COX-2 inhibitors: what you need to know.

Pain has been in the headlines lately, ever since two of the most common prescription pain relievers, rofecoxib (Vioxx) and valdecoxib (Bextra), were pulled from the market when studies found they could increase the risk of heart attack.

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The enhanced scrutiny of these drugs, which belonged to the COX-2 class of pain-killers, also sparked closer investigation of other non-steroidal anti-inflammatory painkillers (NSAIDs), including common over-the-counter (OTC) medications such as naproxen (Aleve) and ibuprofen (Motrin). The result? Significantly stronger warnings now are on most OTC and prescription non-narcotic painkillers, including aspirin. (18)

Almost overnight, it seemed, millions of Americans found themselves either without the medications they'd come to rely on for pain relief or with numerous questions and concerns about the medications they continued to take. In fact, a National Women's Health Resource Center online survey found 66 percent of respondents were at least somewhat confused about which OTC pain reliever to take.

But what seems to have been missed in all the doom-and-gloom headlines, according to Steven Chen, PharmD, an assistant professor of clinical pharmacy at the University of Southern California School of Pharmacy in Los Angeles, is the fact that all drugs have potential risks, requiring careful monitoring. In today's regulatory climate, for example, some experts doubt that even aspirin with its risk for severe stomach bleeding would be approved as a new drug. (19)

Plus, experts note, there are still dozens of other NSAIDs on the market. "No one NSAID has ever been proven to be consistently better than any other," says John Meyerhoff, MD, a rheumatologist and assistant professor of medicine at Johns Hopkins University School of Medicine in Baltimore. In fact, despite the hype about the ability of the COX-2s to save your stomach, only one--rofecoxib (Vioxx)--had any evidence suggesting that it caused fewer stomach ulcers than other NSAIDs.

The key, notes Dr. Chen, is to take the right type of pain reliever for your condition. He always recommends starting with acetaminophen (Tylenol and generic brands), shown to be effective in managing osteoarthritis pain without the gastrointestinal bleeding risks of NSAIDs. One caveat: Avoid acetaminophen if you have any liver damage or are a heavy drinker (three or more drinks a day).

Acetaminophen has one other drawback: it doesn't help with the pain associated with inflammation. For that, Dr. Chen recommends non-acetylated salicylates such as salsalate (Disalcid) or diflunisal (Dolobid) before jumping to prescription NSAIDs. "Prescribers forget this class of drugs because of all the heavy advertising for the NSAIDs," he says, "but they're much safer than traditional NSAIDs." They don't harm the stomach's protective lining, and they appear less likely to contribute to kidney problems, as traditional NSAIDS or long-term use of acetaminophen can. Their only drawback? There are no OTC forms.

Additionally, pain medication that's applied directly to the pain site, including lidocaine patches and capsaicin ointment, may also help with arthritis pain, as can several antidepressants, particularly if you also have pinched nerves. Plus, Dr. Meyerhoff notes, the nutritional supplements glucosamine and/or chondroitin could reduce joint pain, although they won't restore the joint.

Then there are lifestyle approaches. Losing weight can reduce the pain of osteoarthritis by relieving pressure on the joints, and strengthening your thigh muscles can help relieve pain from osteoarthritis of the knee.

Don't write off the entire COX-2 inhibitor class of drugs, says Dr. Chen. Although the FDA has decided that all NSAIDs are associated with gastrointestinal and cardiovascular risk, the risk appears to be linked to how much the drug affects, or selects, the COX-2 enzyme versus the COX-1 enzyme. "Based on this, Vioxx and Bextra may be associated with a higher risk of a heart attack because they are more potent inhibitors of COX-2 enzymes than Celebrex."

So, don't be afraid of taking over-the-counter NSAIDs or even acetaminophen for pain, Dr. Chen offers. "They have been around for a long time and, when taken at OTC doses, they appear to be safe."