Analgesic efficacy of bromfenac, ibuprofen, and aspirin in postoperative oral surgery pain.

We recently demonstrated that 25 mg of bromfenac, a new nonsteroidal anti-inflammatory analgesic, is at least as effective as 400 mg of ibuprofen in relieving postoperative oral surgery pain. Our objective in this study was to determine whether higher doses were significantly more effective. Two hundred eighty (280) outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned, on a double-blind basis, a single oral dose of 10, 25, 50, or 100 mg bromfenac; 650 mg aspirin; 400 mg ibuprofen; or placebo. Subjects rated their pain and its relief for 8 hours. All active treatments were significantly superior to placebo, and bromfenac and ibuprofen were significantly superior to aspirin. The slope of the dose-response curve of bromfenac was significant. The 100 mg bromfenac dose was significantly more effective than the 400 mg ibuprofen dose and had a significantly longer duration of analgesic action.

Effect of caffeine on ibuprofen analgesia in postoperative oral surgery pain.

Recent studies have demonstrated that caffeine acts as an analgesic adjuvant when combined with acetaminophen, aspirin, or their mixture. Our objective was to determine whether similar enhancement of analgesia could be demonstrated when caffeine is combined with ibuprofen. On a double-blind basis, a single oral dose of ibuprofen (50, 100, or 200 mg), a combination of ibuprofen, 100 mg, with caffeine, 100 mg, a combination of ibuprofen, 200 mg, with caffeine, 100 mg, or placebo was randomly assigned to 298 outpatients with postoperative pain after the surgical removal of impacted third molars. With a self-rating record, subjects rated their pain and its relief hourly for 8 hours. All active treatments were significantly superior to placebo, and the caffeine effect was significant for every measure of analgesia. Relative potency estimates indicated that the combination was 2.4 to 2.8 times as potent as ibuprofen alone. The combination also had a more rapid onset and longer duration of analgesic action. The analgesic adjuvancy of caffeine clearly extends to combinations with nonsteroidal anti-inflammatory drugs other than acetaminophen or aspirin.

An evaluation of the analgesic efficacy of proquazone and aspirin in postoperative dental pain.

The analgesic efficacy of 75, 150, and 300 mg proquazone, a new nonsteroidal antiinflammatory agents, was compared to that of 650 mg aspirin and a placebo in outpatients who had moderate or severe pain following the surgical removal of impacted third molars. Estimates of the relative potency of proquazone to aspirin ranged from 4.9 to 6.2 for total analgesic effect and from 7.7 to 8.4 for peak analgesic effect. Each dosage level of proquazone and aspirin provided significant analgesia compared to placebo and was well tolerated. Adverse effects were transitory and did not appear to be dose related for proquazone.

A 12-hour evaluation of the analgesic efficacy of diflunisal, aspirin, and placebo in postoperative dental pain.

Two-hundred and one outpatients with postoperative pain following oral surgery were randomly assigned, on a double-blind basis, a single oral dose of diflunisal (250, 500, or 1000 mg), aspirin (650 mg), or placebo. Using a self-rating record, the subjects rated their pain and its relief hourly for 12 hours after medication. Measures of peak and total analgesia were derived from the patients' subjective reports. Diflunisal 250 and 1000 mg were significantly superior to aspirin for every measure of total and peak analgesia; the 500-mg diflunisal dose was significantly superior to aspirin for measures of total analgesia only. All doses of diflunisal were significantly superior to aspirin and placebo at each hour from hour 3 through hour 12. Approximately 60 per cent of the patients treated with diflunisal completed the 12-hour observation period without the need for additional analgesic therapy. Adverse effects were mild and transitory and occurred in less than 10 per cent of the patients.

A method for the 12-hour evaluation of analgesic efficacy in outpatients with postoperative oral surgery pain. Three studies of diflunisal.

We have developed a method for measuring the efficacy of a single dose of an analgesic for 12 hours after administration of outpatients with postoperative oral surgery pain. Using a self-rating record, patients evaluate their pain and its relief for 12 hours after medication. We have used this method successfully in a series of three studies to compare diflunisal, a new nonsteroidal antiinflammatory analgesic, with placebo and aspirin 650 mg, acetaminophen 600 mg, propoxyphene napsylate 100 mg, or a combination of acetaminophen with either codeine 60 mg or propoxyphene 100 mg. Diflunisal evinced an unusually long duration of analgesic effect. In each study, all doses of diflunisal were significantly superior to placebo through the end of the 12-hour observation period, while the standards were superior for periods ranging from 2 to 7 hours. In terms of peak analgesia, diflunisal 1,000 mg was comparable to the acetaminophen-codeine combination and was significantly superior to all the other analgesic standards.

