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
Meta-Analysis
. 2009 Jan 21;2009(1):CD001547.
doi: 10.1002/14651858.CD001547.pub2.

Single dose oral paracetamol (acetaminophen) with codeine for postoperative pain in adults

Laurence Toms  1 , Sheena Derry, R Andrew Moore, Henry J McQuay
Affiliations
Meta-Analysis

Single dose oral paracetamol (acetaminophen) with codeine for postoperative pain in adults

Laurence Toms et al. Cochrane Database Syst Rev. .

Abstract

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 strategy: 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.

PubMed Disclaimer

Conflict of interest statement

LT has no interests to declare. RAM and HJM have consulted for various pharmaceutical companies. RAM and HJM and have received lecture fees from pharmaceutical companies related to analgesics and other healthcare interventions. SD, RAM and HJM have received research support from charities, government and industry sources at various times: no support other than the declared financial support was received for this work.

Figures

1
1
Forest plot of comparison: 3 Paracetamol 800 to 1000 mg plus codeine 60 mg versus placebo, outcome: 1.1 Participants with at least 50% pain relief over 4 to 6 hours.
2
2
Forest plot of comparison: 5 Paracetamol 600 to 650 mg plus codeine 60 mg versus placebo, outcome: 3.1 Participants with at least 50% pain relief over 4 to 6 hours.
3
3
Forest plot of comparison: 7 Paracetamol 300 mg plus codeine 30 mg versus placebo, outcome: 5.1 Participants with at least 50% pain relief over 4 to 6 hours.
4
4
Forest plot of comparison: 4 Paracetamol 800 to 1000 mg plus codeine 60 mg versus paracetamol 1000 mg, outcome: 2.1 Participants with at least 50% pain relief over 4 to 6 hours.
5
5
Forest plot of comparison: 6 Paracetamol 600 to 650 mg plus codeine 60 mg versus paracetamol 600 to 650 mg, outcome: 4.1 Participants with at least 50% pain relief over 4 to 6 hours.
6
6
Forest plot of comparison: 5 Paracetamol 600 to 650 mg plus codeine 60 mg versus placebo, outcome: 3.4 Participants using rescue medication over 4 to 6 hours.
7
7
Forest plot of comparison: 7 Paracetamol 300 mg plus codeine 30 mg versus placebo, outcome: 5.4 Participants using rescue medication over 4 to 6 hours.
8
8
Forest plot of comparison: 6 Paracetamol 600 to 650 mg plus codeine 60 mg versus paracetamol 600 to 650 mg, outcome: 4.4 Participants using rescue medication over 4 to 6 hours.
9
9
Forest plot of comparison: 8 Paracetamol plus codeine (all doses) versus placebo, outcome: 8.1 Participants with at least one adverse event.
10
10
Forest plot of comparison: 5 Paracetamol 600 to 650 mg plus codeine 60 mg versus placebo, outcome: 3.5 Participants with any adverse event.
11
11
Forest plot of comparison: 9 Paracetamol plus codeine (all doses) versus paracetamol alone, outcome: 9.1 Participants with any adverse event.
1.1
1.1. Analysis
Comparison 1 Paracetamol 800 to 1000 mg plus codeine 60 mg versus placebo, Outcome 1 Participants with at least 50% pain relief over 4 to 6 hours.
1.2
1.2. Analysis
Comparison 1 Paracetamol 800 to 1000 mg plus codeine 60 mg versus placebo, Outcome 2 Participants with any adverse event.
2.1
2.1. Analysis
Comparison 2 Paracetamol 800 to 1000 mg plus codeine 60 mg versus paracetamol 1000 mg, Outcome 1 Participants with at least 50% pain relief over 4 to 6 hours.
2.2
2.2. Analysis
Comparison 2 Paracetamol 800 to 1000 mg plus codeine 60 mg versus paracetamol 1000 mg, Outcome 2 Participants using rescue medication over 4 to 6 hours.
2.3
2.3. Analysis
Comparison 2 Paracetamol 800 to 1000 mg plus codeine 60 mg versus paracetamol 1000 mg, Outcome 3 Participants with any adverse event.
