Arthur Jeske DMD, PhD; James Zahrowski DMD, MS, PharmD
A single dose of etoricoxib (120 mg) provides good relief of post-surgical moderate to severe postoperative pain in two-thirds of adults with mild adverse effects similar to those of placebo.
High quality evidence supports etoricoxib as an effective analgesic for acute adult postoperative pain relief over 20 hours.
Is a single dose of etoricoxib an effective analgesic for treatment moderate-to-severe postoperative pain?
The authors of this Cochrane systematic review searched 4 electronic data bases that included studies up to December 2008. They followed a defined protocol using 2 independent reviewers who both assessed the quality of the trials and extracted data. They included studies of adults (aged 15 years or older) who experienced moderate-to-severe postoperative pain after surgery. They defined pain relief as a reduction in pain of at least 50% over 6 hours. The number of participants who required rescue medication was used to calculate the number needed to treat (NNT) with 95% confidence levels. The numbers of patients who had adverse effects and who withdrew were used to calculate the medication relative risk (RR). The authors used median time to needed rescue medication to calculate the duration of analgesic relief.
A review of 5 double-blind, randomized controlled studies totaling 880 participants evaluated single doses of etoricoxib or placebo. Etoricoxib (120 mg), controlled with placebo, was reported in 5 studies (655 patients). At least 50% reduction in pain was reported by 64% of participants using etoricoxib (120 mg), 10% with placebo, and the NNT was 1.9 (1.7 to 2.1). For included dental studies only, the NNT was 1.6 (1.5 to 1.8). Two studies (249 participants) that used etoricoxib at doses of 180 mg and 240 mg reported a trend with increased pain relief without a confirmed dose response relationship. The median time of rescue medication was 20 hours. Short-term adverse events were reported at a similar rate as with placebo, with no serious events.
A single oral dose of etoricoxib (120 mg) produces effective postsurgical pain relief. The 120 mg dose is as effective as, or better than, other commonly used analgesics.
Source of Funding:
Internal sources: Pain Research Funds, UK. External sources: NHS Cochrane Collaboration Programme Grant Scheme, UK.
Importance and Context:
Etoricoxib, a selective cyclo-oxygenase-2 (COX-2) inhibitor which is unavailable in the United States, is prescribed for the relief of chronic pain in osteoarthritis and rheumatoid arthritis, and for the relief of acute pain. Selective COX-2 inhibitors are associated with fewer upper gastrointestinal adverse effects than conventional nonsteroidal anti-inflammatory drugs (NSAIDs). In 2004, COX-2 inhibitors were reported to increase the risk of heart attack, thrombosis and stroke dependent upon dose and duration of use. Precautionary warnings have been placed on all NSAIDs, selective COX-2 and nonselective COX inhibitors. Because acute postoperative pain is a manifestation of inflammation due to tissue injury, a systematic review of current evidence enables evaluation of the efficacy and safety of etoricoxib as an acute postoperative analgesic.
Strengths and Weaknesses of the Systematic Review:
This high-quality systematic review included a comprehensive search with defined inclusion and exclusion criteria and no language restrictions. The authors also manually searched reference lists of retrieved studies. However, they did not search abstracts, conference proceedings and gray literature, nor did they contact any pharmaceutical manufacturers. Two authors independently assessed trial quality. Disagreements were resolved by consensus or a third author. The authors used QUOROM guidelines for data analysis and performed standard tests for homogeneity. The conclusion that “120 mg dose is as effective as, or better than, other commonly used analgesics” is unsupported, since no comparative evidence was evaluated. Authors stated they received outside remuneration unrelated to this work.
Strengths and Weaknesses of the Evidence:
All 5 included studies were double-blind, randomized controlled trials of very high quality. Four studies enrolled participants with dental pain after molar extraction. All studies had reported adverse events, withdrawals, exclusions, and missing data. No withdrawals due to adverse events were reported. There was insufficient data to examine the effect of dosage on efficacy or duration of action. Long-term, multiple dose epidemiological studies would provide a more accurate assessment of adverse drug effects.
Implications for Dental Practice:
FDA Advisory Committee in 2007 determined that the cardiovascular risks of etoricoxib outweighed benefits for chronic pain in patients at risk of thromboembolism. Etoricoxib is currently not available in the United States, Based on their effectiveness and low cost, over-the-counter NSAIDs like ibuprofen are suggested as primary analgesics for post-surgical moderate-to-severe pain instead of COX-2 inhibitors. (1) Selective COX-2 inhibitors are contraindicated in patients with ischemic heart disease or stroke, but remain a viable choice in patients with low cardiovascular risk factors and increased risk of gastrointestinal complications. Dentists continually should evaluate newer selective COX-2 inhibitors for more effectiveness and safety than established over-the-counter NSAIDs.
REFERENCES: 1. Ong CKS, Lirk P, Tan CH, Seymour RA. An Evidence-Based Update on Nonsteroidal Anti-Inflammatory Drugs. Clinical Medicine & Research 2007; 5(1):19 -34 [DOI:10.3121/cmr.2007.698]