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1.  Topical analgesics for acute and chronic pain in adults 
This is the protocol for a review and there is no abstract. The objectives are as follows:
To provide an overview of the analgesic efficacy and associated adverse events of topical analgesics (primarily NSAIDs, rubefacients, capsaicin, lidocaine, and opioids) for the treatment of acute and chronic pain in adults.
doi:10.1002/14651858.CD008609
PMCID: PMC4234085  PMID: 25411557
2.  Rizatriptan for acute migraine headaches in adults 
This is the protocol for a review and there is no abstract. The objectives are as follows:
The objective of the review will be to determine the efficacy and tolerability of rizatriptan compared to placebo and other active interventions in the treatment of acute migraine headaches in adults.
doi:10.1002/14651858.CD008491
PMCID: PMC4233121  PMID: 25408622
3.  Intravenous parecoxib for acute postoperative pain in adults 
This is the protocol for a review and there is no abstract. The objectives are as follows:
To assess the efficacy and adverse effects of single dose parecoxib in studies of acute postoperative pain using methods that permit comparison with other analgesics evaluated in standardised trials using almost identical methods and outcomes.
doi:10.1002/14651858.CD004771.pub3
PMCID: PMC4176621  PMID: 25267899
4.  Single dose oral piroxicam for acute postoperative pain 
Background
This is an updated version of the original Cochrane review published in Issue 2, 2000. Piroxicam is a non-steroidal anti-inflammatory drug (NSAID) with analgesic properties, and is used mainly for treating rheumatic disorders. Some drugs have been directly compared against each other within a trial setting to determine their relative efficacies, whereas other have not. It is possible, however, to compare analgesics indirectly by examining the effectiveness of each drug against placebo when used in similar clinical situations.
Objectives
To determine the analgesic efficacy and adverse effects of single-dose piroxicam compared with placebo in moderate to severe postoperative pain. To compare the effects of piroxicam with other analgesics.
Search methods
Published studies were identified from systematic searching of MEDLINE, Biological Abstracts, EMBASE, CENTRAL and the Oxford Pain Relief Database in December 2007. Additional studies were identified from the reference lists of retrieved reports.
Selection criteria
The following inclusion criteria were used: full journal publication, randomised placebo controlled trial, double-blind design, adult participants, postoperative pain of moderate to severe intensity at the baseline assessment, postoperative administration of oral or intramuscular piroxicam.
Data collection and analysis
Summed pain intensity and pain relief data were extracted and converted into dichotomous information to yield the number of participants obtaining at least 50% pain relief. This was used to calculate estimates of relative benefit and number-needed-to-treat-to-benefit (NNT) for one participant to obtain at least 50% pain relief. Information was collected on adverse effects and estimates of relative risk and number-needed-to-treat-to-harm (NNH) were calculated.
Main results
In this update no further studies were found. The original search identified three studies (141 participants) which compared oral piroxicam 20 mg with placebo and one (15 participants) compared oral piroxicam 40 mg with placebo. For single doses of piroxicam 20 mg and 40 mg the respective NNT for at least 50% pain relief were 2.7 (2.1 to 3.8) [95% confidence interval (CI)] and 1.9 (1.2 to 4.3) [95% CI] compared with placebo over four to six hours in moderate to severe postoperative pain. The reported incidence of adverse effects was no higher with piroxicam (20 mg or 40 mg) than with placebo. No further additional studies were found in the updated search.
Authors’ conclusions
Piroxicam appears to be of similar efficacy to other NSAIDs and intramuscular morphine 10 mg when used as a single oral dose in the treatment of moderate to severe postoperative pain.
doi:10.1002/14651858.CD002762
PMCID: PMC4176623  PMID: 11034755
Acute Disease; Administration, Oral; Anti-Inflammatory Agents, Non-Steroidal [*administration & dosage; adverse effects]; Outcome Assessment (Health Care); Pain, Postoperative [*drug therapy]; Piroxicam [*administration & dosage; adverse effects]; Randomized Controlled Trials as Topic; Adult; Humans
5.  Single dose oral dihydrocodeine for acute postoperative pain 
Background
This is an updated version of the original Cochrane review published in Issue 2, 2000. Dihydrocodeine is a synthetic opioid analgesic developed in the early 1900s. Its structure and pharmacokinetics are similar to that of codeine and it is used for the treatment of postoperative pain or as an antitussive. It is becoming increasingly important to assess the relative efficacy and harm caused by different treatments. Relative efficacy can be determined when an analgesic is compared with control under similar clinical circumstances.
Objectives
To quantitatively assess the analgesic efficacy and adverse effects of single-dose dihydrocodeine compared with placebo in randomised trials in moderate to severe postoperative pain.
Search methods
Published reports were identified from electronic databases (MEDLINE, EMBASE, CENTRAL, the Oxford Pain Relief Database in December 2007, the original search was conducted in October 1999). Additional studies were identified from the reference lists of retrieved reports.
Selection criteria
Inclusion criteria: full journal publication, clinical trial, random allocation of participants to treatment groups, double blind design, adult participants, baseline pain of moderate to severe intensity, postoperative administration of study drugs, treatment arms which included dihydrocodeine and placebo and either oral or injected (intramuscular or intravenous) administration of study drugs.
Data collection and analysis
Data collection and analysis: summed pain intensity and pain relief data over four to six hours were extracted and converted into dichotomous information to yield the number of participants obtaining at least 50% pain relief. This was used to calculate relative benefit and number-needed-to-treat-to-benefit (NNT) for one participant to obtain at least 50% pain relief. Single-dose adverse effect data were collected and used to calculate relative risk and number-needed-to-treat-to-harm (NNH).
Main results
Fifty-two reports were identified in the original review as possible randomised trials which assessed dihydrocodeine in postoperative pain. Four reports met the inclusion criteria; all assessed oral dihydrocodeine. Three reports (194 participants) compared dihydrocodeine with placebo and one (120 participants) compared dihydrocodeine (30 mg or 60 mg) with ibuprofen 400 mg. For a single dose of dihydrocodeine 30 mg in moderate to severe postoperative pain the NNT for at least 50% pain relief was 8.1 (95% confidence interval 4.1 to 540) when compared with placebo over a period of four to six hours. Pooled data showed significantly more participants to have reported adverse effects with dihydrocodeine 30 mg than with placebo. When compared to ibuprofen 400 mg both dihydrocodeine 30 mg and 60 mg were significantly inferior. No additional studies were found for this update.
