Ibuprofen and/or paracetamol (acetaminophen) for pain relief after surgical removal of lower wisdom teeth
- PMID: 24338830
- PMCID: PMC11561150
- DOI: 10.1002/14651858.CD004624.pub2
Ibuprofen and/or paracetamol (acetaminophen) for pain relief after surgical removal of lower wisdom teeth
Abstract
Background: Both paracetamol and ibuprofen are commonly used analgesics for the relief of pain following the surgical removal of lower wisdom teeth (third molars). In 2010, a novel analgesic (marketed as Nuromol) containing both paracetamol and ibuprofen in the same tablet was launched in the United Kingdom, this drug has shown promising results to date and we have chosen to also compare the combined drug with the single drugs using this model. In this review we investigated the optimal doses of both paracetamol and ibuprofen via comparison of both and via comparison with the novel combined drug. We have taken into account the side effect profile of the study drugs. This review will help oral surgeons to decide on which analgesic to prescribe following wisdom tooth removal.
Objectives: To compare the beneficial and harmful effects of paracetamol, ibuprofen and the novel combination of both in a single tablet for pain relief following the surgical removal of lower wisdom teeth, at different doses and administered postoperatively.
Search methods: We searched the Cochrane Oral Health Group'sTrials Register (to 20 May 2013); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 4); MEDLINE via OVID (1946 to 20 May 2013); EMBASE via OVID (1980 to 20 May 2013) and the metaRegister of Controlled Trials (to 20 May 2013). We checked the bibliographies of relevant clinical trials and review articles for further studies. We wrote to authors of the identified randomised controlled trials (RCTs), and searched personal references in an attempt to identify unpublished or ongoing RCTs. No language restriction was applied to the searches of the electronic databases.
Selection criteria: Only randomised controlled double-blinded clinical trials were included. Cross-over studies were included provided there was a wash out period of at least 14 days. There had to be a direct comparison in the trial of two or more of the trial drugs at any dosage. All trials used the third molar pain model.
Data collection and analysis: All trials identified were scanned independently and in duplicate by two review authors, any disagreements were resolved by discussion, or if necessary a third review author was consulted. The proportion of patients with at least 50% pain relief (based on total pain relief (TOTPAR) and summed pain intensity difference (SPID) data) was calculated for all three drugs at both two and six hours postdosing and meta-analysed for comparison. The proportion of participants using rescue medication over both six and eight hours was also collated and compared. The number of patients experiencing adverse events or the total number of adverse events reported or both were analysed for comparison.
Main results: Seven studies were included, they were all parallel-group studies, two studies were assessed as at low risk of bias and three at high risk of bias; two were considered to have unclear bias in their methodology. A total of 2241 participants were enrolled in these trials.Ibuprofen was found to be a superior analgesic to paracetamol at several doses with high quality evidence suggesting that ibuprofen 400 mg is superior to 1000 mg paracetamol based on pain relief (estimated from TOTPAR data) and the use of rescue medication meta-analyses. The risk ratio for at least 50% pain relief (based on TOTPAR) at six hours was 1.47 (95% confidence interval (CI) 1.28 to 1.69; five trials) favouring 400 mg ibuprofen over 1000 mg paracetamol, and the risk ratio for not using rescue medication (also favouring ibuprofen) was 1.50 (95% CI 1.25 to 1.79; four trials).The combined drug showed promising results, with a risk ratio for at least 50% of the maximum pain relief over six hours of 1.77 (95% CI 1.32 to 2.39) (paracetamol 1000 mg and ibuprofen 400 mg) (one trial; moderate quality evidence), and risk ratio not using rescue medication 1.60 (95% CI 1.36 to 1.88) (two trials; moderate quality evidence).The information available regarding adverse events from the studies (including nausea, vomiting, headaches and dizziness) indicated that they were comparable between the treatment groups. However, we could not formally analyse the data as it was not possible to work out how many adverse events there were in total.
