The effectiveness of 100 and 200 mg etodolac (Ultradol), aspirin, and placebo in patients with pain following oral surgery

The analgesic efficacy of etodolac (Ultradol) was evaluated in 168 patients experiencing moderate to severe pain following oral surgery. The patients were given either etodolac 100 mg, etodolac 200 mg, aspirin 650 mg, or placebo. There was a minimum of forty patients in each drug group. Patients recorded pain intensity and pain relief at 1/2 hour and then hourly for up to 12 hours after medication. The efficacy variables analyzed were the sum of pain-intensity differences, total pain relief, onset of analgesia, and the patient's opinion of the study drug. Time-effect curves were made from the pain-relief and pain-intensity difference scores. The analgesic potency of both 100 and 200 mg of etodolac was comparable to 650 mg of aspirin and superior to placebo. Like aspirin, both doses of etodolac showed significant analgesia within one hour and a significantly longer duration of action than placebo.     

Comparison of etodolac, zomepirac, and placebo for relief of pain after oral surgery

A double-blind, randomized study of 137 patients compared the effectiveness of single doses of etodolac, 200 and 400 mg, zomepirac, 100 mg, and placebo in relieving moderate to severe pain following third molar extractions. Throughout the 12-hour evaluation period, doses of both etodolac and zomepirac were significantly superior to placebo for total analgesic effect, as measured by the sum of pain intensity difference (SPID) and sum of pain relief (TOTPAR) scores. However, there were no significant differences among the active drugs. It was concluded that etodolac, 200 and 400 mg, provides analgesic efficacy comparable to that of zomepirac, 100 mg, and superior to that of placebo.     

Comparative analgesic potency of aspirin and ibuprofen.

The object of a study was to evaluate the analgesic efficacy of ibuprofen for dental pain. The subjects were outpatients who were undergoing surgical removal of impacted teeth. We compared aspirin, 325 mg; aspirin, 650 mg; ibuprofen, 200 mg; ibuprofen, 400 mg; and placebo. Each patient received a single dose of one of the test medications; there was a minimum of 37 patients in each treatment group. Patients recorded pain intensity before receiving medication; then hourly, for four hours after medication, they recorded pain intensity, amount of relief, and side effects. Time-effect and dose-response curves were generated from the relief and change in pain-intensity scores. First-hour scores, peak scores, and total scores were analyzed. All active medications were significantly better than placebo and the mean effect for ibuprofen was significantly more than for aspirin.     

Double-blind evaluation of etodolac (200 mg, 400 mg) compared with zomepirac (100 mg) and placebo on third molar extraction pain

This controlled, single dose study has demonstrated that compared with placebo, substantial analgesia is obtained with 200 and 400 mg doses of etodolac. The analgesic effects of both doses of etodolac were not notably different from each other or significantly different from zomepirac, a proven analgesic. With respect to safety, both doses of etodolac were well tolerated, with no reports of serious or dose related adverse side effects.     

Analgesic activity of ibuprofen (Motrin) in postoperative oral surgical pain.

The effectiveness of 400 and 800 mg. of ibuprofen was compared to that of 650 mg. of aspirin, 65 mg. of propoxyphene HCl, and placebo in 510 patients experiencing pain subsequent to oral surgical procedures. In double-blind study, patients were randomly assigned to one of five experimental groups and instructed to report the intensity of pain (complete, partial, or none) over a 3-hour period of evaluation. Ibuprofen, at both doses, was shown to be more effective for both degree and duration of relief from pain.     

