Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009 Jul 8;2009(3):CD007442.
doi: 10.1002/14651858.CD007442.pub2.

Single dose oral nefopam for acute postoperative pain in adults

Affiliations

Single dose oral nefopam for acute postoperative pain in adults

Manish Kakkar et al. Cochrane Database Syst Rev. .

Abstract

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 strategy: 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.

PubMed Disclaimer

Conflict of interest statement

SD, RAM & HJM have received research support from charities, government and industry sources at various times. RAM and HJM have consulted for various pharmaceutical companies. RAM, and HJM have received lecture fees from pharmaceutical companies related to analgesics and other healthcare interventions. Support for this review came from Oxford Pain Research, the NHS Cochrane Collaboration Programme Grant Scheme, and NIHR Biomedical Research Centre Programme.

Update of

  • doi: 10.1002/14651858.CD007442

References

References to studies excluded from this review

Bloomfield 1980 {published data only}
    1. Bloomfield SS, Barden TP, Mitchell J. Nefopam and propoxyphene in episiotomy pain. Clinical Pharmacology and Therapeutics 1980;27(4):502‐7. [PUBMED: 7357809] - PubMed
Calmi 1985 {published data only}
    1. Calmi D, Pagnoni B, Tiengo M, Ravanelli A, Savio G, Dal Pra ML. Nefopam in postoperative pain. Arzneimittel‐Forschung 1985;35(6):981‐3. [PUBMED: 3927931] - PubMed
Campos 1980 {published data only}
    1. Campos VM, Solis EL. The analgesic and hypothermic effects of nefopam , morphine, aspirin, diphenhydramine ,and placebo. The Journal of Clinical Pharmacology 1980;20(1):42‐9. - PubMed
Du Manoir 2003 {published data only}
    1. Du Manoir B, Aubrun F, Langlois M, Guern ME, Alquier C, Chauvin M, et al. Randomized prospective study of the analgesic effect of nefopam after orthopaedic surgery. British Journal of Anaesthesia 2003;91(6):836‐41. [PUBMED: 14633755] - PubMed
Gassel 1976 {published data only}
    1. Gassel MM, Diamantopoulos E, Petropoulos V, Hughes AC, Ballesteros ML, Re ON. Controlled clinical trial of oral and parenteral nefopam hydrochloride. A novel and potent analgesic drug. Journal of Clinical Pharmacology 1976;16(1):34‐41. [PUBMED: 1107359] - PubMed
Goucke 1990 {published data only}
    1. Goucke CR, Keaveny JP, Kay B, Healy TE, Ryan M. The effect of diclofenac and nefopam on postoperative dental pain. Anaesthesia 1990;45(4):329‐31. [PUBMED: 2186651] - PubMed
Hedges 1978 {published data only}
    1. Hedges A, Wadsworth J, Turner P. A double‐blind comparison of nefopam and placebo in post‐operative pain. Current Medical Research and Opinion 1978;5(8):614‐7. [PUBMED: 361346] - PubMed
McLintock 1988 {published data only}
    1. McLintock TT, Kenny GN, Howie JC, McArdle CS, Lawrie S, Aitken H. Assessment of the analgesic efficacy of nefopam hydrochloride after upper abdominal surgery: a study using patient controlled analgesia. The British Journal of Surgery 1988;75(8):779‐81. [PUBMED: 3167526] - PubMed
Pandit 1989 {published data only}
    1. Pandit PN, Oke VG, Jha RJ, Bowalekar SK, Raghu CN. Double‐blind clinical trial of nefopam in comparison with pentazocine in surgical patients. The British Journal of Clinical Practice 1989;43(6):209‐14. [PUBMED: 2597600] - PubMed
Phillips 1979 {published data only}
    1. Phillips G, Vickers MD. Nefopam in postoperative pain. British Journal of Anaesthesia 1979;51(10):961‐5. [PUBMED: 391253] - PubMed
Sidhu 1993 {published data only}
    1. Sidhu BS, Khichy S, Singh KH. Comparative evaluation of intramuscular buprenorphine, pentazocine and nefopam in post‐operative pain relief. Journal of the Indian Medical Association 1993;91(11):288‐9. [PUBMED: 8138651] - PubMed
Tigerstedt 1977 {published data only}
    1. Tigerstedt I, Sipponen J, Tammisto T, Turunen M. Comparison of nefopam and pethidine in postoperative pain. British Journal of Anaesthesia 1977;49(11):1133‐8. [PUBMED: 337983] - PubMed
Tigerstedt 1979 {published data only}
    1. Tigerstedt I, Tammisto T, Leander P. Comparison of the analgesic dose‐effect relationships of nefopam and oxycodone in postoperative pain. Acta Anaesthesiologica Scandinavica 1979;23(6):555‐60. [PUBMED: 397711] - PubMed