Authors' conclusions: There is high quality evidence that ibuprofen is superior to paracetamol at doses of 200 mg to 512 mg and 600 mg to 1000 mg respectively based on pain relief and use of rescue medication data collected at six hours postoperatively. The majority of this evidence (five out of six trials) compared ibuprofen 400 mg with paracetamol 1000 mg, these are the most frequently prescribed doses in clinical practice. The novel combination drug is showing encouraging results based on the outcomes from two trials when compared to the single drugs.
Conflict of interest statement
Review authors have no interests to declare.
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Comment in
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Ibuprofen is superior to paracetamol for pain relief following third molar removal.Evid Based Dent. 2014 Dec;15(4):106-7. doi: 10.1038/sj.ebd.6401059. Evid Based Dent. 2014. PMID: 25522940
References
References to studies included in this review
Daniels 2009 {published data only}
-
- Daniels S, Reader S, Berry P, Goulder M. Onset of analgesia with sodium ibuprofen, ibuprofen acid incorporating poloxamer and acetaminophen‐‐a single‐dose, double‐blind, placebo‐controlled study in patients with post‐operative dental pain. European Journal of Clinical Pharmacology 2009;65(4):343‐53. - PubMed
Forbes 1990 {published data only}
-
- 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
Hersh 2000 {published data only}
-
- Hersh EV, Levin LM, Cooper SA, Doyle G, Waksman J, Wedell D, et al. Ibuprofen liquigel for oral surgery pain. Clinical Therapeutics 2000;22(11):1306‐18. - PubMed
Mehlisch 1995 {published data only}
-
- Mehlisch DR, Jasper RD, Brown P, Korn SH, McCarroll K, Murakami AA. Comparative study of ibuprofen lysine and acetaminophen in patients with postoperative dental pain. Clinical Therapeutics 1995;17(5):852‐60. - PubMed
Mehlisch 2010 {published data only}
-
- Mehlisch DR, Aspley S, Daniels SE, Bandy DP. Comparison of the analgesic efficacy of concurrent ibuprofen and paracetamol with ibuprofen or paracetamol alone in the management of moderate to severe acute postoperative dental pain in adolescents and adults: a randomized, double‐blind, placebo‐controlled, parallel‐group, single‐dose, two‐center, modified factorial study. Clinical Therapeutics 2010;32(5):882‐95. - PubMed
Mehlisch 2010a {published data only}
-
- Mehlisch DR, Aspley S, Daniels SE, Southerden KA, Christensen KS. A single‐tablet fixed‐dose combination of racemic ibuprofen/paracetamol in the management of moderate to severe postoperative dental pain in adult and adolescent patients: a multicenter, two‐stage, randomized, double‐blind, parallel‐group, placebo‐controlled, factorial study. Clinical Therapeutics 2010;32(6):1033‐49. - PubMed
Olson 2001 {published data only}
-
- Olson NZ, Otero AM, Marrero I, Tirado S, Cooper S, Doyle G, et al. Onset of analgesia for liquigel ibuprofen 400 mg, acetaminophen 1000 mg, ketoprofen 25 mg, and placebo in the treatment of postoperative dental pain. Journal of Clinical Pharmacology 2001;41(11):1238‐47. - PubMed
References to studies excluded from this review
Bjornsson 2003 {published data only}
Chopra 2009 {published data only}
-
- Chopra D, Rehan HS, Mehra P, Kakkar AK. A randomized, double‐blind, placebo‐controlled study comparing the efficacy and safety of paracetamol, serratiopeptidase, ibuprofen and betamethasone using the dental impaction pain model. International Journal of Oral and Maxillofacial Surgery 2009;38(4):350‐5. - PubMed
Dionne 1983 {published data only}
-
- Dionne RA, Campbell RA, Cooper SA, Hall DL, Buckingham B. Suppression of postoperative pain by preoperative administration of ibuprofen in comparison to placebo, acetaminophen, and acetaminophen plus codeine. Journal of Clinical Pharmacology 1983;23(1):37‐43. - PubMed
Ikeda 2002 {published data only}
-
- Ikeda MC, Arrascue M, Carbajal L, Saravia MA. Ibuprofen, paracetamol and diclofenac plus paracetamol in third molar extractions ‐ a double‐blind post‐operative study. Journal of Dental Research 2002;81(Spec Iss A):A‐316 (Abstract no: 2510).