The analgesic efficacy of valdecoxib vs. oxycodone/acetaminophen after oral surgery

BACKGROUND: The authors conducted two studies to compare the analgesic efficacy and safety of the cyclooxygenase, or COX, -2-specific inhibitor, valdecoxib, with oxycodone/ acetaminophen in patients who have undergone oral surgery. METHODS: In total, 205 eligible subjects in Study A and 201 in Study B were randomized to receive a single oral dose of valdecoxib (20 or 40 milligrams), a combination of oxycodone 10 mg/acetaminophen 1,000 mg or placebo. Eligible subjects experienced moderate-to-severe pain within six hours of surgery during which two or more impacted third molars were extracted. Analgesic efficacy was assessed over 24 hours or until the patient required rescue analgesia. RESULTS: In both studies, subjects receiving either dose of valdecoxib experienced a rapid onset of analgesia and (among those who received valdecoxib 40 mg) a level of pain relief comparable with that of those who received oxycodone/ acetaminophen. Both valdecoxib doses had a significantly longer duration of analgesic effect than did oxycodone/acetaminophen. Pooled safety data demonstrated that each valdecoxib dose had a tolerability profile superior to that of oxycodone/ acetaminophen and similar to that of placebo. CONCLUSIONS: Orally administered valdecoxib is as rapidly acting and effective as oxycodone/acetaminophen, and it has a superior duration of analgesic effect in patients after oral surgery. Valdecoxib has a tolerability profile superior to that of oxycodone/acetaminophen. CLINICAL IMPLICATIONS: The current standard of care for alleviating acute pain after oral surgery has rested largely on conventional nonsteroidal anti-inflammatory drugs or opioid/analgesic combination products. The studies reported here suggest that the COX-2-specific inhibitor valdecoxib offers an efficacious and safe alternative to other analgesics used to treat pain after oral surgery.     

The optimal analgesic dose of rofecoxib: Overview of six randomized controlled trials

BACKGROUND: Rofecoxib, which specifically inhibits cyclooxygenase-2, is indicated for relief of the signs and symptoms of osteoarthritis and for the management of acute pain in adults. The authors present an overview of six placebo-controlled trials designed to evaluate the single-dose analgesic efficacy of a range of doses of rofecoxib in the treatment of postoperative dental pain. METHODS: The six studies included doses of rofecoxib ranging from 7.5 to 500 milligrams. Maximal analgesic doses of a nonsteroidal anti-inflammatory drug, or NSAID, either naproxen sodium (550 mg) or ibuprofen (400 mg), were used as active comparators in each study. Analgesic efficacy was assessed with the use of validated self-administered questionnaires. The primary endpoint in each study was the total pain relief over the eight-hour postdose period. Additional endpoints were used to characterize the onset of analgesia and peak analgesic effect. RESULTS: The results of these studies demonstrated that the efficacy of rofecoxib was dose-related, with 50 mg being consistently more effective than placebo for all measures of analgesic efficacy. Moreover, 50 mg was the lowest dose that reproducibly demonstrated an analgesic effect comparable to the effect of maximum single analgesic doses of NSAIDs. CONCLUSION: The results of these studies support the recommended dose of 50 mg of rofecoxib once daily for the management of pain. CLINICAL IMPLICATIONS: Rofecoxib, at a dose of 50 mg, is effective in the management of postoperative dental pain.     

The analgesic efficacy and safety of intra-articular morphine and mepivicaine following temporomandibular joint arthroplasty.

