Guidelines to Help Reduce the Side Effects of NSAIDs (Nonsteroidal Anti-inflammatory Drugs)

• What are NSAIDs?
• What are possible side effects of NSAIDs?
• How should you think about taking NSAIDs in view of the possible side effects?
• What about using NSAIDs during pregnancy?
• What is the proper dosing for NSAIDs?
• Can I combine NSAIDs with other drugs?
• When should I stop the drug and get immediate medical attention?
• When should I call my doctor about changing NSAID dosage or medications?

What are NSAIDs?

Nonsteroidal anti-inflammatory drugs are a group of drugs that are prescribed to reduce the pain and inflammation of arthritis. Some of these drugs require a prescription, while others are available without one (over-the-counter or OTC). They include such drugs such as asprin, ibuprofen and naproxen. Here is an extensive list of various NSAIDs:

NSAIDs do not include drugs that are purely pain relievers, such as acetaminophen (Tylenol) or codeine. A more recent group of NSAIDs known as COX-2 selective or COX-2 specific inhibitors are covered in a separate article on COX-2 inhibitors – presently limited to the agent celecoxib (Celebrex.)

NSAIDs are generally tolerated very well by many patients, which is fortunate because these drugs are often very helpful for people with pain and inflammation. Most side effects are minor and easily reversible by discontinuing the drug or by adding a drug to counter such effects. The risk of serious side effects is small, but there are some serious considerations with these medications, as discussed below. Being aware of the possible side effects of these drugs can make them even safer to use. Although most side effects are minor, there is still a genuine concern regarding gastrointestinal problems (such as ulcer development) and cardiovascular side effects.

If any of these guidelines are not clear, or if you think it does not apply to you, be sure to discuss the issue with your physician.

What are possible side effects of NSAIDs?

The most common side effects of NSAIDs are gastrointestinal problems, including stomach irritation and reflux. More rarely, NSAIDs can contribute to heart problems and increase the risk of cardiovascular conditions.

Gastrointestinal symptoms

• Gastrointestinal symptoms are the most common side effects of NSAIDs. They are most likely to be stomach irritation and the sensations known as "heart burn" (which has nothing to do with your heart). In severe cases, NSAIDs can irritate the lining of your stomach so that an ulcer (a small erosion) forms. In the worst cases, such an erosion can lead to internal bleeding, which may be life-threatening. Perforation, meaning a “hole” in the stomach, can also occur in rare cases. This is an urgent problem requiring prompt medical attention.
• Stop the drug and call your physician immediately if you have any severe abdominal pain or a black, tarry stool (bowel movement) or any blood in your stool.
• To help reduce irritation of the stomach and prevent an ulcer,
  • Take NSAIDs at the end of a full meal or with an antacid
  • Limit alcohol intake (since alcohol can also irritate your stomach)
• If you develop gastrointestinal problems, your physician may switch you to another drug (such as a COX-2 selective inhibitor – see the below section on this type of agent) or may add a drug to help reduce stomach irritation.
• Drugs that reduce stomach irritation include misoprostol (Cytotec), or a proton pump inhibitor such as omeprazole (Prilosec), esomeprazole (Nexium), pantoprazole (Protonix), lansoprazole (Prevacid), or rabeprazole (Aciphex). These drugs can considerably reduce your risk of an ulcer and internal bleeding.

The black box warning for NSAIDs related to gastrointestinal risk reads as follows, in an example from the labeling for the NSAID naproxen (Naprosyn®):

NSAIDs cause an increased risk of serious gastrointestinal (GI) adverse events, including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events.

Heart problems

The FDA has required a block box warning about cardiovascular thrombotic events be placed in the package description of all NSAIDs other than aspirin, including COX-2 specific and selective agent, and patients at high risk for cardiovascular disease need to weigh the risks and benefits with their physician before taking any NSAID or (COX-2 specific or selective agent). The black box warning for NSAIDs related to cardiovascular risk reads as follows, in an example from the labeling for the NSAID naproxen (Naprosyn®):

"Cardiovascular risk: Serious cardiovascular thrombotic events: Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction (MI) and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use."

How should you think about taking NSAIDs in view of the possible side effects?