Authors’ conclusions
A single 30 mg dose of dihydrocodeine is not sufficient to provide adequate pain relief in postoperative pain. Statistical superiority of ibuprofen 400 mg over dihydrocodeine (30 mg or 60 mg) was shown. Since the last version of this review no new relevant studies have been identified.
doi:10.1002/14651858.CD002760
PMCID: PMC4176625  PMID: 11034754
Acute Disease; Analgesics, Non-Narcotic [administration & dosage]; Analgesics, Opioid [*administration & dosage]; Codeine [*administration & dosage; *analogs & derivatives]; Ibuprofen [administration & dosage]; Pain, Postoperative [*drug therapy]; Randomized Controlled Trials as Topic; Humans
6.  Eletriptan for acute migraine headaches in adults 
This is the protocol for a review and there is no abstract. The objectives are as follows:
The objective of the review will be to determine the efficacy and tolerability of eletriptan compared to placebo and other active interventions in the treatment of acute migraine headaches in adults.
doi:10.1002/14651858.CD008490
PMCID: PMC4176626  PMID: 25267910
7.  Zolmitriptan for acute migraine headaches in adults 
This is the protocol for a review and there is no abstract. The objectives are as follows:
The objective of the review will be to determine the efficacy and tolerability of zolmitriptan compared to placebo and other active interventions in the treatment of acute migraine headaches in adults.
doi:10.1002/14651858.CD008616
PMCID: PMC4176633  PMID: 25267904
8.  Single dose oral tenoxicam for acute postoperative pain in adults 
Background
Tenoxicam is a non-steroidal anti-inflammatory drug (NSAID) licensed for use in rheumatic disease and other musculoskeletal disorders in the UK, and is widely available in other countries worldwide. This review sought to evaluate the efficacy and safety of oral tenoxicam in acute postoperative pain, using clinical studies of patients with established pain, and with outcomes measured primarily over 6 hours using standard methods. This type of study has been used for many decades to establish that drugs have analgesic properties.
Objectives
To assess the efficacy of single dose oral tenoxicam in acute postoperative pain, and any associated adverse events.
Search methods
We searched The Cochrane Library (Issue 1, 2009), MEDLINE (March 2009); EMBASE via Ovid (March 2009); the Oxford Pain Relief Database.
Selection criteria
Randomised, double-blind, placebo-controlled clinical trials of oral tenoxicam for relief of acute postoperative pain in adults.
Data collection and analysis
Two review authors independently assessed trial quality and extracted data. The area under the “pain relief versus time” curve was used to derive the proportion of participants with tenoxicam experiencing least 50% pain relief over 4 to 6 hours, using validated equations. The number needed to treat to benefit (NNT) was calculated using 95% confidence intervals (CI). The proportion of participants using rescue analgesia over a specified time period, and time to use of rescue analgesia, were sought as additional measures of efficacy. Information on adverse events and withdrawals was also collected.
Main results
Not one of sixteen studies identified by the searches and examined in detail studied oral tenoxicam in patients with established postoperative pain and therefore no results are available.
Authors’ conclusions
In the absence of evidence of efficacy for oral tenoxicam in acute postoperative pain, its use in this indication is not justified at present. Because trials clearly demonstrating analgesic efficacy in the most basic of acute pain studies is lacking, use in other indications should be evaluated carefully. Given the large number of available drugs of this and similar classes which are effective, there is no urgent research agenda for this particular drug.
doi:10.1002/14651858.CD007591.pub2
PMCID: PMC4175441  PMID: 19588438
Acute Disease; Administration, Oral; Anti-Inflammatory Agents, Non-Steroidal [*administration & dosage]; Pain, Postoperative [*drug therapy]; Piroxicam [administration & dosage *analogs & derivatives]; Adult; Humans
9.  Single dose oral meloxicam for acute postoperative pain in adults 
Background
Meloxicam is a non-steroidal anti-inflammatory drug (NSAID) used mainly in treating pain associated with arthritis. The usual oral dose for osteoarthritis is 15 mg daily, but lower doses of 7.5 mg are advised in older patients. This review sought to evaluate the efficacy and safety of oral meloxicam in acute postoperative pain, using clinical studies of patients with established pain, and with outcomes measured primarily over 6 hours using standard methods. This type of study has been used for many decades to establish that drugs have analgesic properties.
Objectives
To assess the efficacy of single dose oral meloxicam in acute postoperative pain, and any associated adverse events.
Search methods
We searched Cochrane CENTRAL (Issue 2, 2009), MEDLINE (June 2009); EMBASE (June 2009); the Oxford Pain Relief Database.
Selection criteria
Randomised, double-blind, placebo-controlled clinical trials of oral meloxicam for relief of acute postoperative pain in adults.
Data collection and analysis
Two review authors independently assessed trial quality and extracted data. We planned to use area under the “pain relief versus time” curve to derive the proportion of participants with meloxicam experiencing least 50% pain relief over 4 to 6 hours, using validated equations; to use number needed to treat to benefit (NNT); the proportion of participants using rescue analgesia over a specified time period; time to use of rescue analgesia; information on adverse events and withdrawals.
Main results
No studies were identified by the searches that examined oral meloxicam in patients with established postoperative pain.
Authors’ conclusions
In the absence of evidence of efficacy, at present, for oral meloxicam in acute postoperative pain, its use in this indication is not justified. Because trials clearly demonstrating analgesic efficacy in the most basic of acute pain studies is lacking, use in other indications should be evaluated carefully. Given the large number of available drugs of this and similar classes, there is no urgent research agenda.
doi:10.1002/14651858.CD007552.pub2
PMCID: PMC4175538  PMID: 19821429
Acute Disease; Administration, Oral; Analgesics [*administration & dosage]; Cyclooxygenase Inhibitors [*administration & dosage]; Pain, Postoperative [*drug therapy]; Thiazines [*administration & dosage]; Thiazoles [*administration & dosage]; Adult; Humans
10.  Single dose oral fenbufen for acute postoperative pain in adults 
Background
Fenbufen is a non-selective non-steroidal anti-inflammatory drug (NSAID), used to treat acute and chronic painful conditions. There is no known systematic review of its use in acute postoperative pain.
Objectives
To assess efficacy, duration of action, and associated adverse events of single dose oral fenbufen in acute postoperative pain in adults.
Search methods
We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief database for studies to June 2009.
Selection criteria
Randomised, double blind, placebo-controlled trials of single dose orally administered fenbufen in adults with moderate to severe acute postoperative pain.
Data collection and analysis
Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk and number needed to treat to benefit (NNT) were calculated. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals were collected.
