NSAID Toxicity

Two articles currently being prepared for publication in The Medical Letter touch on the risks associated with NSAIDs.

One is a brief article reporting that the FDA has approved 2 generic formulations of celecoxib (Celebrex), which is the only COX-2 selective NSAID remaining on the market in the US. The COX-2 selective drugs, also called coxibs, were supposed to provide the analgesic and anti-inflammatory effects of nonselective NSAIDs without their GI toxicity. They did that, but their prothrombotic effects took down first rofecoxib (Vioxx) and then valdecoxib (Bextra). Celecoxib was the least COX-2 selective of the coxibs, and it has not only survived but prospered, ranking among the 25 drugs most prescribed in the US. There is general agreement that celecoxib causes less GI toxicity than ibuprofen or naproxen. Whether it could be a little less heart-healthy than the nonselective NSAIDs is unclear; in any case, the absolute risk is small.

The second article is on Drugs for Osteoarthritis, which many seniors self-medicate effectively with NSAIDs. But we should probably warn them against doing that because even if they take celecoxib and minimize the risk of GI bleeding, they are still susceptible to the renal toxicity of NSAIDs, which is unaffected by COX selectivity and is much worse in the elderly. Renal side effects of NSAIDs include salt and water retention, decreased effectiveness of antihypertensive meds, decreased effectiveness of diuretics, decreased urate excretion, and hyperkalemia. So they develop hypertension or their pre-existing hypertension grows worse, they go into heart failure, they develop gout, and their kidneys fail. Acetaminophen may be a little less effective, but as long as they don’t overdose, it’s probably a lot safer.

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  1. Rick Cohn says:

    BP and GFR easily can and should be monitored; if stable, the benefits of taking NSAIDs far outweigh the risks to the kidney.

  2. Ken Grauer, MD says:

    @ Rick – I bet many of the many patients admitted each year for NSAID-related GI bleeding no longer agree that the “benefits of NSAIDs far outweigh the risks”. Like everything – it is a balance with potential for benefit from a medication and potential for harm. The patients tending to need longterm NSAIDs the most are the very ones at greatest risk for adverse renal, GI and cardiovascular effects. Most of them had never given reasonable dose acetaminophen a chance – which doesn’t make sense given its much safer overall risk profile.

    • Rick Cohn says:

      Ken, you are absolutely correct with respect to GI side effects, especially for patients who take an NSAID on a daily basis. My comment was related more to the relatively low risk of adverse effects on BP and GFR with occasional use of NSAIDs for arthritis type pain, the type of pain that responds less well to acetaminophen.

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