kidney disease.

All NSAIDs, except aspirin, may increase the risk of heart attack, heart failure and stroke. Ibuprofen may also cause a severe allergic reaction, especially in people allergic to aspirin.

There are more than 900 OTC and prescription medicines that contain an NSAID, and taking more than one product at a time can increase your risk of side effects.

(Available as generic, also sold as Aleve)

Naproxen is in the class of medications called NSAIDs. Naproxen has essentially the same warnings as ibuprofen. Some studies suggest that naproxen may be safer on the heart than other NSAIDs, but the data are not conclusive. The risk of heart problems is highest among people with known heart disease or multiple risk factors for heart disease.

An advantage to naproxen is that it is longer acting than ibuprofen. Both naproxen and ibuprofen are considered more effective for reducing inflammation than aspirin.

All NSAIDs may cause stomach bleeding and stomach ulcers, or holes in the stomach or intestine. These problems may develop at any time during treatment. This risk of stomach bleeding and ulcers increases in people who are over 60 years of age, are taking prescription blood thinners, are taking steroids, have a history of stomach bleeding or ulcers, and/or have other bleeding problems.

There are more than 900 OTC and prescription medicines that contain an NSAID, and taking more than one product at a time can increase your risk of side effects.

A common medication, aspirin has been used for many years to relieve mild to moderate pain. It is considered an NSAID. Aspirin can also cause gastrointestinal side effects. For children and adolescents, aspirin is not recommended to treat flu-like symptoms or viral illnesses due to the risk of Reye's syndrome, a very rare disorder that can cause serious liver and brain damage.

One of aspirin's properties is its ability to thin the blood. Studies show that aspirin can help to lower the chances of a heart attack or a stroke caused by a blood clot in the brain. However, studies show that this benefit is among people who had a previous heart attack or stroke or have disease of the blood vessels in the heart. The benefits of daily low-dose aspirin therapy to prevent recurrent cardiovascular disease (CVD) events are well-established. Aspirin's use for primary prevention of CVD, however, has been the subject of controversy because of questionable benefits and increased bleeding risk. Aspirin can also interact with other medications and supplements you take. You should always talk with your healthcare provider before using aspirin for heart disease.

(Available as generic, also sold as Voltaren Pain Gel, Motrin Arthritis Pain, Aspercreme Arthritis Pain )

Diclofenac topical is an OTC topical NSAID gel or cream. The topical contains the NSAID diclofenac sodium. It is applied to the skin for the temporary relief of pain from osteoarthritis pain and musculoskeletal pain. Diclofenac topical OTC is the same strength  available by prescription. Since it is an NSAID, it carries similar safety warnings as other NSAIDs. These include the risk of a severe allergic reaction, especially in people allergic to aspirin, stomach bleeding warning and a heart attack and stroke warning. Also, prescription-strength diclofenac has been linked to liver damage. However, since diclofenac topical is absorbed through the skin and not through the stomach like other NSAIDs, it may pose less danger.

Drug interactions involving OTC pain relievers can occur. For example, aspirin can interact with prescription medications that thin the blood, such as warfarin or dabigatran and steroids, increasing the risk of stomach bleeding. There are thousands of possible drug interactions but you can avoid them by:

• Making sure you know which medicines, vitamins, foods and herbal products can interact with the drugs you're taking.
• Asking your doctor and pharmacist questions.
• Always getting and following instructions on how to take your medicines and what to avoid while taking them. There are trusted web resources for learning more about your medicines.
• Reading the label. All OTC medicines must have all of their active ingredients listed on the package.
• Giving your doctor and pharmacist a complete list of your medicines, including over-the-counter and herbal products. This allows them to check for any potential drug interactions.
• Sticking with one pharmacy, if possible. This way, your pharmacist can check for drug interactions when filling your prescription.

Like all medicines, OTC pain relievers can cause side effects in some people. People in certain age groups or with certain health conditions may be more at risk for experiencing side effects or interactions. Ask your pharmacist or healthcare provider about possible OTC pain reliever options for your condition.

Andy Stergachis, PhD, BPharm, is the director of the Global Medicines Program at the University of Washington in Seattle and a subject expert on public health and pharmacy-related topics.

Clinically reviewed and updated June 2023.