PURPOSE: This study was designed to evaluate the efficacy and safety of intra-articular morphine, mepivacaine, or a combination of both in the management of temporomandibular joint (TMJ) pain in a 24-hour period after arthroplasty. PATIENTS AND METHODS: This was a randomized, double-blind, prospective, parallel, placebo-controlled, single-injection study of 35 patients who underwent TMJ arthroplasty. Patients were randomized into 4 groups. Group M (morphine) received 1 mg of morphine sulfate in 1 mL of saline; group MEP (mepivicaine) received 30 mg of mepivacaine hydrochloride in 1 mL of saline; group M/MEP received 30 mg of mepivacaine hydrochloride and 1 mg of morphine in 1 mL of saline; and group C (saline control) received 1 mL of saline. Patients received a single dose of study medication when their postoperative pain reached a moderate or severe intensity and was 50 mm or greater on a 100-mm pain scale. Analgesic efficacy measures included the time to meaningful pain relief measured using a stop watch and time to rescue medication. Pain relief and pain intensity ratings were recorded at the time to relief and time to rescue medication. A global evaluation for the effectiveness of the medications was recorded within 24 hours after dosing. Adverse events were recorded and categorized by system effect. RESULTS: MEP and M/MEP were significantly more effective than placebo for all the analgesic measures. Morphine alone provided only mild analgesia and did not differ from placebo in the primary efficacy measures. The average overall pain relief was substantially better for MEP than M and M/MEP (P = .03). In patients receiving MEP, the mean time to pain relief was 2.9 minutes and the mean analgesic duration was 9.7 hours (586 minutes); 3 patients required no rescue medication in the 24 hour postdosing period. In patients receiving M/MEP, the mean time to analgesia was 7.6 minutes and the duration of analgesia was 2.7 hours (175 minutes). The average time to onset and duration of analgesia in the MEP and M/MEP groups was statistically significantly better (P < .001) then in the M alone group (17.7 minutes, 0.43 hours, respectively) and the placebo C group (16.1 minutes, 0.17 hours, respectively). At the end of the study, 80% of the patients given MEP rated the medication as a very good or excellent pain reliever, whereas only 40% of patients given M/MEP, 10% of patients given M, and no patients given placebo gave these same ratings. No serious adverse events occurred in this study. Gastrointestinal adverse events were the most common side effect noted in the MEP and M/MEP groups but were mild in intensity and reversed without treatment. CONCLUSION: All intra-articular TMJ injections of active substances provided better analgesia than placebo. Morphine alone provided only mild and short-acting analgesia. The local anesthetic, mepivacaine, given alone was safe, provided the quickest, longest acting and most effective analgesia. This proof of concept study suggests that local anesthetics are superior analgesics when given intra-articularly for postoperative TMJ surgery pain and should be investigated for dose response and multiple or continuous infusion effectiveness.     

The effectiveness of prophylactic etodolac on postendodontic pain

To determine if prophylactic etodolac would significantly reduce postendodontic pain, when compared with ibuprofen or placebo, 36 patients consented to single blind oral administration of either 400 mg of etodolac, 600 mg of ibuprofen, or a placebo, before conventional one-appointment root canal therapy. Patient-reported visual analog scale ratings of pain intensity were conducted upon initial clinical presentation, immediately postoperative, 4, 8, 12, 24, 48, and 72 h after initiation of root canal therapy. Results showed that prophylactic ibuprofen administration significantly reduced postendodontic pain at 4 and 8 h after initiation of root canal therapy, when compared with etodolac and a placebo. Patients with a periapical diagnosis of acute apical periodontitis or with a Phoenix abscess showed a significant increased need for additional medication after completion of root canal therapy, compared with all other periapical diagnoses.     

Analgesic safety and efficacy of diclofenac sodium softgels on postoperative third molar extraction pain.