Additional references

Barden 2004
    1. Barden J, Edwards JE, McQuay HJ, Wiffen PJ, Moore RA. Relative efficacy of oral analgesics after third molar extraction. British Dental Journal 2004;197(7):407‐11. - PubMed
Clarke 2009
    1. Rachel Clarke, Sheena Derry, R Andrew Moore, Henry J McQuay. Single dose oral etoricoxib for acute postoperative pain in adults. Cochrane Database of Systematic Reviews 2009, Issue 2. [DOI: 10.1002/14651858.CD004309.pub2] - DOI - PubMed
Collins 1997
    1. Collins SL, Moore RA, McQuay HJ. The visual analogue pain intensity scale: what is moderate pain in millimetres?. Pain 1997;72:95‐7. - PubMed
Collins 2001
    1. Collins SL, Edwards J, Moore RA, Smith LA, McQuay HJ. Seeking a simple measure of analgesia for mega‐trials: is a single global assessment good enough?. Pain 2001;91(1‐2):189‐94. - PubMed
Cook 1995
    1. Cook RJ, Sackett DL. The number needed to treat: a clinically useful measure of treatment effect. BMJ 1995;310(6977):452‐4. - PMC - PubMed
Cooper 1991
    1. Cooper SA. Single‐dose analgesic studies: the upside and downside of assay sensitivity. The Design of Analgesic Clinical Trials. Advances in Pain Research Therapy 1991;18:117‐24.
Derry 2008
    1. Derry S, Moore RA, McQuay HJ. Single dose oral celecoxib for acute postoperative pain. Cochrane Database of Systematic Reviews 2008, Issue 2. [DOI: 10.1002/14651858.CD004233] - DOI - PubMed
Derry C 2009a
    1. Derry C, Derry S, Moore RA, McQuay HJ. Single dose oral naproxen and naproxen sodium for acute postoperative pain in adults. Cochrane Database of Systematic Reviews 2009, Issue 1. [DOI: 10.1002/14651858.CD004234.pub2] - DOI - PMC - PubMed
Derry C 2009b
    1. Derry C, Derry S, Moore RA, McQuay HJ. Single dose oral ibuprofen for acute postoperative pain in adult. Cochrane Database of Systematic Reviews 2009, Issue 3. - PMC - PubMed
Derry P 2009
    1. Derry P, Derry S, Moore RA, McQuay HJ. Single dose oral diclofenac for acute postoperative pain in adults. Cochrane Database of Systematic Reviews 2009, Issue 2. [DOI: 10.1002/14651858.CD004768.pub2] - DOI - PMC - PubMed
Evans 2008
    1. Evans MS, Lysakowski C, Tramèr MR. Nefopam for the prevention of postoperative pain: quantitative systematic review. British Journal of Anaesthesia 2008;101(5):610‐7. [DOI: 10.1093/bja/aen267] - DOI - PubMed
Fletcher 2008
    1. Fletcher D, Fermanian C, Mardaye A, Aegerter P, Pain and Regional Anesthesia Committee of the French Anesthesia and Intensive Care Society. A patient‐based national survey on postoperative pain management in France reveals significant achievements and persistent challenges. Pain 2008;137(2):441‐51. [DOI: 10.1016/j.pain.2008.02.026] - DOI - PubMed
Heel 1980
    1. Heel RC, Brogden RN, Pakes GE, Speight TM, Avery GS. Nefopam: a review of its pharmacological properties and therapeutic efficacy. Drugs 1980;19(4):249‐67. - PubMed
Jadad 1996a
    1. Jadad AR, Carroll D, Moore RA, McQuay H. Developing a database of published reports of randomised clinical trials in pain research. Pain 1996;66(2‐3):239‐46. - PubMed
Jadad 1996b
    1. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJM, Gavaghan DJ, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary?. Controlled Clinical Trials 1996;17:1‐12. - PubMed
L'Abbe 1987
    1. L'Abbé KA, Detsky AS, O'Rourke K. Meta‐analysis in clinical research. Annals of Internal Medicine 1987;107:224‐33. - PubMed
Lloyd 2009