Main results
Searches identified only one study with (90 participants in total, 31 taking fenbufen). The study compared oral fenbufen 800 mg, fenbufen 400 mg, and placebo in participants with established postoperative pain. Fenbufen at both doses had apparent analgesic efficacy, but the numbers of participants was too small to allow sensible analysis. Gastrointestinal adverse events were noted in 4 of 15 participants taking fenbufen 800 mg.
Authors’ conclusions
In the absence of evidence of efficacy for oral fenbufen in acute postoperative pain, its use in this indication is not justified at present. Because trials clearly demonstrating analgesic efficacy in the most basic of acute pain studies is lacking, use in other indications should be evaluated carefully. Given the large number of available drugs of this and similar classes which are effective, there is no urgent research agenda for this particular drug.
doi:10.1002/14651858.CD007547.pub2
PMCID: PMC4175557  PMID: 19821427
Acute Disease; Administration, Oral; Analgesics [*administration & dosage]; Cyclooxygenase Inhibitors [*administration & dosage]; Pain, Postoperative [*drug therapy]; Phenylbutyrates [*administration & dosage]; Randomized Controlled Trials as Topic; Adult; Humans
11.  Single dose oral paracetamol (acetaminophen) with codeine for postoperative pain in adults 
Background
This is an updated version of the Cochrane review published in Issue 4, 1998. Combining drugs from different classes with different modes of action may offer opportunity to optimise efficacy and tolerability, using lower doses of each drug to achieve the same degree of pain relief. Previously we concluded that addition of codeine to paracetamol provided additional pain relief, but at expense of additional adverse events. New studies have been published since. This review sought to evaluate efficacy and safety of paracetamol plus codeine using current data, and compare findings with other analgesics evaluated similarly.
Objectives
Assess efficacy of single dose oral paracetamol plus codeine in acute postoperative pain, increase in efficacy due to the codeine component, and associated adverse events.
Search methods
We searched CENTRAL, MEDLINE, EMBASE, the Oxford Pain Relief Database in October 2008 for this update.
Selection criteria
Randomised, double-blind, placebo-controlled trials of paracetamol plus codeine, compared with placebo or the same dose of paracetamol alone, for relief of acute postoperative pain in adults.
Data collection and analysis
Two authors assessed trial quality and extracted data. The area under the “pain relief versus time” curve was used to derive proportion of participants with paracetamol plus codeine and placebo or paracetamol alone experiencing least 50% pain relief over four-to-six hours, using validated equations. Number-needed-to-treat-to-benefit (NNT) was calculated using 95% confidence intervals (CIs). Proportion of participants using rescue analgesia over a specified time period, and time to use of rescue analgesia, were sought as additional measures of efficacy. Information on adverse events and withdrawals were collected.
Main results
Twenty-six studies, with 2295 participants, were included comparing paracetamol plus codeine with placebo. Significant dose response was seen for the outcome of at least 50% pain relief over four-to-six hours, with NNTs of 2.2 (95% CI 1.8 to 2.9) for 800 to 1000 mg paracetamol plus 60 mg codeine, 3.9 (2.9 to 4.5) for 600 to 650 mg paracetamol plus 60 mg codeine, and 6.9 (4.8 to 12) for 300 mg paracetamol plus 30 mg codeine. Time to use of rescue medication was over four hours with paracetamol plus codeine and two hours with placebo. The NNT to prevent remedication was 5.6 (4.0 to 9.0) for 600 mg paracetamol plus 60 mg codeine over four to six hours. Adverse events increased of mainly mild to moderate severity with paracetamol plus codeine than placebo.
Fourteen studies, with 926 participants, were included in the comparison of paracetamol plus codeine with the same dose of paracetamol alone. Addition of codeine increased proportion of participants achieving at least 50% pain relief over four-to-six hours by 10 to 15%, increased time to use of rescue medication by about one hour, and reduced proportion of participants needing rescue medication by about 15% (NNT to prevent remedication 6.9 (4.2 to 19). Adverse events were mainly mild to moderate in severity and incidence did not differ between groups.
Authors’ conclusions
This update confirms previous findings that combining paracetamol with codeine provided clinically useful levels of pain relief in about 50% of patients with moderate to severe postoperative pain, compared with under 20% with placebo. New information for remedication shows that the combination extended the duration of analgesia by about one hour compared to treatment with the same dose of paracetamol alone. At higher doses, more participants experienced adequate pain relief, but the amount of information available for the 1000 mg paracetamol plus 60 mg codeine dose was small, and based on limited information.
doi:10.1002/14651858.CD001547.pub2
PMCID: PMC4171965  PMID: 19160199
Acetaminophen [*administration & dosage; adverse effects]; Administration, Oral; Analgesics, Non-Narcotic [*administration & dosage; adverse effects]; Analgesics, Opioid [*administration & dosage; adverse effects]; Codeine [*administration & dosage]; Drug Therapy, Combination; Pain, Postoperative [*drug therapy]; Adult; Humans
12.  Single dose oral ibuprofen for acute postoperative pain in adults 
Background
This review updates a 1999 Cochrane review showing that ibuprofen at various doses was effective in postoperative pain in single dose studies designed to demonstrate analgesic efficacy. New studies have since been published. Ibuprofen is one of the most widely used non-steroidal anti-inflammatory (NSAID) analgesics both by prescription and as an over-the-counter medicine. Ibuprofen is used for acute and chronic painful conditions.
Objectives
To assess analgesic efficacy of ibuprofen in single oral doses for moderate and severe postoperative pain in adults.
Search methods
We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to May 2009.
Selection criteria
Randomised, double blind, placebo-controlled trials of single dose orally administered ibuprofen (any formulation) in adults with moderate to severe acute postoperative pain.
Data collection and analysis
Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk and number-needed-to-treat-to-benefit (NNT) were calculated. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals were collected.
Main results
Seventy-two studies compared ibuprofen and placebo (9186 participants). Studies were predominantly of high reporting quality, and the bulk of the information concerned ibuprofen 200 mg and 400 mg. For at least 50% pain relief compared with placebo the NNT for ibuprofen 200 mg (2690 participants) was 2.7 (2.5 to 3.0) and for ibuprofen 400 mg (6475 participants) it was 2.5 (2.4 to 2.6). The proportion with at least 50% pain relief was 46% with 200 mg and 54% with 400 mg. Remedication within 6 hours was less frequent with higher doses, with 48% remedicating with 200 mg and 42% with 400 mg. The median time to remedication was 4.7 hours with 200 mg and 5.4 hours with 400 mg. Sensitivity analysis indicated that pain model and ibuprofen formulation may both affect the result, with dental impaction models and soluble ibuprofen salts producing better efficacy estimates. Adverse events were uncommon, and not different from placebo.