PURPOSE: The purpose of this single-blind, placebo-controlled, 3-arm parallel, randomized study was to compare the analgesic efficacy and tolerability of a single dose of 100 mg diclofenac potassium (Cataflam; Novartis, Stein, Switzerland), 100 mg diclofenac sodium softgel, and placebo in patients experiencing moderate to severe postoperative pain after third molar extraction. PATIENTS AND METHODS: Seventy-five patients (67% female with a mean age of 23, age range 18 to 34.5 years) participated in the study following removal of at least 1 impacted mandibular third molar. Patients received a single dose of study medication when their postoperative pain reached a moderate or severe intensity. Analgesic efficacy measures included the time to meaningful pain relief measured using a stopwatch and time to rescue medication. Pain relief (PR) and Pain intensity (PI) ratings were recorded at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, and 24 hours postdosing. Summary analgesic measures, including Summed Pain Relief Score (TOTPAR) and Summed Pain Intensity Differences (SPID), were calculated from the 0.25- to 6-hour responses. The time between pain relief and rescue and a global evaluation for the effectiveness of the study medications were recorded at the end of the study. Seven scheduled blood samples were collected from each patient for determining plasma concentrations of diclofenac anion. RESULTS: Both diclofenac sodium softgel and Cataflam were significantly more effective than placebo (P <.0001) for all summary analgesic measures. The average overall pain relief was substantially better from diclofenac sodium softgel than from Cataflam, but the difference was not statistically significant (P =.14). In patients taking diclofenac sodium softgel, 50% of the patients experienced a time to onset of analgesic activity within 18 minutes and the median analgesic duration was 5 hours (302 minutes). Fifty percent of the patients taking Cataflam had a time to onset of action within 38 minutes, and the median duration of analgesia was 4.5 hours (272 minutes). At the time of rescue drug administration or 6 hours, whichever was earlier, 72% of the patients given diclofenac sodium softgel rated the medication as a very good or excellent pain reliever, whereas only 45% of the patients taking Cataflam gave these ratings. No serious adverse events were observed in this study. The mean concentrations of diclofenac from the diclofenac sodium softgel formulation were significantly different from the Cataflam formulation. The mean C(max) for the softgel was almost twice that of Cataflam and C(max) was reached an hour earlier, on average. CONCLUSIONS: More diclofenac anion was absorbed at a quicker rate using the formulation diclofenac sodium softgel 100 mg than Cataflam. The softgel provided a very rapid onset of analgesic activity, a prolonged analgesic duration, and an acceptable side-effect profile in the postoperative third molar surgery pain model. In an acute pain situation, the rapid absorption of nonsteroidal anti-inflammatory drugs from a formulation like the Softgel may positively affect the time of onset and duration of inflammatory pain compared with other commercially available nonsteroidal anti-inflammatory drug formulations.     

Comparison of meclofenamate sodium with buffered aspirin and placebo in the treatment of postsurgical dental pain

The efficacy of meclofenamate sodium (Meclomen) at two different doses was compared with that of buffered aspirin and placebo in the control of postsurgical pain in a double-blind, randomized study of 205 patients. Meclofenamate sodium, 200 mg, was significantly better than meclofenamate sodium, 100 mg, in some efficacy parameters. Both doses of meclofenamate sodium were superior to buffered aspirin in most parameters of efficacy, and more effective than placebo in every parameter.     

Ibuprofen controlled-release formulation: A clinical trial in dental impaction pain

This double-blind study compared a controlled-release formulation of ibuprofen 600 mg with three doses of regular ibuprofen 200 mg and three doses of codeine 30 mg. Patients who had dental impaction surgery received the controlled-release ibuprofen, codeine, or regular ibuprofen when postoperative pain reached moderate to severe intensity. At 4 and 8 hours after dose 1, patients who had initially received the controlled-release ibuprofen received a placebo, and those taking ibuprofen and codeine received their second and third doses of those drugs. All doses of study medication or placebo appeared identical for each treatment. Subjects made evaluations hourly for 12 hours in a diary. The controlled-release ibuprofen had a comparable onset to ibuprofen, a higher peak effect, and was significantly more effective than ibuprofen at hour 4; the controlled-release ibuprofen was significantly more effective than codeine for all hourly observations through hour 9. Ibuprofen was significantly better than codeine only through hour 3. The controlled-release ibuprofen had the lowest incidence of side effects and codeine the highest. The single dose of the controlled-release ibuprofen formulation appeared as efficacious as three regular doses of ibuprofen 200 mg over a 12-hour period.     

Control of pain with meclofenamate sodium following removal of an impacted molar

The analgesic effectiveness of meclofenamate sodium (Meclomen) at two dose levels, 200 mg and 100 mg, was compared with the effectiveness of a placebo and aspirin, 600 mg, in a double-blind study of 174 adult outpatients who had undergone removal of impacted third molars. When compared with the placebo, meclofenamate sodium at either dose level produced a significantly greater reduction in pain intensity, greater pain relief, fewer withdrawals for inefficacy, greater percentage of patients who considered their medication effective, and greater percentage of patients considered by the investigator to have received drug-attributable benefits. In comparison with aspirin, 600 mg, meclofenamate sodium at either 200 mg or 100 mg produced significantly greater reduction in pain intensity and greater pain relief. The other measures of efficacy showed no significant differences between the two drugs. Side effects were minimal in all treatment groups. Meclofenamate sodium appears to be a safe and effective analgesic for the control of pain.     

