Coxibs versus Combination NSAID and PPI Therapy for Chronic Pain: An Exploration of the Risks, Benefits, and Costs

Harvard University, Cambridge, Massachusetts, United States
Annals of Pharmacotherapy (Impact Factor: 2.06). 07/2006; 40(6):1052-63. DOI: 10.1345/aph.1G493
Source: PubMed


To systematically review studies qualitatively to compare the risks (gastrointestinal [GI] and cardiovascular) and benefits (pain control) of cyclooxygenase-2 inhibitors (coxibs) relative to an alternative therapy of a nonselective nonsteroidal antiinflammatory drug (NSAID) combined with a proton-pump inhibitor (PPI) and explore circumstances when coxibs may be appropriate.
Relevant studies were identified through a search of MEDLINE (Ovid Technologies, 1985-November 2005; English language, clinical trial), PubMed (1985-November 2005; English language, clinical trial, humans), and the Cochrane Collaboration using the terms selective COX-2 inhibitors and coxibs, as well as the various chemical names for specific coxib agents. Studies that compared a coxib with a nonselective NSAID and provided data concerning our outcomes of interest were included and categorized by the outcome variable, as well as by the specific coxib studied.
The majority of the numerous studies that evaluated pain as an endpoint showed no difference between coxib and nonselective NSAID therapy. However, while limited, preliminary safety data regarding the effects of both classes on the upper and lower GI tract suggest coxib superiority. Although coxibs are associated with an increased risk of cardiovascular adverse events (CVEs) compared with placebo, this effect has not been conclusively shown compared with nonselective NSAIDs. Currently, coxib therapy is more expensive than combination therapy using a nonselective NSAID plus a PPI.
Compared with combination therapy including a nonselective NSAID and PPI, coxibs provide equivalent pain control and may have a lower GI tract complication profile, but at an unknown increased risk of CVEs and a greater financial cost. Coxib therapy may be an appropriate treatment for chronic pain in select patients with higher risks of GI complications, lower risk of CVEs, and in whom greater cost is not a restraint.

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    • "However, the expression of COX-2 is induced as a response of inflammation whereas COX-3 was observed to be abundant in the cerebral cortex [2] [3]. All NSAIDs have a similar effect on reducing pain [5] [6]. These include the selective NSAID or COX-2 inhibitor, Celecoxib, nonselective NSAIDs, such as ibuprofen and aspirin, and partially selective NSAIDs, such as meloxicam, nabumetone, and etodolac. "
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    ABSTRACT: We have developed a series of aminoacetylenic isoindoline-1,3-dione compounds and showed their anti-inflammatory activities by reducing carrageenan-induced rat paw edema and modulating proinflammatory and anti-inflammatory cytokines. In the present study and due to efficacy reasons, we are exploring only two of these compounds, namely, ZM4 and ZM5, to reveal their analgesic activity and toxicity. Following oral administration, both compounds were effective in reducing significantly ( P < 0.05 –0.001) acetic acid-induced writhing behavior, hot plate latency test, and formalin-induced paw licking time as antinociceptive indicators in mice and rats, respectively. Regarding the toxicity, the acute (20, 50, and 150 mg/kg) and repeated oral administration (10, 20, and 50 mg/kg) of these compounds for ten days did not produce any mortality and the compounds were considered well tolerated. However, repeated oral administration of 50 mg/kg of both compounds induced erythropoiesis by means of increasing significantly red blood cells, hemoglobin, and packed cell volume. Moreover, these compounds did not induce gastric lesions in the stomach of experimental animals at the doses that exhibited analgesic and anti-inflammatory activity compared to indomethacin as a positive control. The results indicate that ZM4 and ZM5 possess potential analgesic activity while being preliminarily safe and have minimal ulcerogenic activity.
    12/2012; 2012(11):657472. DOI:10.5402/2012/657472
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    • "Concomitant administration of misoprostol, H2-receptor antagonists, or proton pump inhibitors may reduce the risk for gastrointestinal ulceration in chronic NSAID users and should be prescribed if gastrointestinal risk is high (Hawkey et al. 2007; Rostom et al. 2002). Whether an NSAID prescribed along with a proton pump inhibitor provides superior protection from incident dyspepsia, bleeding, or other gastrointestinal tract complications remains unclear (Hur et al. 2006; Spiegel et al. 2006). NSAIDs may adversely affect blood pressure control (Aw et al. 2005; Izhar et al. 2004; Whelton et al. 2001), renal function (Juhlin et al. 2005; Niccoli et al. 2002), and heart-failure management (Juhlin et al. 2004). "
    Handbook of Headache, 01/2011: chapter Managing Headache in Older People;
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    • "The benefit from the analgesics, reduction of pain, must be evaluated against the risk for side effects in each individual patient.20 Cost is also becoming increasingly important, and in many countries, cheapest generic product is recommended in order to reduce direct drug costs. Cost considerations should, however, take into account not only the direct prescribed drug cost but also costs associated with coprescriptions in order to prevent or treat side effects and other resources needed, ie, any additional contacts with health care.21 We found a clear switch, increase in prescription of nonselective NSAIDs and a reduction in prescription of Coxibs. "
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    ABSTRACT: To study the prescription of oral analgesics for musculoskeletal pain by primary care physicians over a 5-year period in Sweden. A retrospective automatic database review of patient records at four primary health care centers. All prescriptions of NSAIDs, weak opioids, and coprescriptions of gastroprotecting medications to patients with musculoskeletal were retrieved for the period January 1, 2004 to November 11, 2008. A total of 27,067 prescriptions prescribed to 23,457 patients with musculoskeletal pain were analyzed. Of all prescriptions, NSAIDs were the most commonly prescribed analgesic comprising 79%, tramadol was the second most commonly prescribed analgesic comprising 9%, codeine the third most (7%), and dextropropoxyphene the fourth (5%). The proportion of NSAIDs and weak opioids and the proportion of the different weak opioids prescribed showed no change over time. The proportion of nonselective and selective NSAIDs prescribed changed; Coxib prescriptions decreased from 9% to 4% of all analgesics prescribed in 2004-2007 with no change in 2008. NSAIDs were found to be the dominant class of analgesic prescribed by primary care physicians to patients diagnosed as musculoskeletal pain. No change was observed in the proportion of NSAID and weak opioid prescription over the period studied. Prescription of selective Coxibs decreased and was less than 4% in 2008. The impact on gastrointestinal and cardiovascular adverse effects associated with the extensive prescription of NSAIDS for musculoskeletal pain warrants further analysis.
    Journal of Pain Research 08/2010; 3:131-5.
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