Authors’ conclusions
The very substantial amount of high quality evidence demonstrates that ibuprofen is an effective analgesic in treating postoperative pain. NNTs for 200 mg and 400 mg ibuprofen did not change significantly from the previous review even when a substantial amount of new information was added. New information is provided on remedication.
doi:10.1002/14651858.CD001548.pub2
PMCID: PMC4171980  PMID: 19588326
Administration, Oral; Analgesics, Non-Narcotic [* administration & dosage; adverse effects]; Ibuprofen [* administration & dosage; adverse effects]; Pain, Postoperative [* drug therapy]; Randomized Controlled Trials as Topic; Adult; Humans
13.  Vitamin D for the treatment of chronic painful conditions in adults 
Background
Vitamin D is produced in the skin after sun-light exposure and can also be obtained through food. Vitamin D deficiency has recently been linked with a range of diseases including chronic pain. Observational and circumstantial evidence suggests that there may be a role for vitamin D deficiency in the aetiology of chronic pain conditions.
Objectives
To assess the efficacy and adverse events of vitamin D supplementation in chronic painful conditions.
Search methods
We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to September 2009. This was supplemented by searching the reference lists of retrieved articles, textbooks and reviews.
Selection criteria
Studies were included if they were randomised double blind trials of vitamin D supplementation compared with placebo or with active comparators for the treatment of chronic pain conditions in adults.
Data collection and analysis
Two review authors independently selected the studies for inclusion, assessed methodological quality, and extracted data. Pooled analysis was not undertaken due to paucity and heterogeneity of data.
Main results
Four studies, with a total of 294 participants, were included. The studies were heterogeneous with regard to study quality, the chronic painful conditions that were investigated, and the outcome measures reported. Only one study reported a beneficial effect, the others found no benefit of vitamin D over placebo in treating chronic pain.
Authors’ conclusions
The evidence base for the use of vitamin D for chronic pain in adults is poor at present. This is due to low quality and insufficient randomised controlled trials in this area of research.
doi:10.1002/14651858.CD007771.pub2
PMCID: PMC4170888  PMID: 20091647
Arthritis, Rheumatoid [drug therapy]; Chronic Disease; Ergocalciferols [adverse effects; therapeutic use]; Hydroxycholecalciferols [adverse effects; therapeutic use]; Pain [*drug therapy; etiology]; Randomized Controlled Trials as Topic; Vitamin D [adverse effects; *therapeutic use]; Vitamin D Deficiency [complications; drug therapy]; Vitamins [adverse effects; *therapeutic use]; Adult; Humans
14.  Single dose oral aceclofenac for postoperative pain in adults 
Background
Aceclofenac is the prodrug of the non-steroidal anti-inflammatory drug (NSAID) diclofenac, widely used to treat acute and chronic pain. There are no known systematic reviews of its analgesic efficacy in acute postoperative pain. This review sought to evaluate the efficacy and safety of oral aceclofenac in acute postoperative pain, using clinical studies of patients with established pain, and with outcomes measured primarily over 6 hours using standard methods. This type of study has been used for many decades to establish that drugs have analgesic properties.
Objectives
To assess the efficacy of single dose oral aceclofenac in acute postoperative pain, and any associated adverse events.
Search methods
We searched The Cochrane Library (Issue 1, 2009), MEDLINE via Ovid (1966 to March 2009); EMBASE via Ovid (1980 to March 2009); the Oxford Pain Relief Database (1950 to 1994); and reference lists of articles.
Selection criteria
Randomised, double-blind, placebo-controlled clinical trials of oral aceclofenac for relief of acute postoperative pain in adults.
Data collection and analysis
Two review authors independently assessed trial quality and extracted data. The area under the “pain relief versus time” curve was used to derive the proportion of participants with paracetamol plus codeine and placebo or paracetamol alone experiencing least 50% pain relief over 4 to 6 hours, using validated equations. The number needed to treat to benefit (NNT) was calculated using 95% confidence intervals (CI). The proportion of participants using rescue analgesia over a specified time period, and time to use of rescue analgesia, were sought as additional measures of efficacy. Information on adverse events and withdrawals was also collected.
Main results
Searches identified only one study (217 participants total), which used oral aceclofenac 150 mg in patients with established postoperative pain. Aceclofenac 150 mg could not be distinguished from placebo, though ibuprofen 400 mg was distinguished from placebo.
Authors’ conclusions
In the absence of evidence of efficacy for oral aceclofenac in acute postoperative pain (at least at 150 mg single dose), its use in this indication is not justified. Because trials clearly demonstrating analgesic efficacy in the most basic of acute pain studies are lacking, use in other indications should be evaluated carefully. Given the large number of effective drugs available in this and similar classes of analgesics, there is no urgent research agenda required to demonstrate the effective dose of aceclofenac in acute postoperative pain.
doi:10.1002/14651858.CD007588.pub2
PMCID: PMC4170891  PMID: 19588436
Acute Disease; Administration, Oral; Anti-Inflammatory Agents, Non-Steroidal [*administration & dosage]; Diclofenac [administration & dosage; *analogs & derivatives]; Pain, Postoperative [*drug therapy]; Adult; Humans
15.  Single dose oral dexibuprofen [S(+)-ibuprofen] for acute postoperative pain in adults 
Background
Dexibuprofen (S(+)-ibuprofen) is a non-steroidal anti-inflammatory drug (NSAID) licensed for use in rheumatic disease and other musculoskeletal disorders in the UK, and widely available in other countries worldwide. It is an active isomer of ibuprofen. This review sought to evaluate the efficacy and safety of oral dexibuprofen in acute postoperative pain, using clinical studies of patients with established pain, and with outcomes measured primarily over 6 hours using standard methods. This type of study has been used for many decades to establish that drugs have analgesic properties.
Objectives
To assess efficacy, duration of action, and associated adverse events of single dose oral dexibuprofen in acute postoperative pain in adults.
Search methods
We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to May 2009.
Selection criteria
Randomised, double blind, placebo-controlled clinical trials of oral dexibuprofen for relief of acute postoperative pain in adults.
Data collection and analysis
Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk and number needed to treat to benefit (NNT) were calculated. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals were collected.