Single doses of parecoxib sodium intravenously are as effective as ketorolac in reducing pain after oral surgery.

PURPOSE: Our goal was to compare the analgesic efficacy and safety of single doses of intravenous parecoxib sodium, a prodrug of the novel cyclooxygenase (COX)-2-selective inhibitor valdecoxib, with intravenous ketorolac and placebo in postoperative oral surgery patients. PATIENTS AND METHODS: Eligible patients experiencing moderate to severe pain within 6 hours of surgery to extract 2 or more impacted third molars were randomized to receive a single dose of parecoxib sodium 1, 2, 5, 10, 20, 50, or 100 mg; ketorolac 30 mg; or placebo. Analgesic efficacy was assessed over a 24-hour treatment period or until rescue analgesia was required. RESULTS: Parecoxib sodium doses (particularly 50 and 100 mg) had a rapid onset of analgesia (within 11 minutes). The analgesic efficacy of parecoxib sodium 20 to 100 mg was similar to that of ketorolac 30 mg. Parecoxib sodium doses below 20 mg had suboptimal analgesic activity compared with placebo and ketorolac. A plateau of efficacy was observed at the parecoxib sodium 50-mg dose. Parecoxib sodium 50 and 100 mg had a significantly longer duration of analgesia than ketorolac 30 mg. All doses of parecoxib sodium were well tolerated. CONCLUSIONS: Parecoxib sodium, a novel parenteral prodrug of the COX-2-selective inhibitor valdecoxib, is as effective and longer acting at 50- and 100-mg intravenous doses than a standard dose of ketorolac 30 mg intravenously. Parecoxib sodium appears to be safe and well tolerated and, therefore, merits further evaluation in other models of postsurgical pain.     

Paracetamol for pain relief after surgical removal of lower wisdom teeth.

Background: Paracetamol has been commonly used for the relief of postoperative pain following oral surgery. In this review we investigated the optimal dose of paracetamol and the optimal time for drug administration to provide pain relief, taking into account the side effects of different doses of the drug. This will inform dentists and their patients of the best strategy for pain relief after the surgical removal of wisdom teeth. Objectives: To assess the beneficial and harmful effects of paracetamol for pain relief after surgical removal of lower wisdom teeth, compared to placebo, at different doses and administered postoperatively. Search strategy: We searched the Cochrane Oral Health Group's Trials Register; the Cochrane Pain, Palliative and Supportive Care Group's Trials Register; CENTRAL; MEDLINE; EMBASE and the Current Controlled Trials Register. Handsearching included several dental journals. We checked the bibliographies of relevant clinical trials and review articles for studies outside the handsearched journals. We wrote to authors of the identified randomized controlled trials (RCTs), to manufacturers of analgesic pharmaceuticals, we searched personal references in an attempt to identify unpublished or ongoing RCTs. No language restriction was applied. The last electronic search was conducted on 24th August 2006. Selection criteria: Randomized, parallel group, placebo controlled, double blind clinical trials of paracetamol for acute pain, following third molar surgery. Data collection and analysis: All trials identified were scanned independently and in duplicate by two review authors, any disagreements were resolved by discussion, or if necessary a third review author was consulted. The proportion of patients with at least 50% pain relief was calculated for both paracetamol and placebo. The number of patients experiencing adverse events, and/or the total number of adverse events reported were analysed. Main results: Twenty-one trials met the inclusion criteria. A total of 2048 patients were initially enrolled in the trials (1148 received paracetamol, and 892 the placebo) and of these 1968 (96%) were included in the meta-analysis (1133 received paracetamol, and 835 the placebo). Paracetamol provided a statistically significant benefit when compared with placebo for pain relief and pain intensity at both 4 and 6 hours. Most studies were found to have moderate risk of bias, with poorly reported allocation concealment being the main problem. Risk ratio values for pain relief at 4 hours 2.85 (95% confidence interval (CI) 1.89 to 4.29), and at 6 hours 3.32 (95% CI 1.88 to 5.87). A statistically significant benefit was also found between up to 1000 mg and 1000 mg doses, the higher the dose giving greater benefit for each measure at both time points. There was no statistically significant difference between the number of patients who reported adverse events, overall this being 19% in the paracetamol group and 16% in the placebo group. Authors' conclusions: Paracetamol is a safe, effective drug for the treatment of postoperative pain following the surgical removal of lower wisdom teeth.     

