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T
he strategy of combining
two analgesic agents having
distinct mechanisms or sites AB STRACT
J
A D
A
of action, such as combining Background. Effective and safe drug therapy
N
CON
a peripherally acting analgesic with for the management of acute postoperative pain
IO
a centrally acting analgesic, has
T
has relied on orally administered analgesics
A
N
I
U C
2
TIC LE
A common example is the analgesic or N-acetyl-p-aminophenol (APAP), as well as
formulation containing acetamino- combination formulations containing opioids such as hydrocodone
phen, or N-acetyl-p-aminophenol with APAP. The combination of ibuprofen and APAP has been
(APAP), combined with the opioid advocated in the last few years as an alternative therapy for
hydrocodone (for example, Vicodin postoperative pain management. The authors conducted a
[Abbott Laboratories, Abbott Park, critical analysis to evaluate the scientific evidence for using the
Ill.] or Lorcet [UCB, Atlanta]). This ibuprofen-APAP combination and propose clinical treatment
combination is the most frequently recommendations for its use in managing acute postoperative
prescribed drug in the United pain in dentistry.
States.5 Analgesic formulations con- Types of Studies Reviewed. The authors used quantitative
taining an opioid and a peripherally evidence-based reviews published by the Cochrane Collaboration
acting analgesic consistently provide to determine the relative analgesic efficacy and safety of
greater pain relief than do the com- combining ibuprofen and APAP. They found additional articles by
ponent agents when administered searching the Ovid MEDLINE, PubMed and ClinicalTrials.gov
alone.3,4,6-9 In a Cochrane systematic databases.
review of 20 high-quality clinical tri- Conclusions. The results of the quantitative systematic reviews
als, investigators also confirmed the indicated that the ibuprofen-APAP combination may be a more
additive pain relief that occurs when effective analgesic, with fewer untoward effects, than are many of
combining the opioid oxycodone with the currently available opioid-containing formulations. In addition,
APAP.10 the authors found several randomized controlled trials that also
Including an opioid as part of indicated that the ibuprofen-APAP combination provided greater
an analgesic combination formula- pain relief than did ibuprofen or APAP alone after third-molar
tion, however, increases the risk of extractions. The adverse effects associated with the combination
patients experiencing adverse ef- were similar to those of the individual component drugs.
fects such as nausea, vomiting and Practical Implications. Combining ibuprofen with APAP
psychomotor impairment; restricts provides dentists with an additional therapeutic strategy for
the use of central nervous system managing acute postoperative dental pain. This combination has
depressants; and carries significant been reported to provide greater analgesia without significantly
increasing the adverse effects that often are associated with
risk of experiencing drug misuse
opioid-containing analgesic combinations. When making stepwise
Dr. Moore is a professor of pharmacology and dental
recommendations for the management of acute postoperative
public health, and the chair, Department of Dental dental pain, dentists should consider including ibuprofen-APAP
Anesthesiology, School of Dental Medicine, University combination therapy.
of Pittsburgh, Pittsburgh, Pa. 15261, e-mail pam7@pitt.
edu. Address reprint requests to Dr. Moore.
Key Words. Ibuprofen; acetaminophen; analgesics; drug
Dr. Hersh is a professor of pharmacology, Department combinations; practice guidelines.
of Oral Surgery and Pharmacology, School of Dental JADA 2013;144(8):898-908.
Medicine, University of Pennsylvania, Philadelphia.
action also could be explained by the COX- other, resulting in higher plasma concentrations
inhibitory activity of ibuprofen and nonCOX- and greater efficacy. An assessment of potential
related mechanisms of APAP. ibuprofen and APAP pharmacokinetic drug in-
Both APAP and ibuprofen are indicated for teractions was published in 2010.42 The authors
the management of mild and moderate pain.18 concluded that there were no apparent differ-
Their utility when used as the sole analgesic ences in calculated pharmacokinetic parameters
(monotherapy) for managing severe pain appears (clearance, volume of distribution, absorption
to be limited owing to potential toxicity and an half-life, maximum concentration and time to
apparent ceiling effect seen at high dosages.11,20 maximum concentration) between the compo-
nents administered alone and the ibuprofen-
RATIONALE FOR ANALGESIC APAP combination.
