Arthur Jeske DMD, PhD; James Zahrowski DMD, MS, PharmD
Good evidence suggests that single doses of both ketoprofen at 25 and 50 mg and of dexketoprofen at 10 to 25 mg effectively reduce 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 ketoprofen or dexketoprofen as compared with placebo?
In this Cochrane systematic review of studies to August 2009, the authors searched four electronic databases. They followed a clear protocol, with two independent authors assessing trial quality and extracting data. They extracted pain relief or pain intensity data to determine the number of participants who experienced 50 percent or greater relief over four to six hours after receiving a single oral dose of ketoprofen or dexketoprofen. The authors calculated the number needed to treat (NNT) and relative risk as measures of efficacy. They also reported the need for and time to the use of rescue medication.
The review compared the analgesic effects of ketoprofen (11 studies, 968 participants) and placebo (542 participants) and dexketoprofen (seven studies, 681 participants) and placebo (289 participants). The majority of studies, which were of high quality, evaluated ketoprofen at 25- and 50- milligram doses. To achieve at least 50 percent pain reduction across four to six hours, the NNTs for ketoprofen were 2.4 to 3.3 at doses between 12.5 mg and 100 mg, with better values for dental-only studies (2.4 to 1.6). For dexketoprofen at 10/12.5 mg to 20/25 mg, NNTs were 3.6 to 3.2, respectively, across four to six hours, with no evident dose response. Remedication time was about five and four hours for ketoprofen and dexketoprofen, respectively, and significantly lower than placebo. The expected equivalent efficacy with 50 percent lower doses of dexketoprofen was not demonstrated. Adverse effects were uncommon and did not differ from placebo.
A limited amount of high-quality evidence demonstrates that ketoprofen between 25- and 100 mg-doses is an effective analgesic for moderate-to-severe postoperative pain. At a dose of ketoprofen 50 mg, the NNT was 3.3, an efficacy intervention rate similar to commonly used NSAIDS. The duration of action was about five hours. Dexketoprofen cannot be recommended as a better-tolerated, alternative analgesic to ketoprofen. Both drugs were well tolerated in single doses.
Source of Funding:
Internal Sources: Oxford Pain Research Funds, UK. External sources: NHS Cochrane Collaboration Programme Grant Scheme, UK, NIHR Biomedical Research Centre Programme, UK.
Importance and Context:
As first-choice agents for managing dental pain, nonselective nonsteroidal anti-inflammatory drugs (NSAID) offer significant advantages over opioids, particularly in that they do no impair consciousness and some are available over-the-counter. As such, the safety and efficacy of ketoprofen should be assessed. In turn, if the therapeutic equivalence of the (S)-enantiomer (dexketoprofen) is established, it may result in fewer adverse effects.
Strengths and Weaknesses of the Systematic Review:
This high-quality systematic review included a comprehesive search, defined inclusion and exclusion criteria, and had no language restrictions. The authors did not search abstracts, conference proceedings or other grey literature, but they did include unpublished information from the marketer of dexketoprofen. Two authors independently assessed trial quality and extracted data. Disagreements were resolved through consensus or by a third author. The authors followed standard guidelines for data and heterogeneity analysis. They did not evaluate variables that could affect pain relief, such as timing of dose relative to procedure. The authors acknowledged support from government and industry sources.
Strengths and Weaknesses of the Evidence:
The review included 18 studies (3,785 participants) that were predominantly of high quality, all of which were randomized and double-blinded to minimize bias. Most of the studies evaluated single doses of ketoprofen. The other studies, fewer in number, evaluated various dosage amounts of dexketoprofen. There was considerable heterogeneity in the non-dental studies. Reporting of adverse event data, withdrawals and exclusions, and handling of missing data was not always complete.
Implications for Dental Practice:
Good evidence supports that a single dose of ketoprofen safely provides relief with minimal adverse effects in adults who have moderate-to-severe pain. Larger doses appear to increase efficacy and duration of analgesia. As with other NSAIDs, ketoprofen is contraindicated by allergy to NSAIDs, pregnancy, and in patients receiving low-dose aspirin as stroke prevention. (1). More studies are needed to establish safety profile over longer durations of time.
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;11:1634-1642.