Main results
In the single included study, both S(+)-ibuprofen (dexibuprofen, an active isomer of ibuprofen) 200 mg and 400 mg gave high levels of response, with 31/51 (61%) and 35/50 (70%) respectively having at least 50% pain relief over 4 to 6 hours, compared with 2/25 (8%) with placebo. The median time to additional analgesic use was 5.8 hours, 6.1 hours, and 1.8 hours respectively. The numbers of participants was too small to calculate NNTs with any meaning.
Authors’ conclusions
The information from the single trial in acute postoperative pain suggests it to be a useful analgesic, but at doses not very different from racemic ibuprofen.
doi:10.1002/14651858.CD007550.pub2
PMCID: PMC4170892  PMID: 19588434
Acute Disease; Administration, Oral; Analgesics, Non-Narcotic [*administration & dosage]; Anti-Inflammatory Agents, Non-Steroidal [*administration & dosage]; Ibuprofen [administration & dosage; *analogs & derivatives]; Pain, Postoperative [*drug therapy]; Adult; Humans
16.  Single dose oral sulindac for acute postoperative pain in adults 
Background
Sulindac is a non-steroidal anti-inflammatory drug (NSAID) licensed for use in rheumatic disease and other musculoskeletal disorders in the UK, and widely available in other countries worldwide. This review sought to evaluate the efficacy and safety of oral sulindac in acute postoperative pain, using clinical studies of patients with established pain, and with outcomes measured primarily over 6 hours using standard methods. This type of study has been used for many decades to establish that drugs have analgesic properties.
Objectives
To assess the efficacy of single dose oral sulindac in acute postoperative pain, and any associated adverse events.
Search methods
We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies up to June 2009.
Selection criteria
Randomised, double-blind, placebo-controlled clinical trials of oral sulindac for relief of acute postoperative pain in adults.
Data collection and analysis
Two review authors independently assessed trial quality and extracted data. We planned to use area under the “pain relief versus time” curve to derive the proportion of participants with meloxicam experiencing least 50% pain relief over 4 to 6 hours, using validated equations; to use number needed to treat to benefit (NNT); the proportion of participants using rescue analgesia over a specified time period; time to use of rescue analgesia; information on adverse events and withdrawals.
Main results
No studies were identified by the searches that examined oral sulindac in patients with established postoperative pain.
Authors’ conclusions
In the absence of evidence of efficacy, at present, for oral sulindac in acute postoperative pain, its use in this indication is not justified. Because trials clearly demonstrating analgesic efficacy in the most basic of acute pain studies is lacking, use in other indications should be evaluated carefully. Given the large number of available drugs of this and similar classes, there is no urgent research agenda.
doi:10.1002/14651858.CD007540.pub2
PMCID: PMC4170893  PMID: 19821425
Acute Disease; Administration, Oral; Analgesics [* administration & dosage]; Cyclooxygenase Inhibitors [* administration & dosage]; Pain, Postoperative [* drug therapy]; Sulindac [* administration & dosage]; Adult; Humans
17.  Single dose oral nabumetone for acute postoperative pain in adults 
Background
Nabumetone is a non-steroidal anti-inflammatory drug (NSAID) used mainly in treating pain associated with arthritis. The usual oral dose for osteoarthritis is 1000 mg daily, and higher doses are not advised in older patients. There are no known systematic reviews of its analgesic efficacy in acute postoperative pain. This review sought to evaluate the efficacy and safety of oral nabumetone in acute postoperative pain, using clinical studies of patients with established pain, and with outcomes measured primarily over 6 hours using standard methods. This type of study has been used for many decades to establish whether drugs have analgesic properties.
Objectives
To assess the efficacy of single dose oral nabumetone in acute postoperative pain, and any associated adverse events.
Search methods
We searched The Cochrane Library (Issue 2, 2009), MEDLINE (May 2009); EMBASE via Ovid (May 2009); and the Oxford Pain Relief Database.
Selection criteria
Randomised, double-blind, placebo-controlled clinical trials of oral nabumetone for relief of acute postoperative pain in adults.
Data collection and analysis
Two review authors independently assessed trial quality and extracted data. The area under the “pain relief versus time” curve was used to derive the proportion of participants with nabumetone and placebo experiencing at least 50% pain relief over 4 to 6 hours, using validated equations. The number needed to treat to benefit (NNT) was calculated using 95% confidence intervals (CI). The proportion of participants using rescue analgesia over a specified time period, and time to use of rescue analgesia, were sought as additional measures of efficacy. Information on adverse events and withdrawals was also collected.
Main results
No studies were identified by the searches that examined oral nabumetone in participants with established postoperative pain.
Authors’ conclusions
In the absence of evidence of efficacy, at present, for oral nabumetone in acute postoperative pain, its use in this indication is not justified. Because trials clearly demonstrating analgesic efficacy in the most basic of acute pain studies is lacking, use in other indications should be evaluated carefully. Given the large number of available drugs of this and similar classes, there is no urgent research agenda.
doi:10.1002/14651858.CD007548.pub2
PMCID: PMC4170900  PMID: 19821428
Acute Disease; Administration, Oral; Analgesics [*administration & dosage]; Butanones [*administration & dosage]; Cyclooxygenase 2 Inhibitors [*administration & dosage]; Pain, Postoperative [*drug therapy]; Adult; Humans
18.  Single dose oral oxycodone and oxycodone plus paracetamol (acetaminophen) for acute postoperative pain in adults 
Background
Oxycodone is a strong opioid agonist used to treat severe pain. It is commonly combined with milder analgesics such as paracetamol. This review updates a previous review that concluded, based on limited data, that all doses of oxycodone exceeding 5 mg, with or without paracetamol, provided analgesia in postoperative pain, but with increased incidence of adverse events compared with placebo. Additional new studies provide more reliable estimates of efficacy and harm.
Objectives
To assess efficacy, duration of action, and associated adverse events of single dose oral oxycodone, with or without paracetamol, in acute postoperative pain in adults.
Search methods
Cochrane CENTRAL, MEDLINE, EMBASE and Oxford Pain Relief Database, searched in May 2009.
Selection criteria
Randomised, double blind, placebo-controlled trials of single dose orally administered oxycodone, with or without paracetamol, in adults with moderate to severe acute postoperative pain.
Data collection and analysis
Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk and number-needed-to-treat-to-benefit (NNT) were calculated. Numbers of participants remedicating over specified time periods, and time-to-use of rescue medication, were sought as additional measures of efficacy. Adverse events and withdrawals information was collected.