    1. Lloyd R, Derry S, Moore RA, McQuay HJ. Intravenous or intramuscular parecoxib for acute postoperative pain in adults. Cochrane Database of Systematic Reviews 2009, Issue 2. [DOI: 10.1002/14651858.CD004771.pub4] - DOI - PMC - PubMed
McQuay 2005
    1. McQuay HJ, Moore RA. Placebo. Postgraduate Medical Journal 2005;81:155‐60. - PMC - PubMed
Moher 1999
    1. Moher D, Cook DJ, Eastwood S, Olkin I, Rennie D, Stroup DF. Improving the quality of reports of meta‐analyses of randomised controlled trials: the QUOROM statement. Quality of Reporting of Meta‐analyses. Lancet 1999;354(9193):1896‐900. - PubMed
Moore 1996
    1. Moore A, McQuay H, Gavaghan D. Deriving dichotomous outcome measures from continuous data in randomised controlled trials of analgesics. Pain 1996;66(2‐3):229‐37. [DOI: 10.1016/0304-3959(96)03032-1] - DOI - PubMed
Moore 1997a
    1. Moore A, Moore O, McQuay H, Gavaghan D. Deriving dichotomous outcome measures from continuous data in randomised controlled trials of analgesics: use of pain intensity and visual analogue scales. Pain 1997;69(3):311‐5. [DOI: 10.1016/S0304-3959(96)03306-4] - DOI - PubMed
Moore 1997b
    1. Moore A, McQuay H, Gavaghan D. Deriving dichotomous outcome measures from continuous data in randomised controlled trials of analgesics: verification from independent data. Pain 1997;69(1‐2):127‐30. [DOI: 10.1016/S0304-3959(96)03251-4] - DOI - PubMed
Moore 1997c
    1. RA Moore, H McQuay. Single‐patient data meta‐analysis of 3,453 postoperative patients: oral tramadol versus placebo, codeine and combination analgesics. Pain 1997;69:287‐94. [DOI: 10.1016/S0304-3959(96)03291-5] - DOI - PubMed
Moore 1998
    1. Moore RA, Gavaghan D, Tramer MR, Collins SL, McQuay HJ. Size is everything‐large amounts of information are needed to overcome random effects in estimating direction and magnitude of treatment effects. Pain 1998;78(3):209‐16. [DOI: 10.1016/S0304-3959(98)00140-7] - DOI - PubMed
Moore 2003
    1. Moore RA, Edwards J, Barden J, McQuay HJ. Bandolier's Little Book of Pain. Oxford: Oxford University Press, 2003. [ISBN: 0‐19‐263247‐7]
Moore 2005
    1. Moore RA, Edwards JE, McQuay HJ. Acute pain: individual patient meta‐analysis shows the impact of different ways of analysing and presenting results. Pain 2005;116(3):322‐31. [DOI: 10.1016/j.pain.2005.05.001] - DOI - PubMed
Moore 2006
    1. Moore A, McQuay H. Bandolier's Little Book of Making Sense of the Medical Evidence. Oxford: Oxford University Press, 2006. [ISBN: 0‐19‐856604‐2]
Moore 2008
    1. Moore RA, Barden J. Systematic review of dexketoprofen in acute and chronic pain. BMC clinical pharmacology 2008;8(1):11. [DOI: 10.1186/1472-6904-8-11] - DOI - PMC - PubMed
Morris 1995
    1. Morris JA, Gardner MJ. Calculating confidence intervals for relative risk, odds ratio and standardised ratios and rates. In: Gardner MJ, Altman DG editor(s). Statistics with Confidence ‐ Confidence Intervals and Statistical Guidelines. London: British Medical Journal, 1995:50‐63. - PMC - PubMed
PCA 2007
    1. Anonymous. Prescription Cost Analysis, England. Department of Health, 2007.
Roy 2007
    1. Roy YM, Derry S, Moore RA. Single dose oral lumiracoxib for postoperative pain. Cochrane Database of Systematic Reviews 2007, Issue 4. [DOI: 10.1002/14651858.CD006865] - DOI - PMC - PubMed
Toms 2008
    1. Toms L, McQuay HJ, Derry S, Moore RA. Single dose oral paracetamol (acetaminophen) for postoperative pain in adults. Cochrane Database of Systematic Reviews 2008, Issue 4. [DOI: 10.1002/14651858.CD004602] - DOI - PMC - PubMed

Publication types