Merry 2010 {published data only}
Ozkan 2010 {published data only}
-
- Ozkan BT, Durmus E, Kalayci A, Kurban S, Akca CN. The evaluation of safety and analgesic efficacy of paracetamol and ibuprofen followed by impacted third molar surgery. European Journal of General Medicine 2010;7(3):310‐6.
Additional references
Bentley 1987
-
- Bentley KC, Head TW. The additive analgesic efficacy of acetaminophen 1000mg and codeine 60mg in dental pain. Clinical Pharmacology and Therapeutics 1987;42:634‐40. - PubMed
Boers 2001
-
- Boers M. NSAIDs and selective COX‐2 inhibitors: competition between gastroprotection and cardioprotection. Lancet 2001;357(9264):1222‐3. - PubMed
Bromley 2010
-
- Bromley L, Brandner B. Oxford Pain Management Library: Acute Pain. Oxford: Oxford University Press, 2010.
Chandrasekharan 2002
Collins 1999
Colorado‐Bonnin 2006
-
- Colorado‐Bonnin M, Valmaseda‐Castellón E, Berini‐Aytés L, Gay‐Escoda C. Quality of life following lower third molar removal. International Journal of Oral and Maxillofacial Surgery 2006;35(4):343‐7. - PubMed
Conrad 1999
-
- Conrad SM, Blakey GH, Shugars DA, Marciani RD, Phillips C, White RP Jr. Patients' perception of recovery after third molar surgery. Journal of Oral and Maxillofacial Surgery 1999;57(11):1288‐94. - PubMed
Cooper 1976
-
- Cooper SA, Beaver WT. A model to evaluate mild analgesics in oral surgery outpatients. Clinical Pharmacology and Therapeutics 1976;20:241‐50. - PubMed
Coulthard 1992
-
- Coulthard P, Rood JP. An investigation of the effect of midazolam on the pain experience. British Journal of Oral and Maxillofacial Surgery 1992;30:248. - PubMed
Coulthard 1993
-
- Coulthard P, Rood JP. Midazolam and somatosensory evoked potentials. British Journal of Oral and Maxillofacial Surgery 1993;31:28‐31. - PubMed
Coulthard 2009
-
- Coulthard P. Post‐operative oral surgery pain: a review. Oral Surgery 2009;1:167‐77.
Daniels 2011
-
- Daniels SE, Goulder MA, Aspley S, Reader S. A randomised, five‐parallel‐group, placebo‐controlled trial comparing the efficacy and tolerability of analgesic combinations including a novel single‐tablet combination of ibuprofen/paracetamol for postoperative dental pain. Pain 2011;152:632‐42. - PubMed
Derry 2009
Derry 2011
-
- Derry S, Wiffen PJ, Moore RA. Relative efficacy of oral analgesics after third molar extraction – a 2011 update. British Dental Journal 2011;211(9):419‐20. - PubMed
Derry 2013
Dray 1997
-
- Dray A. Kinins and their receptors in hyperalgesia. Canadian Journal of Pharmacology 1997;75:704‐12. - PubMed
Elbourne 2002
-
- Elbourne DR, Altman DG, Higgins JP, Curtin F, Worthington HV, Vail A. Meta‐analyses involving cross‐over trials. International Journal of Epidemiology 2002;31(1):140‐9. - PubMed
Fisher 1988
-
- Fisher SE, Frame JW, Rout PG, McEntegart DJ. Factors affecting the onset and severity of pain following the surgical removal of unilateral impacted third molar teeth. British Dental Journal 1988;164:351‐4. - PubMed
Gobetti 1992
-
- Gobetti JD. Controlling dental pain. Journal of the American Dental Association 1992;123:47‐52. - PubMed
Hersh 2000
-
- Hersh EV, Levin LM, Cooper SA, Doyle G, Waksman J, Wedell D, et al. Ibuprofen liquigel for oral surgery pain. Clinical Therapeutics 2000;22(11):1306‐18. - PubMed
Higgins 2011
-
- Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
Kiersch 1994
-
- Kiersch TA, Halladay SC, Hormel PC. A single‐dose, double‐blind comparison of naproxen sodium, acetaminophen and placebo in postoperative dental pain. Clinical Therapeutics 1994;16:394‐404. - PubMed
Loeser 1999
-
- Loeser JD. Pain: an overview. Lancet 1999;353:1607‐9. - PubMed
Malmberg 1992
-
- Malmberg AB, Yaksh TL. Antinociceptive effects of spinal non‐steroidal anti‐inflammatory agents on the formalin test in the rat. Journal of Pharmacology and Experimental Therapeutics 1992;263:136‐46. - PubMed
McQuay 1998
-
- McQuay H, Moore A. An Evidence Based Resource for Pain. Oxford: Oxford University Press, 1998:187‐92.