Main results
This updated review includes 20 studies, with 2641 participants. For oxycodone 15 mg alone compared with placebo, the NNT for at least 50% pain relief was 4.6 (95% Confidence Interval 2.9 to 11). For oxycodone 10 mg plus paracetamol 650 mg, the NNT was 2.7 (2.4 to 3.1). A dose response was demonstrated for this outcome with combination therapy. Duration of effect was 10 hours with oxycodone 10 mg plus paracetamol 650 mg, and 4 hours with half that dose. Fewer participants needed rescue medication over 6 hours at the higher dose. Adverse events occurred more frequently with combination therapy than placebo, but were generally described as mild to moderate in severity and rarely led to withdrawal.
Authors’ conclusions
Single dose oxycodone is an effective analgesic in acute postoperative pain at doses over 5 mg; oxycodone is two to three times stronger than codeine. Efficacy increases when combined with paracetamol. Oxycodone 10 mg plus paracetamol 650 mg provides good analgesia to half of those treated, comparable to commonly used non-steroidal anti-inflammatory drugs, with the benefit of longer duration of action.
doi:10.1002/14651858.CD002763.pub2
PMCID: PMC4170904  PMID: 19588335
Acetaminophen [*administration & dosage; adverse effects]; Acute Disease; Analgesics, Non-Narcotic [*administration & dosage; adverse effects]; Analgesics, Opioid [*administration & dosage; adverse effects]; Drug Synergism; Drug Therapy, Combination; Oxycodone [*administration & dosage; adverse effects]; Pain, Postoperative [*drug therapy]; Randomized Controlled Trials as Topic; Adult; Humans
19.  Single dose oral nefopam for acute postoperative pain in adults 
Background
Nefopam is a centrally-acting but non-opioid analgesic drug of the benzoxazocine chemical class, developed in the early 1970s. It is widely used, mainly in European countries, for the relief of moderate to severe pain as an alternative to opioid analgesic drugs, and used in rheumatic disease and other musculoskeletal disorders in the UK. This review sought to evaluate the efficacy and safety of oral nefopam in acute postoperative pain, using clinical studies of patients with established pain, and with outcomes measured primarily over 6 hours using standard methods. This type of study has been used for many decades to establish that drugs have analgesic properties.
Objectives
To assess the efficacy of single dose oral nefopam in acute postoperative pain, and any associated adverse events.
Search methods
We searched CENTRAL (Issue 2, 2009), MEDLINE (1966 to May 2009); EMBASE via Ovid (1980 to May 2009); the Oxford Pain Relief Database (1950 to 1994); and reference lists of studies found.
Selection criteria
Randomised, double-blind, placebo-controlled clinical trials of oral nefopam for relief of acute postoperative pain in adults.
Data collection and analysis
Two review authors independently assessed trial quality and extracted data. The area under the “pain relief versus time” curve was used to derive the proportion of participants with nefopam and placebo experiencing least 50% pain relief over 4 to 6 hours, using validated equations. The number-needed-to-treat-to-benefit (NNT) was calculated using 95% confidence intervals (CIs). The proportion of participants using rescue analgesia over a specified time period, and time to use of rescue analgesia, were sought as additional measures of efficacy. Information on adverse events and withdrawals was also collected.
Main results
No included studies were identified after examining in detail thirteen studies on oral nefopam in participants with established postoperative pain.
Authors’ conclusions
In the absence of evidence of efficacy for oral nefopam in acute postoperative pain, its use in this indication is not justified. Because trials clearly demonstrating analgesic efficacy in the most basic of acute pain studies are lacking, use in other indications should be evaluated carefully. Given the large number of available drugs of this and similar classes, there is no urgent research agenda.
doi:10.1002/14651858.CD007442.pub2
PMCID: PMC4170989  PMID: 19588431
Acute Disease; Administration, Oral; Analgesics, Non-Narcotic [* administration & dosage]; Nefopam [* administration & dosage]; Pain, Postoperative [* drug therapy]; Adult; Humans
20.  Single dose oral acemetacin for acute postoperative pain in adults 
Background
Acemetacin is a non-steroidal anti-inflammatory drug (NSAID) licensed for use in rheumatic disease and other musculoskeletal disorders in the UK, and widely available in other countries worldwide. This review sought to evaluate the efficacy and safety of oral acemetacin in acute postoperative pain, using clinical studies of patients with established pain, and with outcomes measured primarily over 6 hours using standard methods. This type of study has been used for many decades to establish that drugs have analgesic properties.
Objectives
To assess the efficacy of single dose oral acemetacin in acute postoperative pain, and any associated adverse events.
Search methods
We searched CENTRAL (Issue 2, 2009), MEDLINE via Ovid (1966 to May 2009); EMBASE via Ovid (1980 to May 2009); the Oxford Pain Relief Database (1950 to 1994); and reference lists of articles.
Selection criteria
Randomised, double-blind, placebo-controlled clinical trials of oral acemetacin for relief of acute postoperative pain in adults.
Data collection and analysis
Two review authors independently assessed trial quality and extracted data. The area under the “pain relief versus time” curve was used to derive the proportion of participants with acemetacin and placebo experiencing least 50% pain relief over 4 to 6 hours, using validated equations. The number needed to treat to benefit (NNT) was calculated using 95% confidence intervals. The proportion of participants using rescue analgesia over a specified time period, and time to use of rescue analgesia, were sought as additional measures of efficacy. Information on adverse events and withdrawals was also collected.
Main results
No study fulfilled the inclusion criteria.
Authors’ conclusions
In the absence of randomised evidence of efficacy for oral acemetacin in acute postoperative pain, we cannot, at present, make any conclusions regarding its effectiveness. Because trials clearly demonstrating analgesic efficacy in the most basic of acute pain studies is lacking, use in other indications should be evaluated carefully. Given the large number of available drugs of this kind and similar classes, there is no urgent research agenda for this drug.
doi:10.1002/14651858.CD007589.pub2
PMCID: PMC4170991  PMID: 19588437
Acute Disease; Administration, Oral; Anti-Inflammatory Agents, Non-Steroidal [*administration & dosage]; Indomethacin [administration & dosage; * analogs & derivatives]; Pain, Postoperative [* drug therapy]; Adult; Humans
21.  Single dose oral tiaprofenic acid for acute postoperative pain in adults 
Background
Tiaprofenic acid is a a non-steroidal anti-inflammatory drug (NSAID). It is widely available around the world, with indications for osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, periarticular disorders, and strains and sprains. This review sought to evaluate the efficacy and safety of oral tiaprofenic acid in acute postoperative pain, using clinical studies of patients with established pain, and with outcomes measured primarily over 6 hours using standard methods. This type of study has been used for many decades to establish that drugs have analgesic properties.
