Guidelines to Help Reduce the Side-Effects of NSAIDs (Non-Steroidal Anti-Inflammatory Agents)

How to Reduce Drug Side Effects


Theodore R. Fields, MD, FACP

Attending Physician, Hospital for Special Surgery
Professor of Clinical Medicine, Weill Cornell Medical College

Non-steroidal anti-inflammatory drugs (NSAIDs) 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 (generic names first, brand names in parentheses):

aspirin
diclofenac (Voltaren)
etodolac (Lodine)
fenoprofen (Nalfon)
flurbiprofen (Ansaid)
ibuprofen (Motrin, Advil, Rufen)
meclofenamate (Meclomen)
naproxen (Aleve, Naprosyn)
indomethacin (Indocin)
ketoprofen (Orudis, Oruvail)
oxaprozin (Daypro)
piroxicam (Feldene)
salsalate (Disalcid, Trilisate)
sulindac (Clinoril)
tolmetin (Tolectin)

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. 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 re: gastrointestinal problems, such as ulcer development, and cardiovascular side-effects, as discussed.

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

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.
  • 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 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 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). Only lansoprazole, at this time, has received an official FDA indication for protection of ulcer in patients on non-steroidal anti-inflammatory agents. These drugs can considerably reduce your risk of an ulcer and internal bleeding.

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

"Gastrointestinal Risk:  NSAIDs cause an increased risk of serious gastrointestinal 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 are at greater risk for serious gastrointestinal 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 NSAID’s related to cardiovascular risk reads as follows, in an example from the labeling for the NSAID naproxen (Naprosyn®):

"Cardiovascular Risk:  NSAIDs may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk."

Dosing

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 2 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.

Combining NSAIDs with Other Drugs

  • Do not mix one NSAID with another. For example, don't take aspirin or ibuprofen with any other non-steroidal anti-inflammatory agents. However, your physician may wish you to combine low-dose aspirin with an NSAID for heart 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 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, some types of Excedrin, and even Pepto-Bismol contain aspirin.
  • If you are taking medications for high blood pressure, have your pressure checked regularly while on the non-steroidal anti-inflammatory agent. This is especially important within the first several weeks of starting the drug. In some patients, NSAIDs can elevate the blood pressure.

When to Stop the Drug and Get Immediate Medical Attention

  • If signs of allergy occur, such as rapid breathing, gasping, wheezing, hives, skin rashes, puffy eyelids, and/or rapid heart beat occur.
  • If you develop vision abnormalities.
  • If you develop dizziness, depression, or confusion.
  • If you develop 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).
  • If 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 to Call Your Doctor About Changing Dosage or Medications

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

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