3.1
3.1. Analysis
Comparison 3 Paracetamol 600 to 650 mg plus codeine 60 mg versus placebo, Outcome 1 Participants with at least 50% pain relief over 4 to 6 hours.
3.2
3.2. Analysis
Comparison 3 Paracetamol 600 to 650 mg plus codeine 60 mg versus placebo, Outcome 2 Participants with at least 50% pain relief over 4 to 6 hours, dental.
3.3
3.3. Analysis
Comparison 3 Paracetamol 600 to 650 mg plus codeine 60 mg versus placebo, Outcome 3 Participants with at least 50% pain relief over 4 to 6 hours, other surgery.
3.4
3.4. Analysis
Comparison 3 Paracetamol 600 to 650 mg plus codeine 60 mg versus placebo, Outcome 4 Participants using rescue medication over 4 to 6 hours.
3.5
3.5. Analysis
Comparison 3 Paracetamol 600 to 650 mg plus codeine 60 mg versus placebo, Outcome 5 Participants with any adverse event.
4.1
4.1. Analysis
Comparison 4 Paracetamol 600 to 650 mg plus codeine 60 mg versus paracetamol 600‐650 mg, Outcome 1 Participants with at least 50% pain relief over 4 to 6 hours.
4.2
4.2. Analysis
Comparison 4 Paracetamol 600 to 650 mg plus codeine 60 mg versus paracetamol 600‐650 mg, Outcome 2 Participants with at least 50% pain relief over 4 to 6 hours, dental.
4.3
4.3. Analysis
Comparison 4 Paracetamol 600 to 650 mg plus codeine 60 mg versus paracetamol 600‐650 mg, Outcome 3 Participants with at least 50% pain relief over 4 to 6 hours, other surgery.
4.4
4.4. Analysis
Comparison 4 Paracetamol 600 to 650 mg plus codeine 60 mg versus paracetamol 600‐650 mg, Outcome 4 Participants using rescue medication over 4 to 6 hours.
4.5
4.5. Analysis
Comparison 4 Paracetamol 600 to 650 mg plus codeine 60 mg versus paracetamol 600‐650 mg, Outcome 5 Participants with any adverse event.
5.1
5.1. Analysis
Comparison 5 Paracetamol 300 mg plus codeine 30 mg versus placebo, Outcome 1 Participants with at least 50% pain relief over 4 to 6 hours.
5.2
5.2. Analysis
Comparison 5 Paracetamol 300 mg plus codeine 30 mg versus placebo, Outcome 2 Participants with at least 50% pain relief over 4 to 6 hours, dental.
5.3
5.3. Analysis
Comparison 5 Paracetamol 300 mg plus codeine 30 mg versus placebo, Outcome 3 Participants with at least 50% pain relief over 4 to 6 hours, other surgery.
5.4
5.4. Analysis
Comparison 5 Paracetamol 300 mg plus codeine 30 mg versus placebo, Outcome 4 Participants using rescue medication over 4 to 6 hours.
5.5
5.5. Analysis
Comparison 5 Paracetamol 300 mg plus codeine 30 mg versus placebo, Outcome 5 Participants with any adverse event.
6.1
6.1. Analysis
Comparison 6 Sensitivity analysis (paracetamol with codeine versus placebo), Outcome 1 Fewer than 40 patients in active and placebo groups, participants with at least 50% pain relief over 4 to 6 hours.
6.2
6.2. Analysis
Comparison 6 Sensitivity analysis (paracetamol with codeine versus placebo), Outcome 2 More than 40 patients in active and placebo groups, participants with at least 50% pain relief over 4 to 6 hours.
7.1
7.1. Analysis
Comparison 7 Sensitivity analysis (paracetamol with codeine versus paracetamol), Outcome 1 Fewer than 40 patients in active and control groups, Participants with at least 50% pain relief over 4 to 6 hours.
7.2
7.2. Analysis
Comparison 7 Sensitivity analysis (paracetamol with codeine versus paracetamol), Outcome 2 More than 40 patients in active and control groups, Participants with at least 50% pain relief over 4 to 6 hours.
8.1
8.1. Analysis
Comparison 8 Paracetamol plus codeine (all doses) versus placebo, Outcome 1 Participants with any adverse event.
9.1
9.1. Analysis
Comparison 9 Paracetamol plus codeine (all doses) versus paracetamol alone, Outcome 1 Participants with any adverse event.
See this image and copyright information in PMC