COMBINATIONS A third possible mechanism for improved
Orally administered analgesics are the primary analgesia with analgesic combinations is that
drug therapy used to manage acute postopera- one agent alters the nociceptive sensitivity of
tive pain in dentistry. Because monotherapy the other agent. For example, after administra-
often provides inadequate pain relief, investi- tion of an NSAID, expression of an altered form
gators have advocated combinations of two or of COX enzymes may occur, and this alteration
more analgesic drugs.1,2,4,39 has greater sensitivity to APAP.43 Augmenting
Beaver40 proposed six potential advantages of sensitivity could explain a supra-additive (syn-
formulating drug combinations when treating ergistic) drug interaction.
acute pain: improve analgesic efficacy, decrease Genetic differences among patients is the
adverse reactions, lower costs, treat disorders fourth possible mechanism to explain greater
having multiple symptoms, improve patient analgesia when administering a combination of
adherence and facilitate absorption. The most analgesics. Genetic variations in sensitivity or
valuable advantage for combining ibuprofen and metabolism may result in a patients having a
APAP is the potential to improve analgesic effi- better response to one agent than to another.43,44
cacy without increasing the incidence of adverse Genetic polymorphisms may result in some
drug reactions. patients not having the specific metabolic en-
There are four possible mechanisms that zymes required when administering prodrugs
might explain why a combination of analgesic such as many of the opioids.45-48 In addition to a
drugs might improve pain relief. The first is combination of two analgesics providing addi-
that there may be additive effects when us- tive analgesic effects, there is a greater likeli-
ing two analgesic agents that have different hood that at least one of the agents will provide
mechanisms.39,41 As investigators in a Cochrane pain relief. This pharmacological concept has
systematic review reported, the commonly pre- been described as cross-firing (or the more
scribed fixed-dose formulations containing an popular term today, multimodal analgesia)
opioid (oxycodone) combined with a peripherally and justifies the use of oral analgesic formula-
acting analgesic (APAP) have consistently dem- tions containing an opioid, such as hydrocodone
onstrated this additive analgesic effect.10 A 2011 in combination with APAP.39,40,49
report of the most frequently prescribed drugs Until as recently as 2010, the number of
in the United States ranked 10 analgesic agents published clinical trials in which investigators
in the Top 200.5 Three of these analgesics were evaluated the additive analgesic efficacy when
formulations containing APAP combined with APAP was combined with any of the NSAIDs
the opioid analgesics hydrocodone, oxycodone were limited and varied greatly regarding the
and codeine. These three combinations ranked NSAIDs selected, the severity of pain and the
as the first, 45th and 138th most frequently types of surgery.13,14,50-52 An early example of an
prescribed, respectively. Among practicing oral APAP-NSAID combination is aspirin combined
and maxillofacial surgeons in the United States with APAP.53 This combination usually is not
in 2006, the most frequently recommended recommended for postoperative pain manage-
prescription analgesics for managing pain after ment in dentistry because of aspirins known
third-molar extractions were APAP-hydrocodone ability to inhibit platelet aggregation and the
(for example, Vicodin) and APAP-oxycodone (for potential for increased postoperative bleeding
example, Percocet [Endo Pharmaceuticals, Mal- and ecchymosis after surgery.54,55 Investigators
vern, Pa.]).16 in studies regarding this combination generally
A second possible mechanism for improved have not seen an added benefit in pain relief
analgesia is the unlikely possibility that one of when they compared it with the maximum dos-
the agents alters the pharmacokinetics of the es of either agent alone.49,53 In addition, there is
little indication that the lower doses of aspirin (NNT), which has been defined as the number
and APAP used in this combination decrease the of patients needed to be treated to obtain one
incidence of adverse effects.17 additional patient achieving at least 50 percent
Investigators in two studies evaluated the maximum pain relief over four to six hours
added pain relief associated with a combina- compared with placebo.18 The lower the NNT,
tion of the NSAID diclofenac and APAP.13,51 For the more effective the analgesic drug therapy.
example, Breivik and colleagues51 evaluated the In addition, we derived research reports that
analgesic efficacy of a combination of diclofenac may have appeared in the literature since these
100 mg and APAP 1,000 mg in a group of 120 systematic reviews were performed from Ovid
patients undergoing third-molar extractions. MEDLINE, PubMed and Clinicaltrials.gov.
Diclofenac 100 mg is an NSAID commonly Furthermore, we scrutinized the reference lists
prescribed in Europe, and it is approximately for published RCTs to ensure no recent clinical
equivalent to a dose of 800 mg of ibuprofen.11 In- research studies were overlooked.