Additive analgesic effects of oxycodone and ibuprofen in the oral surgery model.

PURPOSE: A traditional approach to achieve greater analgesic efficacy is to combine an efficacious dose of a nonopioid with a dose of an opioid sufficient to produce additive analgesia without a substantial increase in the incidence of adverse effects. This study evaluated the additive analagesic effects of the combination of ibuprofen and oxycodone. PATIENTS AND METHODS: A dose of 400 mg ibuprofen was compared with 400 mg ibuprofen with oxycodone in doses of 2.5, 5, or 10 mg in the oral surgery model of acute pain. Analgesic efficacy was measured with category and visual analog scales at 15, 30, 45, and 60 minutes and hourly up to 6 hours. RESULTS: Ibuprofen plus 10 mg oxycodone produced significantly greater analgesia compared with the other three groups, as measured by the visual analog scale from 15 minutes after drug administration up to the 2-hour observation. All four treatments were similar from 3 to 6 hours, with the area under the pain intensity difference curve being similar across groups. Neither the 2.5-mg nor the 5-mg oxycodone dose provided any additive analgesia over ibuprofen at any points. Addition of oxycodone resulted in a dose-related increase in the number of patients reporting adverse effects, with significantly greater drowsiness and vomiting at the 10-mg dose. CONCLUSIONS: These results indicate that additive analgesia can be achieved for the combination of a nonsteroidal anti-inflammatory drug and an orally effective opioid, with faster onset of relief for the combination of 400 mg ibuprofen and 10 mg oxycodone over the first 2 hours after administration, but at the expense of an increased incidence of adverse events.     

Comparison of presurgical and immediate postsurgical ibuprofen on postoperative periodontal pain.

Previous studies have indicated that non-steroidal anti-inflammatory drugs administered prior to oral surgery procedures are effective in reducing postoperative pain. The purpose of the present study was to compare the efficacy of medicating with ibuprofen immediately presurgically to medicating immediately postsurgically on postoperative pain associated with periodontal surgery. Sixty patients who were to undergo periodontal surgery were randomly divided into 3 groups: the I-pretreatment group received 600 mg ibuprofen immediately presurgically and placebo immediately after the surgery; the I-post-treatment group received placebo before surgery and 600 mg ibuprofen postsurgically; the placebo group received placebo at both time periods. Responses from an 8-hour pain diary completed by each subject were quantified and statistically evaluated non-parametrically. Results indicated that dosing with ibuprofen either immediately before or immediately after periodontal surgery significantly delays onset of pain as compared to placebo, with dosing after surgery demonstrating a significantly greater delay of onset of pain as compared to dosing presurgically. In addition, unlike the presurgical dosing, dosing postsurgically significantly decreases mean pain intensity for a combined 8-hour period following periodontal surgery as compared to placebo.     

Effects of sodium meclofenamate on postoperative pain following periodontal surgery.

The analgesic activity of single doses of meclofenamate (100 mg) was compared to aspirin (500 mg) and to placebo on 99 outpatients with moderate to severe pain following periodontal surgery under double-blind conditions. Pain intensity differences scores (PID) at the first, second, and third hour after the ingestion of the first capsule of each medication were used to determine the analgesic efficacy of the studied drugs. Kruskal Wallis test followed by the Mann-Whitney rank sum test were used in the statistical analysis of results. Meclofenamate was statistically superior to placebo and superior to aspirin in the second hour of evaluation, while aspirin was not superior to placebo during the 3-hour period of pain evaluation. It is concluded that meclofenamate is a non-steroidal antiinflammatory drug with interesting analgesic properties which can be used as directed as an alternative to aspirin or acetaminophen for the control of postoperative pain following periodontal surgery.