Update of

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

References to studies included in this review

Bentley 1987 {published data only}
    1. Bentley KC, Head TW. The additive analgesic efficacy of acetaminophen, 1000 mg, and codeine, 60 mg, in dental pain. Clinical Pharmacology and Therapeutics 1987;42(6):634‐40. - PubMed
Bjune 1996 {published data only}
    1. Bjune K, Stubhaug A, Dodgson MS, Breivik H. Additive analgesic effect of codeine and paracetamol can be detected in strong, but not moderate, pain after Caesarean section. Baseline pain‐intensity is a determinant of assay‐sensitivity in a postoperative analgesic trial. Acta Anaesthesiologica Scandinavica 1996;40(4):399‐407. - PubMed
Bourne 2005 {published data only}
    1. Bourne MH, Rosenthal NR, Xiang J, Jordan D, Kamin M. Tramadol/acetaminophen tablets in the treatment of postsurgical orthopedic pain. The American Journal of Orthopedics 2005;24(12):592‐7. - PubMed
Breivik 1999 {published data only}
    1. Breivik EK, Barkvoll P, Skovlund E. Combining diclofenac with acetaminophen or acetaminophen‐codeine after oral surgery: A randomized, double‐blind single‐dose study. Clinical Pharmacology and Therapeutics 1999;66(6):625‐35. - PubMed
Chang 2001 {published data only}
    1. Chang DJ, Fricke JR, Bird SR, Bohidar NR, Dobbins TW, Geba GP. Rofecoxib versus codeine/acetaminophen in postoperative dental pain: a double‐blind, randomized, placebo‐ and active comparator‐controlled clinical trial. Clinical Therapeutics 2001;23(9):1446‐55. - PubMed
Chang 2005 {published data only}
    1. Chang DJ, Bird SR, Bohidar NR, King T. Analgesic efficacy of rofecoxib compared with codeine/acetaminophen using a model of acute dental pain. Oral Surgery Oral Medicine Oral Pathology Oral Radiology and Endodontology 2005;100(4):e74‐80. [DOI: 10.1016/j.tripleo.2005.04.026] - DOI - PubMed
Cooper 1981 {published data only}
    1. Cooper SA, Breen JF, Giuliani RL. The relative efficacy of indoprofen compared with opioid analgesic combinations. Journal of Oral Surgery 1981;39(1):21‐5. - PubMed
Cooper 1988 {published data only}
    1. Cooper SA, Firestein A, Cohn P. Double blind comparison of meclofenamate sodium with acetaminophen, acetaminophen with codeine and placebo for relief of postsurgical dental pain. The Journal of Clinical Dentistry 1988;1(2):31‐4. - PubMed
Cooper 1991 {published data only}
    1. Cooper SA, Kupperman A. The analgesic efficacy of flurbiprofen compared to acetaminophen with codeine. The Journal of Clinical Dentistry 1991;2(3):70‐4. - PubMed
Desjardins 1986 {published data only}
    1. Desjardins PJ, Cooper SA, Finizio T. Efficacy of low dose combination analgesics: acetaminophen/codeine, aspirin/butalbital/caffeine/codeine, and placebo in oral surgery pain. Anesthesia Progress 1986;33(3):143‐6. - PMC - PubMed
Dionne 1994 {published data only}
    1. Dionne RA, Snyder J, Hargreaves KM. Analgesic efficacy of flurbiprofen in comparison with acetaminophen, acetaminophen plus codeine, and placebo after impacted third molar removal. Journal of Oral Maxillofacial Surgery 1994;52(9):919‐24. - PubMed
Forbes 1982 {published data only}
    1. Forbes JA, Beaver WT, White EH, White RW, Neilson GB, Shackleford RW. Diflunisal. A new oral analgesic with an unusually long duration of action. The Journal of the American Medical Association 1982;248(17):2139‐42. - PubMed
Forbes 1983 {published data only}
    1. Forbes JA, Kolodny AL, Beaver WT, Shackleford RW, Scarlett VR. A 12 hour evaluation of the analgesic efficacy of diflunisal, acetaminophen, and acetaminophen codeine combination, and placebo in postoperative pain. Pharmacotherapy 1983;3(2 Pt 2):47S‐54S. - PubMed
Forbes 1986 {published data only}
    1. Forbes JA, Jones KF, Smith WK, Gongloff CM. Analgesic effect of an aspirin codeine butalbital caffeine combination and an acetaminophen codeine combination in postoperative oral surgery pain. Pharmacotherapy 1986;6(5):240‐7. - PubMed
