Arthur Jeske DMD, PhD; James Zahrowski DMD, MS, PharmD
A single dose of diflunisal (500 to 1000 mg) effectively relieves pain for 12 hours in adults with acute moderate-to-severe pain symptoms.
This high-quality review of nine random controlled trials (RCTs) found that diflunisal is an effective analgesic that causes mild adverse effects at higher doses (1000 mg).
For acute moderate-to-severe postoperative pain in adults, is a single dose of diflunisal as compared to placebo an effective and safe analgesic?
The authors searched four electronic databases to January 2010. They followed a defined protocol. Two independent reviewers both assessed the quality of the trials and extracted data. Efficacy was defined as 50 percent or greater pain relief over four to six hours from a single dose of diflunisal. The number needed to treat (NNT) was calculated with 95 percent confidence levels from numbers requiring rescue medication. Numbers of participants using rescue analgesia over a specified time period and time-to-use were sought as measures of duration of analgesia. The authors also collected data on adverse events and withdrawals.
The authors included nine random controlled trials in which a total of 1,420 participants each received a single dose of diflunisal ranging from 125 to 1000 mg.
For diflusinal at 1000 mg, in six studies (391 participants) the authors calculated the number needed to treat (NNT) for at least 50 percent pain relief over four to six hours as 2.1 (1.8 to 2.6). In six studies (409 participants), the NNT to prevent remedication was 1.9 (1.7 to 2.3) and 2.2 (1.9 to 2.7) within six and 12 hours, respectively.
For diflunisal 500 mg, in six studies (357 participants) the NNT was 2.6 (2.1 to 3.3) for at least 50 percent pain relief over 4 to 6 hours. The NNT to prevent remedication within six and 12 hours was 2.6 (2.1 to 3.4) in six studies (390 participants) and 2.9 (2.3 to 4.0) in five studies (329 participants), respectively.
For diflunisal 125 mg and 750 mg, the data were insufficient for analysis.
More participants experienced adverse events with diflunisal 1000 mg than with placebo, but none was serious or led to withdrawal. For diflunisal 500 mg, the adverse events did not differ significantly from placebo.
Diflunisal has a good analgesic effect similar to other NSAIDs in single dose with a duration of about 12 hours. This property may be useful when regular dosing is needed, or when taking several doses of a shorter acting analgesic is impractical.
Source of Funding:
Oxford Pain Research Funds, UK., NHS Cochrane Collaboration Grant, UK.,NIHR Biomedical Research Centre Programme, UK.
Importance and Context:
Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly prescribed analgesic medications worldwide and their efficacy for treating acute pain has been well demonstrated. (1) Diflunisal is a NSAID derived from aspirin, but it has no acetyl group. Therefore, diflunisal has a reversible effect to inhibit platelet function which increases bleeding time. The drug half-life (eight to 12 hours) of diflunisal allows twice daily administration, but has a slower onset of analgesia. The efficacy and adverse effects of single dose oral diflunisal for acute postoperative pain needs to be evaluated to permit comparison with other analgesics.
Strengths and Weaknesses of the Systematic Review:
The authors conducted a high-quality systematic review that included a comprehensive search with defined inclusion and exclusion criteria with no language restrictions. They manually searched reference lists of retrieved studies. They did not search abstracts, conference proceedings and grey literature nor did they contact any pharmaceutical manufacturers. Two authors used QUOROM guidelines for data analysis and performed standard heterogeneity tests. The authors have declared receiving contributions for lectures, consultations and research with unnamed pharmaceutical companies, charities, government and industry sources unrelated to this work.
Strengths and Weaknesses of the Evidence:
Eight of the nine studies were both randomized and double blind with high scores for methodological quality. The authors excluded one questionable study from analyses, but that did not change the results. Studies both recruited participants with adequate baseline pain and used clinically useful outcome measures. Individual studies were small, but pooled data provided sufficient information, particularly at the 500 and 1000mg doses, for reliable estimates of efficacy outcomes. Adverse event data were not well reported, with little information on how the data were collected.
Implications for Dental Practice:
Diflunisal (500 to 1000mg) effectively relieves acute pain following dental procedures with minimal adverse effects at higher doses. Diflunisal also possesses the advantage of a longer duration of analgesia than other NSAIDs. Nonprescription NSAIDS should be considered first due to their comparable effective pain relief and lower cost. Diflunisal, as with other NSAIDs, is not recommended if patients are allergic to NSAIDs or aspirin, or are pregnant, or have active gastrointestinal bleeding, or taking daily low dose aspirin (coronary heart disease or stroke prevention). (2) 1.Ong CK, Lirk P, Tan CH, Seymour RA. An evidence-based update on nonsteroidal anti-inflammatory drugs. Clin Med Res 2007;5(1):1934. 2.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.