NSAIDs: Where Do We Go From Here?

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NSAIDs: What The FDA Is Advising

Along with its recent recommendations on Bextra and Celebrex, the Food and Drug Administration (FDA) is requesting labeling changes to all non-selective NSAIDs. The labeling changes emphasize an increased awareness of potential cardiovascular and gastrointestinal risks of these medications, and “stronger reminders” about adhering to instructions regarding the dose and duration of treatment.

Specifically, when it comes to prescription products that contain non-selective NSAIDs, the FDA has asked manufacturers of these products to revise their labeling as follows. The labeling will include:
• a medication guide and a boxed warning regarding potential serious adverse cardiovascular and gastrointestinal events; and
• a contraindication for use in patients who have recently undergone coronary artery surgery.

The FDA says the available data does not suggest an increased risk of serious cardiovascular events for short-term use of non-selective NSAIDs that are available over the counter (OTC). However, the agency has requested labeling changes that will include:
• more specific information about potential cardiovascular and gastrointestinal risks;
• instructions about which patients should consult a doctor before using these medications;
• a warning about potential skin reactions; and
• stronger reminders about limiting the dose and duration of treatment in accordance with packaging instructions or a physician’s advice.

Since aspirin, ibuprofen, indomethacin, piroxicam and phenylbutazone are metabolized by multiple pathways, dosage adjustments are usually unnecesssary in patients with hepatic disease or in elderly patients with normal renal function.
NSAIDs: Where Do We Go From Here?
It has generally been accepted that the major therapeutic effect of aspirin and the NSAIDs results from the inhibition of prostaglandin synthesis.
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Author(s): 
By Anthony R. Iorio, DPM, MPH

   Nonsteroidal antiinflammatory drugs (NSAIDs) are among the most widely used medications today. Considering their well-documented efficacy in managing fever, mild to moderate pain and, at higher doses, inflammation, such widespread use is generally appropriate. In 1997, over 74 million NSAID prescriptions were dispensed in the United States, representing approximately 4.5 percent of all prescriptions. In addition, nonprescription NSAIDs such as aspirin and ibuprofen contribute significantly to the use of this class of medications. It is estimated that 1 to 2 percent of the North American population use NSAIDs on a daily basis.

   NSAIDs have proven efficacy in a variety of disorders associated with pain and inflammation. Although Food and Drug Administration (FDA)-approved labeling differs to varying degrees for NSAIDs marketed in the United States, this does not always reflect actual differences in efficacy among these agents. (See “NSAIDs: What The FDA Is Advising” below.) By and large, selecting a NSAID for most conditions is largely empiric with exceptions in a few instances.

   For years, NSAIDs have been a mainstay in the treatment of various arthropathies including rheumatoid arthritis, osteoarthritis and ankylosing spondylitis. In regard to the NSAIDs approved for treating rheumatoid arthritis and osteoarthritis, all are considered to have comparable efficacy. As a result, considerations for selecting one agent over another are frequently based on the perceived incidence of gastric side effects, cost and frequency of administration. Recent reports have also raised concern that some NSAIDs may adversely affect chondrocyte function in patients with osteoarthritis. This potentially could accelerate joint deformity in these patients.

   Although this is yet to be confirmed, when it comes to osteoarthritis without a significant inflammatory component, one can frequently treat this with simple analgesics such as acetaminophen. When treating ankylosing spondylitis, indomethacin is considered the drug of choice based on its greater than 90 percent efficacy. However, clinicians have used other NSAIDs with good success in treating this condition.

   NSAIDs frequently are indicated for the treatment of mild to moderate pain associated with a variety of conditions, including post-extraction dental pain, episiotomy pain and pain due to soft tissue injuries. In many cases, their efficacy is comparable to many commonly used oral codeine-containing medications. NSAIDs also are used widely for the treatment of pain and inflammation associated with musculoskeletal disorders and for muscle contraction headaches. However, indomethacin is not recommended in the latter condition because of its ability to constrict cerebral vessels.

   One can effectively use NSAID therapy to treat primary dysmenorrhea, which is characterized by prostaglandin-mediated uterine contractions. Aspirin in doses of 500 mg and 600 mg is less effective than other NSAIDs in treating this condition. Also keep in mind that response rates to diclofenac may be lower than other NSAIDs due to its short half-life and sequestering in synovial fluid.

   Phenylbutazone and indomethacin have been the most widely used NSAIDs for treating gout but other NSAIDs also have demonstrated efficacy. Based on their more favorable adverse effect profiles, indomethacin and other NSAIDs are preferred over phenylbutazone. For acute attacks of gout, one would usually administer a large NSAID loading dose initially and subsequently follow the usual recommended doses.

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