Forbes 1989 {published data only}
    1. Forbes JA, Butterworth GA, Burchfield WH, Yorio CC, Selinger LR, Rosenmertz SK, et al. Evaluation of flurbiprofen, acetaminophen, an acetaminophen‐codeine combination, and placebo in postoperative oral surgery pain. Pharmacotherapy 1989;9(5):322‐30. - PubMed
Forbes 1990a {published data only}
    1. Forbes JA, Butterworth GA, Burchfield WH, Beaver WT. Evaluation of ketorolac, aspirin, and an acetaminophen‐codeine combination in postoperative oral surgery pain. Pharmacotherapy 1990;10(6 Pt 2):77S‐93S. - PubMed
Forbes 1990b {published data only}
    1. Forbes JA, Kehm CJ, Grodin CD, Beaver WT. Evaluation of ketorolac, ibuprofen, acetaminophen, and an acetaminophen codeine combination in postoperative oral surgery pain. Pharmacotherapy 1990;10(6 Pt 2):94S‐105S. - PubMed
Forbes 1994 {published data only}
    1. Forbes JA, Bates JA, Edquist IA, Burchfield WH, Smith FG, Schwartz MK, et al. Evaluation of two opioid‐acetaminophen combinations and placebo in postoperative oral surgery pain. Pharmacotherapy 1994;14(2):139‐46. - PubMed
Gertzbein 1986 {published data only}
    1. Gertzbein SD, Tile M, McMurty RY, Kellam JF, Hunter GA, Keith RG, et al. Analysis of the analgesic efficacy of acetaminophen 1000 mg, codeine phosphate 60 mg, and the combination of acetaminophen 1000 mg and codeine phosphate 60 mg in the relief of postoperative pain. Pharmacotherapy 1986;6(3):104‐7. - PubMed
Heidrich 1985 {published data only}
    1. Heidrich G, Slavic Svircev V, Kaiko RF. Efficacy and quality of ibuprofen and acetaminophen plus codeine analgesia. Pain 1985;22(4):385‐97. - PubMed
Honig 1984 {published data only}
    1. Honig S, Murray KA. An appraisal of codeine as an analgesic: single dose analysis. The Journal of Clinical Pharmacology 1984;24(2‐3):96‐102. - PubMed
Malmstrom 2004 {published data only}
    1. Malmstrom K, Kotey P, Coughlin H, Desjardins PJ. A randomized, double‐blind, parallel‐group study comparing the analgesic effect of etoricoxib to placebo, naproxen sodium, and acetaminophen with codeine using the dental impaction pain model. The Clinical Journal of Pain 2004;20(3):147‐55. - PubMed
Pande 1996c {published data only}
    1. Pande AC, Pyke RE, Greiner M, Cooper SA, Benjamin R, Pierce MW. Analgesic efficacy of the K‐receptor agonist, Enadoline, in dental surgery pain. Clinical Neuropharmacology 1996;19(1):92‐7. - PubMed
Smith 2004 {published data only}
    1. Smith AB, Ravikumar TS, Kamin M, Jordan D, Xiang J, Capss‐ Study Group, et al. Combination tramadol plus acetaminophen for postsurgical pain. American Journal of Surgery 2004;187(4):521‐7. - PubMed
Stubhaug 1995 {published data only}
    1. Stubhaug A, Grimstad J, Breivik H. Lack of analgesic effect of 50 mg and 100 mg oral tramadol after orthopaedic surgery: a randomized, double‐blind, placebo and standard active drug comparison. Pain 1995;62(1):111‐8. - PubMed
Sunshine 1986 {published data only}
    1. Sunshine A, Marrero I, Olson N, McCormick N, Laska EM. Comparative study of flurbiprofen, zomepirac sodium, acetaminophen plus codeine, and acetaminophen for the relief of postsurgical dental pain. The American Journal of Medicine 1986;80(3A):50‐4. - PubMed
Turek 1988 {published data only}
    1. Turek MD, Baird WM. Double blind parallel comparison of ketoprofen (Orudis), acetaminophen plus codeine, and placebo in postoperative pain. The Journal of Clinical Pharmacology 1988;28(12 Suppl):S23‐8. - PubMed
Ziccardi 2000 {published data only}
    1. Ziccardi VB, Desjardins PJ, Daly‐DeJoy E, Seng GF. Single‐dose vicoprofen compared with acetaminophen with codeine and placebo in patients with acute postoperative pain after third molar extractions. Journal of Oral and Maxillofacial Surgery : official journal of the American Association of Oral and Maxillofacial Surgeons 2000;58(6):622‐8. - PubMed