Mehlisch 1990
-
- Mehlisch DR, Sollecito WA, Helfrick JF, Leibold DG, Markowitz R, Schow CE Jr, et al. Multicenter clinical trial of ibuprofen and acetaminophen in the treatment of postoperative dental pain. Journal of the American Dental Association 1990;121(2):257‐63. - PubMed
Mehlisch 2002
-
- Mehlisch DR. The efficacy of combination analgesic therapy in relieving dental pain. Journal of the American Dental Association 2002;133:861‐71. - PubMed
Moore 1996
-
- Moore RA, McQuay H, Gavaghan D. Deriving dichotomous outcome measures from continuous data in randomised controlled trials of analgesics. Pain 1996;66:229‐37. - PubMed
Moore 1997
-
- Moore RA, McQuay HJ. Single‐patient data meta‐analysis of 3453 postoperative patients: Oral tramadol versus placebo, codeine and combination analgesics. Pain 1997;69:287‐94. - PubMed
Moore 1997a
-
- Moore RA, 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;69:311‐5. - PubMed
Moore 1997b
-
- Moore RA, McQuay H, Gavaghan D. Deriving dichotomous outcome measures from continuous data in randomised controlled trials of analgesics: verification from independent data. Pain 1997;69:127‐30. - PubMed
Moore 1998
Moore 2011
Neal 2012
-
- Neal MJ. Medical Pharmacology at a Glance. 7th Edition. Oxford: Wiley‐Blackwell, 2012.
Nguyen 1999
-
- Nguyen AM, Graham DY, Gage T, Griffiths GR. Nonsteroidal anti‐inflammatory drug use in dentistry: gastrointestinal implications. General Dentistry 1999;47(6):590‐6. - PubMed
Ogden 1998
-
- Ogden GR, Bissias E, Ruta DA, Ogston S. Quality of life following third molar removal: a patient versus professional perspective. British Dental Journal 1998;185:407‐10. - PubMed
Rang 2012
-
- Rang HP, Dale MM, Ritter JM, Flower RJ, Henderson G. Anti‐inflammatory and immunosuppresant drugs. Pharmacology. 7th Edition. Churchill Livingstone, 2012.
Savin 1997
-
- Savin J, Ogden GR. Third molar surgery‐‐a preliminary report on aspects affecting quality of life in the early postoperative period. British Journal of Oral and Maxillofacial Surgery 1997;35(4):246‐53. - PubMed
Seymour 1985
-
- Seymour RA, Meechan JG, Blair GS. An investigation into post‐operative pain after third molar surgery under local anaesthesia. British Journal of Oral and Maxillofacial Surgery 1985;23:410‐8. - PubMed
Seymour 1998
-
- Seymour RA, Frame J, Negus TW, Hawkesford JE, Marsden J, Matthew IR. The comparative efficacy of aceclofenac and ibuprofen in postoperative pain after third molar surgery. British Journal of Oral and Maxillofacial Surgery 1998;36:375‐9. - PubMed
Toms 2008
Weil 2007
Winter 1978
-
- Winter L, Bass E, Recant B, Cahaly JF. Analgesic activity of ibuprofen (Motrin) in postoperative oral surgery pain. Oral Surgery, Oral Medicine, Oral Pathology 1978;45(2):159‐66. - PubMed
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