Arthur Jeske DMD, PhD
Adequate-quality but limited evidence suggests single-dose etodolac effectively reduces acute moderate to severe postoperative pain in adults with minimal adverse effects.
For adults with acute moderate to severe postoperative pain, what is the efficacy and safety of a single oral dose of etodolac compared to placebo?
This Cochrane systematic review of all studies to May, 2009 utilized four electronic databases. A clear protocol was followed with two independent authors assessing trial quality and extracting data. Pain relief or pain intensity data were extracted to determine the number of participants who experienced 50% or more pain relief within a 4 to 6-hour period after a single oral dose of etodolac. Number-needed-to-treat (NNT) and relative risk were calculated as measures of efficacy. Adverse events and the need for rescue medication were evaluated as secondary outcome measures.
A review of 9 adequate-quality studies (1,764 participants) evaluated the analgesic effect of doses of etodolac from 25 mg to 1,200 mg, with most information reported for 50 mg, 100 mg and 200 mg. For at least 50% pain relief compared with placebo the NNT for etodolac 50 mg (360 participants) was 8.3 (29% vs. 17% with placebo). For etodolac 100 mg (498 participants), the NNT was 4.8 (41% vs. 20% with placebo), and for etodolac 200 mg (670 participants) the NNT was 3.3 (44% vs. 13% with placebo). In studies with 200 mg doses, 64% of participants required rescue medication in 6 to 8 hours and 63% with 400 mg doses. There were insufficient data to analyze the time to need for rescue medication. Adverse events were uncommon and did not differ from placebo.
Etodolac 200 mg provides a high level of pain relief in about 40% of patients with moderate or severe postoperative pain. This is fewer that the same level of pain relief with standard doses of ibuprofen, naproxen and diclofenac. Higher doses may be required to achieve outcomes seen with standard doses of other NSAIDs.
Source of Funding:
Internal sources: Pain Research funds, UK. External sources: NHS Cochrane Collaboration Programme Grant Scheme, UK, NIHR Biomedical Research Centre Programme, UK.
Importance and Context:
Because etodolac is relatively more selective for inhibition of the COX-2 isoform of cyclooxygenase, it could be of benefit for the management of post-operative pain control in adults who may not tolerate the adverse gastrointestinal effects of more traditional, non-selective agents, such as ibuprofen, especially if it were as effective as the traditional, non-selective drugs. Studies of the effectiveness and safety of selective COX-2 inhbitors, including etodolac, should help clinicians select appropriate pain-control regimens. Additionally, COX-2 selective inhibitors are not recommended for use in patients who are at risk for complications of thromboembolism (1).
1. Antman EM, Bennett JS, Daugherty A, Furberg C, Roberts H, Taubert KA. Use of nonsteroidal anti-inflammatory drugs: an update for clinicians--a scientific statement from the American Heart Association. Circulation 2007;115(2):1634-1642.
Strengths and Weaknesses of the Systematic Review:
This high-quality systematic review included a comprehensive search, defined inclusion and exclusion criteria, and no language restrictions. The manufacturing pharmaceutical companies were not contacted for unpublished trial data. Two authors independently assessed trial quality and extracted data with disagreements resolved through consensus or by a third author. Standard guidelines for data analysis and heterogeneity were followed. Etodolac treatment parameters which may affect pain relief, such as dose per subject weight, timing of dose related to the procedure, and multiple dose administrations were not evaluated. The authors acknowledged receipt of consultation support and lecture fees from unnamed pharmaceutical companies.
Strengths and Weaknesses of the Evidence:
The included studies were all randomized and double-blinded to minimize bias, although more robust reviews of single-dose, postoperative analgesia have included far greater numbers of studies and participants. The majority of studies evaluated single etodolac doses of 25 to 1,200 mg. Reporting of data for adverse events and participant withdrawals were not always complete. Single-dose studies are of limited value for assessing the incidence of adverse effects.
Implications for Dental Practice:
Current evidence from high-quality systematic reviews continues to favor the use of traditional, non-selective NSAIDs as drugs of first choice for moderate to severe postoperative pain. While COX-2-selective agents such as etodolac and celecoxib offer fewer side effects when used long-term, their comparative lesser efficacy and greater cost militate against their routine use in dentistry. They are also the least desirable analgesics for use in patients at risk of complications of thromboembolism (1).
1. Antman EM, Bennett JS, Daugherty A, Furberg C, Roberts H, Taubert KA. Use of Nonsteroidal Antiinflammatory Drugs, An Update for Clinicians: A Scientific Statement From the American Heart Association. Circulation. 2007;115:1634-1642.