References to studies excluded from this review

Becker 1990 {published data only}
    1. Becker J, Beckmann J, Bertelt C, Gundert‐Remy U, Rohmel J, Ohlendorf D. Double blind biometric study on postoperative effects of analgesics [Doppelblindstudie uber postoperative analgetikawirkungen]. Deutsche Zahnarztliche Zeitschrift 1990;45(1):36‐8. - PubMed
Behotas 1992 {published data only}
    1. Behotas S, Chauvin A, Castiel J, Martin A, Boureau F, Barrat J, Lienhart A. Analgesic efficacy of ibuprofen for post‐episiotomy pain [Effets antalgiques de L'ibuprofene dans les doulers apres episiotomie]. Annales Françaises d'Anesthèsie et de Rèanimation 1992;11(1):22‐6. - PubMed
Chung 2004 {published data only}
    1. Chung F, Tong D, Miceli PC, Reiz J, Harsanyi Z, Darke AC, Payne LW. Controlled‐release codeine is equivalent to acetaminophen plus codeine for post‐cholecystectomy analgesia. Canadian Journal of Anaesthesia 2004;51(3):216‐21. - PubMed
Cooper 1984 {published data only}
    1. Cooper SA. Five studies on ibuprofen for postsurgical dental pain. The American Journal of Medicine 1984;Suppl:70‐7. - PubMed
De los Santos 1998 {published data only}
    1. Santos AR, MartÌ MI, Espinosa D, Girolamo G, Vinacur JC, Casadei A. Lysine clonixinate vs. paracetamol/codeine in postepisiotomy pain. Acta Physiologica, Pharmacologica et Therapeutica Latinoamericana 1998;48(1):52‐8. - PubMed
Forbes 1981 {published data only}
    1. Forbes JA, Bowser MW, Calderazzo JP, Foor VM. An evaluation of the analgesic efficacy of three opioid‐analgesic combinations in postoperative oral surgery pain. Journal of Oral Surgery 1981;39:108‐12. - PubMed
Fulkerson 1986 {published data only}
    1. Fulkerson JP, Folcik MA. Analgesia following arthroscopic surgery: comparison of Diflunisal and acetaminophen with codeine. Arthroscopy 1986;2(2):108‐10. - PubMed
Jacobson 1987 {published data only}
    1. Jacobson J, Bertilson SO. Analgesic efficacy of paracetamol/codeine and paracetamol/dextropropoxyphene in pain after episiotomy and ruptures in connection with childbirth. The Journal of International Medical Research 1987;15(2):89‐95. - PubMed
Levin 1974 {published data only}
    1. Levin HM, Bare WW, Berry FN, Miller JM. Acetaminophen with codeine for the relief of severe pain in postpartum patients. Current Therapeutic Research 1974;16(9):921‐7. - PubMed
Maalaki 2002 {published data only}
    1. Maaliki H, Church L. Which is better for the management of postpartum perineal pain: Ibuprofen or acetaminophen with codeine?. The Journal of Family Practice 2002;51(3):207. - PubMed
Macleod 2002 {published data only}
    1. Macleod AG, Ashford B, Voltz M, Williams B, Cramond T, Gorta L, et al. Paracetamol versus paracetamol‐codeine in the treatment of post‐operative dental pain: a randomized, double‐blind, prospective trial. Australian Dental Journal 2002;47(2):147‐51. - PubMed
Matthews 1984 {published data only}
    1. Matthews RW, Scully CM, Levers BG. The efficacy of diclofenac sodium (Voltarol) with and without paracetamol in the control of post surgical dental pain. British Dental Journal 1984;157(10):357‐9. - PubMed
Ottinger 1990 {published data only}
    1. Ottinger ML, Kinney KW, Black JR, Wittenberg M. Comparison of flurbiprofen and acetaminophen with codeine in postoperative foot pain. Journal of the American Podiatry Association 1990;80(5):266‐70. - PubMed
Oullette 1986 {published data only}
    1. Ouellette RD, Feinberg A, Laraja R, et al. Naproxen sodium vs acetaminophen plus codeine in postsurgical pain. Current Therapeutic Research, Clinical and Experimental 1986;39(5):839‐45.