Evaluation of ketorolac, aspirin, and an acetaminophen-codeine combination in postoperative oral surgery pain.

One-hundred twenty-eight outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned, on a double-blind basis, to receive oral doses of ketorolac tromethamine 10 mg, aspirin 650 mg, a combination of acetaminophen 600 mg plus codeine 60 mg, or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 6 hours after medicating. All active medications were significantly superior to placebo. The acetaminophen-codeine combination was significantly superior to aspirin for peak analgesia. Ketorolac was significantly superior to aspirin for every measure of total and peak analgesia, and significantly superior to acetaminophen-codeine for measures of total effect. The analgesic effect of ketorolac was significant by hour 1 and persisted for 6 hours. Repeat-dose data also suggested that ketorolac 10 mg was superior to aspirin 650 mg and acetaminophen-codeine on the day of surgery. Differences among the active medications were trivial for the postoperative days 1-6 analyses. The frequency of adverse effects was over 4 times greater for acetaminophen-codeine than for ketorolac or aspirin.

Evaluation of ketorolac, ibuprofen, acetaminophen, and an acetaminophen-codeine combination in postoperative oral surgery pain.

Two-hundred six outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned on a double-blind basis to receive oral doses of ketorolac tromethamine 10 and 20 mg, ibuprofen 400 mg, acetaminophen 600 mg, a combination of acetaminophen 600 mg plus codeine 60 mg, or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 6 hours after medicating. All active medications were significantly superior to placebo. Analgesia was similar for ketorolac 10 and 20 mg and ibuprofen 400 mg; however, these treatments were superior to acetaminophen alone and the acetaminophen-codeine combination. The analgesic effect of each active medication was significant by hour 1 and persisted for 5-6 hours. The data suggest a plateau in ketorolac's analgesic efficacy at the 10-mg level. Repeat-dose data indicated that on the day of surgery ketorolac 10 and 20 mg and ibuprofen 400 mg were superior to acetaminophen 600 mg; ketorolac 20 mg was also superior to acetaminophen-codeine. Differences among active medications were not significant when data for the entire postoperative period (days 0-6) were evaluated. The frequency of adverse effects was similar for the active medications.

Evaluation of an ibuprofen controlled-release tablet and placebo in postoperative oral surgery pain.

Seventy-four outpatients with postoperative pain after oral surgery were randomly assigned, on a double-blind basis, to receive a single oral dose of a controlled-release tablet (CRT) containing 600 mg ibuprofen, two 600-mg ibuprofen CRTs, or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 12 hours after medicating. Estimates of total and peak analgesia were derived from these subjective reports. The ibuprofen CRTs (600 and 1200 mg) had manifested an analgesic effect by hour 1 and their efficacy persisted for 12 hours. Comparable effect for the two ibuprofen CRT dosages could suggest a plateau in analgesia at the 600-mg level or a lack of upside assay sensitivity. Duration of effect was longer for the CRTs than we have previously observed with conventional ibuprofen tablets. Adverse effects were transitory and consistent with the known pharmacologic profile of the medication evaluated.

Analgesic effect of an aspirin-codeine-butalbital-caffeine combination and an acetaminophen-codeine combination in postoperative oral surgery pain.

The efficacy of an aspirin-caffeine-codeine-butalbital combination was compared to an acetaminophen-codeine combination and placebo in outpatients who had moderate or severe pain after the surgical removal of impacted third molars. Using a self-rating record, patients rated their pain, relief, anxiety and relaxation hourly for up to 6 hours after medicating. Each active medication was significantly superior to placebo for measures of analgesia and relaxation. Although the butalbital-containing combination provided consistently greater analgesia, the differences between active medications were not statistically significant. The acetaminophen-codeine combination significantly reduced anxiety; however, the butalbital containing combination did not. The results of this study suggest that female patients may have greater efficacy than male patients. All adverse effects were transitory and consistent with the known pharmacologic profiles of the study medications or the backup analgesic.