Objectives
To assess the efficacy of single dose oral tiaprofenic acid in acute postoperative pain, and any associated adverse events.
Search methods
We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to June 2009.
Selection criteria
Randomised, double blind, placebo-controlled trials of single dose orally administered tiaprofenic acid in adults with moderate to severe acute postoperative pain.
Data collection and analysis
Two review authors independently assessed trial quality and extracted data. We planned to use area under the “pain relief versus time” curve to derive the proportion of participants with tiaprofenic acid experiencing at least 50% pain relief over 4 to 6 hours, using validated equations; to use number needed to treat to benefit (NNT); the proportion of participants using rescue analgesia over a specified time period; time to use of rescue analgesia; information on adverse events and withdrawals.
Main results
Not one of eleven studies identified by the searches and examined in detail studied oral tiaprofenic acid against placebo in patients with established postoperative pain and therefore no results are available.
Authors’ conclusions
In the absence of evidence of efficacy for oral tiaprofenic acid in acute postoperative pain, its use in this indication is not justified at present. Because trials clearly demonstrating analgesic efficacy in the most basic of acute pain studies is lacking, use in other indications should be evaluated carefully. Given the large number of available drugs of this and similar classes which are effective, there is no urgent research agenda for this particular drug.
doi:10.1002/14651858.CD007542.pub2
PMCID: PMC4170996  PMID: 19821426
Acute Disease; Administration, Oral; Analgesics [*administration & dosage]; Anti-Inflammatory Agents, Non-Steroidal [*administration & dosage]; Pain, Postoperative [*drug therapy]; Propionates [*administration & dosage]; Adult; Humans
22.  Single dose oral mefenamic acid for acute postoperative pain in adults 
Background
Mefenamic acid is a non-steroidal anti-inflammatory drug (NSAID). It is most often used for treating pain of dysmenorrhoea in the short term (seven days or less), as well as mild to moderate pain including headache, dental pain, postoperative and postpartum pain. It is widely available in many countries worldwide.
Objectives
To assess the efficacy of single dose oral mefenamic acid in acute postoperative pain, and any associated adverse events.
Search methods
We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to December 2010.
Selection criteria
Single oral dose, randomised, double-blind, placebo-controlled trials of mefenamic acid for relief of established moderate to severe postoperative pain in adults.
Data collection and analysis
Studies were assessed for methodological quality and the data extracted by two review authors independently. Summed total pain relief (TOTPAR) or pain intensity difference (SPID) over 4 to 6 hours was used to calculate the number of participants achieving at least 50% pain relief. These derived results were used to calculate, with 95% confidence intervals, the relative benefit compared to placebo, and the number needed to treat (NNT) for one participant to experience at least 50% pain relief over 4 to 6 hours. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals was collected.
Main results
Four studies with 842 participants met the inclusion criteria; 126 participants were treated with mefenamic acid 500 mg, 67 with mefenamic acid 250 mg, 197 with placebo, and 452 with lignocaine, aspirin, zomepirac or nimesulide. Participants had pain following third molar extraction, episiotomy and orthopaedic surgery. The NNT for at least 50% pain relief over 6 hours with a single dose of mefenamic acid 500 mg compared to placebo was 4.0 (2.7 to 7.1), and the NNT to prevent use of rescue medication over 6 hours was 6.5 (3.6 to 29). There were insufficient data to analyse other doses or active comparators, or numbers of participants experiencing any adverse events. No serious adverse events or adverse event withdrawals were reported in these studies.
Authors’ conclusions
Oral mefenamic acid 500 mg was effective at treating moderate to severe acute postoperative pain, based on limited data. Efficacy of other doses, and safety and tolerability could not be assessed.
doi:10.1002/14651858.CD007553.pub2
PMCID: PMC4170999  PMID: 21412904
Acute Disease; Administration, Oral; Anti-Inflammatory Agents, Non-Steroidal [*administration & dosage; therapeutic use]; Aspirin [administration & dosage; therapeutic use]; Mefenamic Acid [*administration & dosage; therapeutic use]; Pain, Postoperative [*drug therapy]; Randomized Controlled Trials as Topic; Sulfonamides [administration & dosage; therapeutic use]; Tolmetin [administration & dosage; analogs & derivatives; therapeutic use]; Adult; Humans
23.  Gabapentin for chronic neuropathic pain and fibromyalgia in adults 
Background
This review updates parts of two earlier Cochrane reviews investigating effects of gabapentin in chronic neuropathic pain (pain due to nerve damage). Antiepileptic drugs are used to manage pain, predominantly for chronic neuropathic pain, especially when the pain is lancinating or burning.
Objectives
To evaluate the analgesic effectiveness and adverse effects of gabapentin for chronic neuropathic pain management.
Search methods
We identified randomised trials of gabapentin in acute, chronic or cancer pain from MEDLINE, EMBASE, and CENTRAL. We obtained clinical trial reports and synopses of published and unpublished studies from Internet sources. The date of the most recent search was January 2011.
Selection criteria
Randomised, double-blind studies reporting the analgesic and adverse effects of gabapentin in neuropathic pain with assessment of pain intensity and/or pain relief, using validated scales. Participants were adults aged 18 and over.
Data collection and analysis
Two review authors independently extracted data. We calculated numbers needed to treat to benefit (NNTs), concentrating on IMM-PACT (Initiative on Methods, Measurement and Pain Assessment in Clinical Trials) definitions of at least moderate and substantial benefit, and to harm (NNH) for adverse effects and withdrawal. Meta-analysis was undertaken using a fixed-effect model.
Main results
Twenty-nine studies (3571 participants), studied gabapentin at daily doses of 1200 mg or more in 12 chronic pain conditions; 78% of participants were in studies of postherpetic neuralgia, painful diabetic neuropathy or mixed neuropathic pain. Using the IMMPACT definition of at least moderate benefit, gabapentin was superior to placebo in 14 studies with 2831 participants, 43% improving with gabapentin and 26% with placebo; the NNT was 5.8 (4.8 to 7.2). Using the IMMPACT definition of substantial benefit, gabapentin was superior to placebo in 13 studies with 2627 participants, 31% improving with gabapentin and 17% with placebo; the NNT was 6.8 (5.6 to 8.7). These estimates of efficacy are more conservative than those reported in a previous review. Data from few studies and participants were available for other painful conditions.
Adverse events occurred significantly more often with gabapentin. Persons taking gabapentin can expect to have at least one adverse event (66%), withdraw because of an adverse event (12%), suffer dizziness (21%), somnolence (16%), peripheral oedema (8%), and gait disturbance (9%). Serious adverse events (4%) were no more common than with placebo.