Pande 1996a {published data only}
    1. Pande AC, Pyke RE, Greiner M, Cooper SA, Benjamin R, Pierce MW. Analgesic efficacy of the kappa‐receptor agonist, enadoline, in dental surgery pain. Clinical Neuropharmacology 1996;19(1):92‐7. - PubMed
Pande 1996b {published data only}
    1. Pande AC, Pyke RE, Greiner M, Wideman GL, Benjamin R, Pierce MW. Analgesic efficacy of enadoline versus placebo or morphine in postsurgical pain. Clinical Neuropharmacology 1996;19(5):451‐6. - PubMed
Peter 2001 {published data only}
    1. Peter EA, Janssen PA, Grange CS, Douglas MJ. Ibuprofen versus acetaminophen with codeine for the relief of perineal pain after childbirth: a randomized controlled trial. Canadian Medical Association Journal 2001;165(9):1203‐9. - PMC - PubMed
Petti 1985 {published data only}
    1. Petti A. Postoperative pain relief with pentazocine and acetaminophen: comparison with other analgesic combinations and placebo. Clinical Therapeutics 1985;8(1):126‐33. - PubMed
Quiding 1982a {published data only}
    1. Quiding H, Persson G, Ahlstrom U, Bangens S, Hellem S, Johansson G, et al. Paracetamol plus supplementary doses of codeine. An analgesic study of repeated doses. The Journal of Clinical Pharmacology 1982;23(4):315‐9. - PubMed
Quiding 1983 {published data only}
    1. Quiding H, Haggquist SO. Visual analogue scale and the analysis of analgesic action. The Journal of Clinical Pharmacology 1983;24(4):475‐8. - PubMed
Quiding 1984 {published data only}
    1. Quiding H, Oikarinen V, Sane J, Sjoblad AM. Analgesic efficacy after single and repeated doses of codeine and acetaminophen. The Journal of Clinical Pharmacology 1984 Jan;24(1):27‐34. - PubMed
Raeder 2001 {published data only}
    1. Raeder JC, Steine S, Vatsgar TT. Oral ibuprofen versus paracetamol plus codeine for analgesia after ambulatory surgery. Anesthesia and Analgesia 2001;92(6):1470‐2. - PubMed
Scoren 1987 {published data only}
    1. Scoren RD, Corn H, Rhodes P, Schwarz M, Segal PL, Marks MH. Pain following periodontal surgery treatment with a nonnarcotic analgesic compared with two codeine combinations. Current Therapeutic Research, Clinical and Experimental 1987;42(3):463‐71.
Skjelbred 1977 {published data only}
    1. Skjelbred P, Album B, Lokken P. Acetylsalicylic acid vs paracetamol: effects on postoperative course. European Journal of Clinical Pharmacology 1977;12(4):257‐64. - PubMed
Sunshine 1988 {published data only}
    1. Sunshine A, Olson NZ. Analgesic efficacy of ketoprofen in postpartum, general surgery, and chronic cancer pain. The Journal of Clinical Pharmacology 1988;28:S47‐S54. - PubMed
Sveen 1975 {published data only}
    1. Sveen K, Gilhuus MoeO. Paracetamol/codeine in relieving pain following removal of impacted mandibular third molars. International Journal of Oral Surgery 1975;4(6):258‐66. - PubMed
Torabinejad 1994 {published data only}
    1. Torabinejad M, Dorn SO, Eleazer PD, Frankson M, Jouhari B, Mullin RK, et al. Effectiveness of various medications on postoperative pain following root canal obturation. Journal of Endodontics 1994;20(9):427‐31. - PubMed
Vangen 1988 {published data only}
    1. Vangen O, Doessland S, Lindbaek E. Comparative study of ketorolac and paracetamol/codeine in alleviating pain following gynaecological surgery. The Journal of International Medical Research 1988;16(6):443‐51. - PubMed
Wittenberg 1984 {published data only}
    1. Wittenberg M, Kinney KW, Black JR. Comparison of ibuprofen and acetaminophen codeine in postoperative foot pain. Journal of the American Podiatry Association 1984;74(5):233‐7. - PubMed