Evaluation of bromfenac, aspirin, and ibuprofen in postoperative oral surgery pain.

Two hundred forty-one outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned, on a double-blind basis, to receive a single oral dose of bromfenac 5, 10, or 25 mg, aspirin 650 mg, ibuprofen 400 mg, or placebo. Using a self-rating record, subjects rated their pain and its relief for 8 hours after medicating. Estimates of summed pain intensity difference, peak pain intensity difference, total relief, peak relief, and hours of 50% relief were derived from these subjective reports. All active treatments were significantly superior to placebo, and the slope of the dose-response curve for bromfenac was significant. Bromfenac 5 mg and aspirin 650 mg were equianalgesic; bromfenac 25 mg was slightly more efficacious than ibuprofen 400 mg. Bromfenac 25 mg and ibuprofen 400 mg were significantly superior to the other active treatments. Adverse effects were transient and consistent with the pharmacologic profiles of the medications evaluated.

A 12-hour evaluation of the analgesic efficacy of diflunisal, zomepirac sodium, aspirin, and placebo in postoperative oral surgery pain.

One hundred ninety-nine outpatients with pain following oral surgery were randomly assigned, on a double-blind basis, a single oral dose of diflunisal (500 or 1,000 mg), zomepirac sodium 100 mg, aspirin 650 mg, or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 12 hours after medication. Measures of total and peak analgesia were derived from these patients' subjective reports. Diflunisal (500 and 1,000 mg) and zomepirac were significantly superior to aspirin and placebo for every measure of total and peak analgesia. Based upon the first 4 hours of observation, aspirin was superior to placebo for every measure of analgesia. Diflunisal 500 and 1,000 mg were comparable to zomepirac in peak analgesia and significantly superior to zomepirac for all measures of total analgesia. The onset of analgesia was comparable for 1,000 mg diflunisal, zomepirac, and aspirin, but more rapid for these treatments than for 500 mg diflunisal. The duration of analgesia was 12 hours for diflunisal, 9 hours for zomepirac, and 3 hours for aspirin.

Evaluation of flurbiprofen, acetaminophen, an acetaminophen-codeine combination, and placebo in postoperative oral surgery pain.

Eighty-eight outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned, on a double-blind basis, to receive a single, oral dose of flurbiprofen 100 mg, acetaminophen 600 mg, a combination of acetaminophen 600 mg with codeine 60 mg, or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 12 hours after medicating. Estimates of sum of pain intensity differences, peak pain intensity differences, total relief, peak relief, and hours of 50% relief were derived from these subjective reports. Flurbiprofen and the acetaminophen-codeine combination were significantly superior to placebo for every measure of total and peak analgesia and significantly superior to acetaminophen alone for most measures of efficacy. Based on the 12-hour data, acetaminophen alone did not differ significantly from placebo; however, it was superior to placebo for measures of total effect based on the 4-hour data. Flurbiprofen was significantly superior to the acetaminophen codeine combination with respect to the number of hours until remedication. All medications had manifested an effect by hour 1; analgesia persisted for 12 hours for flurbiprofen, 6 hours for acetaminophen-codeine, and 3 hours for acetaminophen alone. The frequency of adverse effects was similar for the active medications.

Analgesic effect of naproxen sodium, codeine, a naproxen-codeine combination and aspirin on the postoperative pain of oral surgery.

In a double-blind study, 198 outpatients with pain after oral surgery were randomly assigned to treatment with a single oral dose of naproxen sodium 550 mg, codeine sulfate 60 mg, a combination of naproxen sodium 550 mg with codeine sulfate 60 mg, aspirin 650 mg or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 12 hours after medication. Orthogonal contrasts for the four treatments making up the factorial component showed that the naproxen effect was significant for every measurement of total and peak analgesia; the codeine effect was significant for total and peak pain relief and patients' overall evaluation. The naproxen-codeine interaction was not statistically significant for any measure, which suggests that the analgesic effect of the combination represents the additive effect of its constituents. Based on pairwise comparisons, aspirin was significantly superior to placebo for most measures of effect, naproxen was significantly superior to both aspirin and codeine for all measures and the combination was significantly superior to naproxen for patients' overall evaluation. No more patients experienced adverse effects with aspirin or naproxen than with placebo, but significantly more patients receiving the codeine-containing treatments experienced adverse effects than those receiving aspirin and naproxen.