There were insufficient data for comparisons with other active treatments.
Authors’ conclusions
Gabapentin provides pain relief of a high level in about a third of people who take if for painful neuropathic pain. Adverse events are frequent, but mostly tolerable. More conservative estimates of efficacy resulted from using better definitions of efficacy outcome at higher, clinically important, levels, combined with a considerable increase in the numbers of studies and participants available for analysis.
doi:10.1002/14651858.CD007938.pub2
PMCID: PMC4171034  PMID: 21412914
Amines [adverse effects; *therapeutic use]; Analgesics [adverse effects; *therapeutic use]; Chronic Disease; Cyclohexanecarboxylic Acids [adverse effects; *therapeutic use]; Fibromyalgia [*drug therapy]; Neuralgia [*drug therapy]; Randomized Controlled Trials as Topic; gamma-Aminobutyric Acid [adverse effects; *therapeutic use]; Humans
24.  Single dose oral indometacin for the treatment of acute postoperative pain 
Background
This is an updated version of the original Cochrane review published in Issue 4, 2004. Indometacin is a non-steroidal anti-inflammatory drug (NSAID) used most commonly for the treatment of inflammation and pain resulting from rheumatic disease (arthritis), and less commonly in postoperative pain management. When taken for chronic pain conditions, indometacin has been associated with a high incidence of adverse events. The benefits and harms of orally-administered indometacin for postoperative pain are not clear.
Objectives
To determine the efficacy of a single dose of oral indometacin compared with placebo in treating acute postoperative pain in adults, and to analyse information relating to adverse events.
Search methods
We searched the Cochrane CENTRAL Register of Controlled Trials in The Cochrane Library, MEDLINE, EMBASE and the Oxford Pain Relief Database for relevant studies in January 2002 and for the updated search in December 2007. Additional studies were sought from the reference lists of retrieved studies.
Selection criteria
Studies were included in the review if they were randomised, double blind, placebo-controlled clinical trials using a single oral dose of indometacin in adults with acute postoperative pain.
Data collection and analysis
Studies were assessed independently by two review authors. Pain relief or pain intensity data were extracted and converted into dichotomous information to give the number of participants with at least 50% pain relief over four to six hours. The relative benefit for at least 50% pain relief was calculated.
Main results
In the original review one study of 59 women with post-episiotomy pain met the inclusion criteria. The dose of indometacin assessed against placebo was 50 mg, and the results concluded that indometacin was not significantly better than placebo for relieving postoperative pain at four to six hours. There was insufficient information to conduct further efficacy analyses or assess adverse events. No further studies were identified in the update of this review.
Authors’ conclusions
Conclusions about the clinical efficacy of indometacin for postoperative pain cannot be made unless more studies are conducted for a variety of surgical procedures, and different doses of indometacin are assessed. Since the last version of this review no new relevant studies have been identified.
doi:10.1002/14651858.CD004308.pub2
PMCID: PMC4171122  PMID: 15495100
Administration, Oral; Anti-Inflammatory Agents, Non-Steroidal [*administration & dosage]; Episiotomy; Indomethacin [*administration & dosage]; Pain, Postoperative [*drug therapy]; Female; Humans
25.  Single dose oral ketoprofen and dexketoprofen for acute postoperative pain in adults 
Background
Ketoprofen is a non-selective non-steroidal anti-inflammatory drug (NSAID) used to treat acute and chronic painful conditions. Dexketoprofen is the (S)-enantiomer, which is believed to confer analgesia. Theoretically dexketoprofen is expected to provide equivalent analgesia to ketoprofen at half the dose, with a consequent reduction in gastrointestinal adverse events.
Objectives
To assess efficacy, duration of action, and associated adverse events of single dose oral ketoprofen and dexketoprofen in acute postoperative pain in adults.
Search methods
We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to August 2009.
Selection criteria
Randomised, double blind, placebo-controlled trials of single dose orally administered ketoprofen and dexketoprofen in adults with moderate to severe acute postoperative pain.
Data collection and analysis
Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk and number-needed-to-treat-to-benefit (NNT) were calculated. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals was collected.
Main results
Fourteen studies compared ketoprofen (968 participants) at mainly 25 mg and 50 mg with placebo (520 participants). Seven studies compared dexketoprofen (681 participants) at mainly 10 mg to 25 mg with placebo (289 participants). Studies were of adequate reporting quality, and participants had pain following dental, orthopaedic, obstetric, gynaecological and general surgery. There was considerable clinical heterogeneity between studies in dental and other types of surgery, particularly bunionectomy, which limited analysis.
Ketoprofen at doses between 12.5 mg and 100 mg produced NNTs for at least 50% pain relief over 4 to 6 hours of 2.4 to 3.3. For dental studies only there was a trend to more efficacy at higher doses, with NNT decreasing from 2.4 at 12.5 mg to 1.6 at 100 mg. Dexketoprofen at doses of 10/12.5 mg and 20/25 mg produced NNTs for at least 50% pain relief over 4 to 6 hours of 3.2 and 3.6, with no obvious dose response. Significantly fewer participants used rescue medication with ketoprofen and dexketoprofen than placebo. The median time to remedication was about 5 hours with ketoprofen and 4 hours with dexketoprofen. The expected equivalent efficacy with a half dose of dexketoprofen compared to ketoprofen was not demonstrated.
Adverse events were uncommon with both drugs, and not significantly different from placebo.
Authors’ conclusions
Ketoprofen at doses of 25 mg to 100 mg is an effective analgesic in moderate to severe acute postoperative pain with an NNT for at least 50% pain relief of 3.3 with a 50 mg dose. This is similar to that of commonly used NSAIDs such as ibuprofen (NNT 2.5 for 400 mg dose) and diclofenac (NNT 2.7 at 50 mg dose). Duration of action is about 5 hours. Dexketoprofen is also effective with NNTs of 3.2 to 3.6 in the dose range 10 mg to 25 mg. Both drugs were well tolerated in single doses.
doi:10.1002/14651858.CD007355.pub2
PMCID: PMC4171124  PMID: 19821407
Acute Disease; Administration, Oral; Analgesics, Non-Narcotic [* administration & dosage]; Anti-Inflammatory Agents, Non-Steroidal [* administration & dosage]; Ketoprofen [* administration & dosage; * analogs & derivatives]; Pain, Postoperative [* drug therapy]; Stereoisomerism; Adult; Humans

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