Additional references

Botting 2000
    1. RM Botting. Mechanism of action of acetaminophen: is there a cyclooxygenase 3?. Clinical Infectious Diseases 2000;31(5):S203‐S210. - PubMed
Chandrasekharan 2002
    1. NV Chandrasekharan. COX‐3, a cyclooxygenase‐1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure and expression. Proceedings of the National Academy of Sciences of the United States of America 2002;99:13926‐13931. - PMC - PubMed
Clarke in press
    1. Clarke R, Derry S, Moore RA, McQuay HJ. Single dose oral etoricoxib for acute postoperative pain in adults. Cochrane Database of Systematic Reviews In press. - 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 1999
    1. Collins SL, Moore RA, McQuay HJ, Wiffen PJ, Edwards JE. Single dose oral ibuprofen and diclofenac for postoperative pain. Cochrane Database of Systematic Reviews 1999, Issue 1. [DOI: 10.1002/14651858.CD001548] - DOI - PubMed
Collins 2001
    1. Collins SL, Edwards J, Moore RA, Smith L, McQuay HJ. Seeking a simple measure of analgesia for mega trials: is simple global assessment good enough?. Pain 2001;91:189‐94. - PubMed
Cook 1995
    1. Cook RJ, Sackett DL. The number needed to treat: a clinically useful measure of treatment effect. British Medical Journal 1995;310:452‐4. - PMC - PubMed
CSM 1997
    1. Committee on Safety of Medicines. Medicines Control Agency. Paracetamol and aspirin. Current pproblems in Pharmacovigilance 1997;23:9.
Dart 2000
    1. Dart RC, Kuffner EK, Rumack BH. Treatment of pain or fever with paracetamol (acetaminophen) in the alcoholic patient: a systematic review. The American Journal of Medicine 2000;7(2):123‐34. - PubMed
Derry 2008
    1. Derry S, Barden J, McQuay HJ, Moore RA. Single dose oral celecoxib for postoperative pain. Cochrane Database of Systematic Reviews 2008, Issue 4. [DOI: 10.1002/14651858.CD004233] - DOI - PubMed
Edwards 1999
    1. Edwards JE, McQuay HJ, Moore RA, Collins SL. Reporting of adverse effects in clinical trials should be improved: lessons from acute postoperative pain. Journal of Pain and Symptom Management 1999;18(6):427‐37. [DOI: ] - PubMed
Edwards 2002
    1. Edwards JE, McQuay HJ, Moore RA. Combination analgesic efficacy: individual patient data meta‐analysis of single‐dose oral tramadol plus acetaminophen in acute postoperative pain. Journal of Pain and Symptom Management 2002;23(2):121–130. [DOI: 10.1016/S0885-3924(01)00404-3] - DOI - PubMed
Flower 1972
    1. RJ Flower, JR Vane. Inhibition of prostaglandin synthetase in brain explains the anti‐pyretic activity of paracetamol (4‐acetamidophenol). Nature 1972;240:410‐411. - PubMed
Graham 2005
    1. Graham GG, Scott KF. Mechanism of action of paracetamol. American Journal of Therapeutics 2005;12(1):46‐55. - PubMed
Gunnell 1997
    1. D Gunnell, K Hawton, V Garnier, C Bismuth, J Fagg. Use of paracetamol for suicide and non‐fatal poisoning in the UK and France: are restrictions on availability justified?. Journal of Epidemiology and Community Health 1997;51:175‐9. - PMC - PubMed
Hawkins 2007
    1. Hawkins LC, Edwards JN, Dargan PI. Impact of restricting paracetamol pack sizes on paracetamol poisoning in the United Kingdom: a review of the literature. Drug Safety 2007;30(6):465‐79. - PubMed
Hawton 2001