Evaluation of two opioid-acetaminophen combinations and placebo in postoperative oral surgery pain.

STUDY OBJECTIVE: To determine the relative analgesic potency and adverse effect liability of hydrocodone bitartrate 7.5 mg with acetaminophen 500 mg, codeine phosphate 30 mg with acetaminophen 300 mg, and placebo in the treatment of pain following oral surgery. DESIGN: Randomized, double-blind, single-dose, placebo-controlled, parallel-group study with self-ratings at 30 minutes and then at hourly intervals from hour 1 to hour 6. SETTING: Private, oral surgery practice sites. PATIENTS: Three hundred twenty-four outpatients with moderate or severe pain after the surgical removal of impacted third molars were selected. One was lost to follow-up and 32 did not need an analgesic; 232 patients had valid efficacy data. INTERVENTIONS: Patients were treated with a single oral dose of hydrocodone bitartrate 7.5 mg with acetaminophen 500 mg, codeine phosphate 30 mg with acetaminophen 300 mg, or placebo when they experienced steady, moderate or severe pain that, in their opinion, required an analgesic. Using a self-rating record, subjects rated their pain and its relief for 6 hours after medicating; estimates of peak and total analgesia were derived from these subjective reports. MEASUREMENTS AND MAIN RESULTS: This study was a valid analgesic assay. Both active treatments were significantly superior to placebo for all measures of analgesic efficacy. The hydrocodone-acetaminophen combination was significantly superior to the codeine-acetaminophen combination for total pain relief and the number of evaluations with 50% relief. Both active treatments manifested an analgesic effect within 30 minutes; the effect persisted for 5 hours for the codeine combination and 6 hours for the hydrocodone combination. Adverse effects were transient, consistent with the pharmacologic profiles of opioids, and none required treatment. CONCLUSIONS: A slight advantage in analgesic efficacy was demonstrated in this single-dose study for the hydrocodone-acetaminophen combination. Repeat-dose studies, however, should be conducted to determine the clinical significance of the difference in analgesic effect of these opioid combinations.

Evaluation of aspirin, caffeine, and their combination in postoperative oral surgery pain.

Three hundred fifty outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned, on a double-blind basis, to receive a single oral dose of aspirin 650 or 1000 mg, caffeine 65 mg, a combination of aspirin 650 mg with caffeine 65 mg, or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 6 hours after medicating. Estimates of summed pain intensity difference, peak pain intensity difference, total relief, peak relief, and hours of 50% relief were derived from these subjective reports. All active treatments except caffeine were significantly superior to placebo. Pairwise comparisons indicated the aspirin-caffeine combination was statistically superior to aspirin 650 mg alone for hours of 50% relief among patients who had severe baseline pain. Adverse effects were transitory and none were serious.

An evaluation of the analgesic efficacy of three opioid-analgesic combinations in postoperative oral surgery pain.

The analgesic efficacy of a hydrocodone-acetaminophen combination, a codeine-acetaminophen combination, a codeine-APC (aspirin, phenacetin, and caffeine) combination, and a placebo was evaluated in outpatients who had moderate or severe pain after the surgical removal of impacted third molars. Each of the active medications had a significant effect on essentially all measures of total and peak analgesia; they did not differ significantly on any measure of analgesia. Adverse effects were transitory and, in general, appear to have been related to the centrally acting component of each combination analgesic.

Diflunisal. A new oral analgesic with an unusually long duration of action.

The analgesic efficacy of single 500- and 1,000-mg doses of diflunisal (Dolobid), a new nonsteroidal anti-inflammatory analgesic, was compared in a double-blind study with that of acetaminophen, 600 mg, the combination of acetaminophen, 600 mg, with codeine phosphate, 60 mg, and placebo in 159 oral surgery outpatients. Using a self-rating record, patients rated their pain and its relief hourly for 12 hours after medication. Both doses of diflunisal were significantly more effective than acetaminophen alone and produced peak analgesia comparable to that of the acetaminophen-codeine combination. Diflunisal proved to have an unusually long duration of analgesic action. Acetaminophen and the combination were significantly superior to placebo through hours 2 and 5, respectively; both doses of diflunisal were significantly superior through the end of the 12-hour observation period. None of the active treatments produced more side effects than the placebo.