Years ago, doctors thought of NSAIDs as being very safe. They still are acceptably safe for many people, but longer-term experience and medical studies have shown that there are definite risks. Think about these things before you start NSAIDs and consider them again if you are taking them for a while:

• Do you have risk factors for the side-effects of these medications? For example, do you have a prior history of ulcer, a known bleeding problem? Are you are higher-than-average cardiac risk, such as if you have had a heart attack, have high blood pressure (especially if not well-controlled) or have diabetes. Older people have more GI and cardiovascular risk from NSAIDs.
• Have you been told of abnormal kidney function? NSAIDs can negatively affect kidney function.
• Will you be taking NSAIDs for a short or long time? Although heart issues have been described after short uses of NSAIDs, most of the time the problems come with prolonged use. There are situations where long-term use of NSAIDs is appropriate, but in many other situations the need for long-term NSAIDs calls for a discussion with your health care provider about possible alternatives.

What about using NSAIDs during pregnancy?

A good resource for the use of NSAIDs in pregnancy can be found at MotherToBaby's factsheet on naproxen. They point out that “It is unclear if naproxen use may affect the ability to become pregnant.” They note that “studies have suggested that the use of NSAIDs may increase the chance of miscarriage,” but suggest that this may be in the setting of long-term use of NSAIDs. Data to date overall do not suggest that NSAIDs cause any abnormalities of babies. NSAIDs are not recommended for use after week 20 of a pregnancy.

What is the proper dosing for NSAIDs?

When you are trying an NSAID for the first time, take the full dose prescribed every day, unless instructed otherwise. It may take as long as two weeks to build up to a "blood level" of the drug, and the drug may not help very much until then. If you take the drug irregularly, you may never know whether it actually can help you. This could lead to your being switched to a second drug when the first one actually could have helped. Each new drug you take carries a risk of allergic reaction (such as skin rash). Therefore, it's important to find out if a drug can help you before switching to another.

Do not exceed the dose of the drug prescribed. The extra benefit is usually small and the increased risk is significant.

If you are taking the medicine regularly and miss a dose, take it as soon as possible. However, if it is almost time for your next dose, skip the one you missed and go back to your regular schedule. Do not take a double dose. If your arthritis improves, discuss with your physician the possibility of decreasing your dose of the NSAID.

Can I combine NSAIDs with other drugs?

Do not mix one NSAID with another. For example, don't take aspirin or ibuprofen with any other nonsteroidal anti-inflammatory drugs. However, your physician may wish you to combine low-dose aspirin with an NSAID for heart attack or stroke prevention. This is an individual decision for each patient, and you should discuss this with your physician, since combining an NSAID with aspirin can increase the risk of ulcer. Acetaminophen, especially in low dose, appears less likely to irritate the stomach than NSAIDs, so in many cases it is reasonable to take acetaminophen along with (or instead of) NSAIDs.

Always read the ingredients listed on the label of over-the-counter products. If acetylsalicylic acid or salicylate is listed, it may be better not to take this with NSAIDs, unless advised by your physician. Keep in mind that Alka-Seltzer, Anacin and some types of Excedrin contain aspirin.

If you are taking medications for high blood pressure, have your pressure checked regularly while on the nonsteroidal anti-inflammatory drug. This is especially important within the first several weeks of starting the drug. In some patients, NSAIDs can elevate the blood pressure.

When should I stop the drug and get immediate medical attention?

You should cease taking NSAIDs if:

• Signs of allergy occur, such as rapid breathing, gasping, wheezing, hives, skin rashes, puffy eyelids, and/or rapid heart beat.
• You develop:
  • vision abnormalities.
  • dizziness, depression or confusion.
  • yellowing of the eyes that could indicate liver injury (although liver injury is rare and your liver function is checked when you have standard chemistry blood tests, which should be done periodically, when you are taking an NSAID).
• Your urine becomes cloudy or bloody, the amount of urine you pass should suddenly decrease, or you develop new ankle swelling, all of which could indicate kidney problems. This is especially important to watch for if your kidney function has been noted, on lab testing, to have been abnormal in the past.

When should I call my doctor about changing NSAID dosage or medications?

Talk to your doctor about switching away from NSAIDs if:

• You develop swelling of the ankles or sudden weight gain after starting one of these drugs due to fluid retention.
• You develop decreased hearing or ringing in your ears.
• You are pregnant or planning to become pregnant.

Updated: 12/10/2021

Authors

Theodore R. Fields, MD, FACP
Attending Physician, Hospital for Special Surgery
Professor of Clinical Medicine, Weill Cornell Medical College

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