    1. K Hawton, E Townsend, J Deeks, L Appleby, D Gunnell, O Bennewith, J Cooper. Effects of legislation restricting pack sizes of paracetamol and salicylate on self poisoning in the United Kingdom: before and after study. BMJ 2001;322:1‐7. - PMC - PubMed
Hinz 2008
    1. Hinz B, Cheremina O, Brune K. Acetaminophen (paracetamol) is a selective cyclooxygenase‐2 inhibitor in man. FASEB J 2008;22(2):383‐90. - PubMed
Jadad 1996a
    1. Jadad AR, Carroll D, Moore A, McQuay H. Developing a database of published reports of randomised clinical trials in pain research. Pain 1996;66:239‐46. - 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'Abbé 1987
    1. L'Abbé KA, Detsky AS, O'Rourke K. Meta‐analysis in clinical research. Annals of Internal Medicine 1987;107:224‐33. - PubMed
McQuay 1996
    1. McQuay H, Carroll D, Moore A. Variation in the placebo effect in randomised controlled trials of analgesics: all is as blind as it seems. Pain 1996;64(2):331‐5. [DOI: 10.1016/0304-3959(95)00116-6] - DOI - 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;27(354):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. - PubMed
Moore 1997a
    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. - PubMed
Moore 1997b
    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. - PubMed
Moore 1998b
    1. Moore RA, Gavaghan D, Tramèr 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. - 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, Moore OA, Derry S, McQuay HJ. Numbers needed to treat calculated from responder rates give a better indication of efficacy in osteoarthritis trials than mean pain scores. Arthritis Research and Therapy 2008;10(2):R39. [DOI: 10.1186/ar2394] - 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
Oldman 1999
    1. Oldman A, Smith LA, Collins S, Carroll D, Wiffen PJ, McQuay HJ, Rees J, Moore A. Single dose oral aspirin for acute pain. Cochrane Database of Systematic Reviews 1999, Issue 4. [DOI: 10.1002/14651858.CD002067] - DOI - PubMed
PIC 2008
    1. Paracetamol Information Centre. www.pharmweb.net Accessed 3 July 2008.
Prescott 2000
    1. LF Prescott. Therapeutic misadventure with paracetamol: Fact or fiction?. American Journal of Therapeutics 2000;7(2):99‐114. - PubMed
Schwab 2003
    1. JM Schwab, HJ Schluesener, S Laufer. COX‐3: just anothet COX or the solitary elusive target of paracetamol?. The Lancet 2003;361:981‐982. - PubMed
Straube 2008
    1. Straube S, Derry S, McQuay HJ, Moore RA. Enriched enrolment: definition and effects of enrichment and dose in trials of pregabalin and gabapentin in neuropathic pain. A systematic review. British Journal of Clinical Pharmacology 2008;66:266‐75. [DOI: 10.1111/j.1365-2125.2008.03200.x] - 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.pub2] - DOI - PMC - PubMed
Tramèr 1997
    1. Tramèr MR, Reynolds DJM, Moore RA, McQuay HJ. Impact of covert duplicate publication on meta‐analysis: a case study. BMJ 1997;315:635‐40. - PMC - PubMed

References to other published versions of this review

Moore 1997
    1. Moore A, Collins S, Carroll D, McQuay H. Paracetamol with and without codeine in acute pain: a quantitative systematic review. Pain 1997;70:193‐201. - PubMed
Moore 1998a
    1. Moore A, Collins S, Carroll D, McQuay H, Edwards J. Single dose paracetamol (acetaminophen), with and without codeine, for postoperative pain. Cochrane Database of Systematic Reviews 1998, Issue 4. [DOI: 10.1002/14651858.CD001547] - DOI - PubMed

MeSH terms