Effects of combination treatment with ketoprofen 100 mg + acetaminophen 1000 mg on postoperative dental pain: A single-dose, 10-hour, randomized, double-blind, active- and placebo-controlled clinical trial.

摘要

Background: A combination of analgesic drugs with different pharmacologic properties may be more effective, with fewer adverse events, than either agent used alone. Objective: This study assessed whether the combination of acetaminophen and ketoprofen is more effective and better tolerated than either drug used alone in treating postoperative pain. Methods: This single-dose randomized, double-blind, active- and placebo-controlled study was conducted at the Finnish Student Health Service, Oulu, Finland. Patients aged 18 to 40 years with moderate or severe pain (>/=3 on a numerical rating scale [NRS] of 0-10) after surgical removal of impacted third molars were randomly assigned to receive one of the following drugs in single oral doses: ketoprofen 100 mg + acetaminophen 1000 mg, ketoprofen 100 mg, acetaminophen 1000 mg, or placebo tablets. Effectiveness was assessed by the onset of analgesia, pain intensity difference (PID) from baseline, sum of PID (SPID), and duration of analgesic effect. Patients rated pain intensity on the NRS at rest and on dry swallowing. Onset of pain relief was measured using time to PID in >/=1 category at rest or on dry swallowing (PID >/=1). Patients recorded the occurrence of adverse events and the supplemental consumption of rescue medication (ibuprofen). Results: The study included 76 patients, accounting for 78 cases (2 patients were operated on twice and were assessed as 4 individual patients) (59% women, 41% men; mean age, 22.8 years; white race, 100%; and mean weight, 68.3 kg). At 1.5 hours, mean SPIDs at rest and on swallowing were significantly greater in the combination group than in the acetaminophen, ketoprofen, and placebo groups (all, P < 0.05). Mean time to onset of pain relief (PID >/=1) at rest and on swallowing were significantly less in the combination group than the acetaminophen, ketoprofen, and placebo groups (all, P < 0.05). Median time to use of rescue medication was significantly longer in the combination group than in the acetaminophen group (P = 0.006) and the placebo group (P < 0.001) but not the ketoprofen group. At 1.5 hours after administration, maximum sedation scores were not significantly different between the study groups. The prevalences of trismus, bleeding, and edema were not significantly different between the study groups. Conclusions: The results from this study suggest that the combination of ketoprofen 100 mg + acetaminophen 1000 mg provided a significantly more rapid onset of analgesia than either drug given alone in the management of pain after oral surgery in this patient population. Adverse events were not significantly different between the study groups. These results support the clinical practice of combining ketoprofen with acetaminophen for the management of acute pain.