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What to D.O.

What to D.O.

When Ibuprofen Fails, Naproxen Isn't the Answer

Pescatore, Richard DO

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doi: 10.1097/01.EEM.0000532169.46079.0a

    Seeking adequate and appropriate analgesia is a constant task for emergency physicians. Whether for acute musculoskeletal pain, diagnosis-eluding bellyaches, or longstanding allodynia, we often find ourselves at a therapeutic crossroads. Where forward-thinking initiatives like St. Joseph's ALTO program ( and Dr. Sergey Motov's exceptional work ( offer nonopioid alternatives in the ED, our options seem comparatively limited at discharge.

    It's a fairly familiar routine—the patient, having tried acetaminophen and ibuprofen at home, declares their inefficacy. Adjunctive therapies have their place, but we often return to a common conundrum, debating the provision of opioid analgesia versus substituting naproxen for the apparently unhelpful ibuprofen. Unfortunately, it's likely that this switch, while well intentioned, is little more than clinical subterfuge. As we continue to strive to limit opioid prescriptions, a deeper exploration and understanding of NSAIDs may offer more useful and genuine alternatives.

    NSAID sub-classification, taught to us all in the didactic drudgery of medical school, seems to receive little acknowledgement in the clinical world. A patient's lack of response to ibuprofen likely heralds a similarly limited effect of naproxen, also a propionic acid. Different patients can respond to different NSAID subclasses in a variety of ways, however.

    This variability is likely multifactorial, influenced in part by genetic differences in the CYP450 system, plasma half-lives and protein binding, and any number of pharmacologic- or patient-specific idiosyncrasies. NSAIDs with longer half-lives, for example, enable drug concentrations to equilibrate between plasma and synovial fluid, increasing accumulation at sites of inflammation. (Arthritis Res Ther 2013;15[Suppl 3]:S2.)

    Classes and Dosing of NSAIDs

    Patient Responses

    All NSAID subclasses act via COX inhibition and interference with prostaglandin synthesis, but the individual groups demonstrate a plethora of properties not dependent on arachidonic acid metabolism. These differences form the physiologic basis for improved patient response to different subclasses. Where propionic acids may more effectively inhibit superoxide generation and neutrophil aggregation, acetic acid derivatives likely have different effects on signal transduction pathways and inflammatory cytokine concentration in synovial fluid. (Osteoarthritis Cartilage 2013;21[9]:1400.)

    Clinical and laboratory data investigating differences in patient response to NSAID subclasses have been mixed. One systematic review of nearly 1,000 rheumatologic patients demonstrated clear superiority of propionic over acetic acids (Clin Exp Rheumatol 2013;31[5]:731), where a blinded trial in patients with ankle sprains showed the opposite. (J Int Med Res 1991;19[2]:121.) One study showed profound differences between osteoarthritis progression in patients using oxicams versus ibuprofen or diclofenac. (Arthritis Rheum 2005;52[10]:3137.)

    Evidence-based-medicine purists might cite these inconsistent signals as evidence of interchangeability, but it's more likely that there is significant variability in clinical response among individual patients and that no differences in NSAID subclass efficacy will ever be demonstrated among populations. (Arthritis Rheum 1994;37[3]:316.)

    The opioid epidemic has been and will likely remain the greatest public health threat of our time, and as clinicians on the front line of American health care, emergency physicians must seek viable and genuine alternatives for pain management. There is little justification for using naproxen and ibuprofen interchangeably when one of the two has failed.

    Consider, instead, utilizing diclofenac, meloxicam, or another therapeutic cousin. Transitioning patients in need from a reportedly ineffective propionic acid to an alternative NSAID subclass is a reasonable approach with firm physiologic grounding, and may make a big difference where other efforts have failed.

    Wolters Kluwer Health, Inc. All rights reserved.