vestigators evaluated analgesic efficacy for eight The Cochrane Database of Systematic Re-
hours after participants underwent third-molar views contains 59 reviews categorized as phar-
extractions by recording pain intensity by using macological treatments for anesthesia and pain
a visual analog scale and pain relief by using control; authors of 38 of these reviews evalu-
a categorical pain scale. Participants who re- ated single-dose oral analgesics for treatment
ceived the combination of diclofenac and APAP of acute pain.56 A published overview of these
had significantly less pain than did those who 38 systematic reviews included results specific
received the individual components (100 mg of to dental pain studies (primarily employing the
diclofenac or 1,000 mg of APAP) or a combina- third-molar extraction model).18 Similarly, data
tion of APAP and codeine. Compared with the from two large dental pain studies published
nonopioid analgesics diclofenac, APAP and the in 2010 and 2011 in which investigators evalu-
diclofenac-APAP combination, the combination ated the analgesic efficacy of an ibuprofen-APAP
containing codeine led to adverse drug reactions combination57,58 were used to calculate the
more frequently (P = .037).51 combinations NNT.44,59 We provide the relative
Similarly, the authors of a 2010 qualitative analgesic efficacy for single-dose agents and
review reported the added benefit of APAP when combinations commonly used in dentistry on
used in combination with several NSAIDs, the basis of these calculated NNT values in
including ibuprofen, diclofenac, ketoprofen, ke- Table 1.10,18,44,59,60
torolac, aspirin, tenoxicam and rofecoxib.52 The In addition to the two studies used to estab-
review included 21 human studies of postopera- lish the NNT for the ibuprofen-APAP combina-
tive pain relief experienced after different types tion,57,58 we identified through our search of
of surgery. The conclusion of this review was the literature two additional RCTs in which
that the combination of APAP and an NSAID investigators assessed the analgesic efficacy
may provide analgesia superior to that of either and safety of the combination after third-molar
drug alone. extractions.42,61 The research design and descrip-
tion of these four studies in which investigators
INFORMATION SUPPORTING IBUPROFEN- evaluated the ibuprofen-APAP combination are
ACETAMINOPHEN COMBINATIONS presented in Table 242,57,58,61 (page 903).
IN DENTISTRY The authors of a study who compared the
To determine the clinical research evidence sup- ibuprofen-APAP combination formulated with
porting the use of an ibuprofen-APAP analgesic ibuprofen 300 mg and APAP 1,000 mg also eval-
drug combination, we sourced systematic, quan- uated it for pain management after third-molar
titative, evidence-based reviews published by extraction.42 They administered analgesics
the Cochrane Collaboration in which investiga- preoperatively and every six hours for 48 hours
tors assessed the efficacy and safety of NSAIDs, postoperatively. They assessed pain intensity
APAP and analgesic combinations when admin- by using a 100-millimeter visual analog scale at
istered to manage postoperative dental pain. four-hour intervals during the 48-hour postop-
The authors of these quantitative systematic erative evaluation. The authors found the group
reviews assessed the quality of all available receiving the ibuprofen-APAP combination had
RCTs for a specific analgesic agent, conducted a significantly less pain than did either the group
meta-analysis and calculated a common statis- using ibuprofen alone (P = .003) or that using
tic to allow for comparisons between analgesic APAP alone (P = .007).42
agents. The calculated statistic the authors used Mehlisch and colleagues57,58 conducted two
for these reviews was number needed to treat separate studies in which they evaluated vari-
3
MEAN PAIN RELIEF
400 mg of ibuprofen
with 1,000 mg of APAP
200 mg of ibuprofen
with 500 mg of APAP
2 1,000 mg of APAP
400 mg of ibuprofen
Placebo
0
60 120 180 240 300 360 420 480
MINUTES AFTER DOSING
Figure 1. Pain relief of ibuprofen-acetaminophen combinations. Pain relief was recorded on a five-point scale, in which 0 indicated
none, 1 indicated a little, 2 indicated some, 3 indicated a lot and 4 indicated complete. APAP: Acetaminophen, or N-acetyl-
p-aminophenol. mg: Milligrams. Adapted with permission of Elsevier from Mehlisch and colleagues.57
by APAP has been reported when a daily dose tion containing ibuprofen instead of APAP
of 4,000 mg is exceeded.67 To prevent excessive (such as Vicoprofen [AbbVie, North Chicago,
consumption of APAP, the FDA has requested Ill.] or its generic equivalent) may be more
that the dose of APAP contained in prescription appropriate.71
opioid-APAP analgesics be limited to a maxi- For use after procedures other than
mum of 325 mg.68 Consequently, formulations third-molar extractions. In dentistry, the
that previously contained 750 mg of APAP and additive effects of an ibuprofen-APAP combina-
7.5 mg of hydrocodone, such as Vicodin HP tion have been studied most often by using the
(Abbott Laboratories), have been reformulated third-molar extraction pain model. This pro-
to contain 300 mg of APAP and 7.5 mg of cedure frequently is performed in young adults
hydrocodone.69 who have no pre-existing infections or ongoing
When prescribing APAP for the management pain. After receiving endodontic therapy for
of acute postoperative pain, dentists must be pulpal necrosis, patients did not consistently
careful to limit the dosing regimen to avoid report improved analgesia as has been reported
potential overdose. Although a reduction in by patients who have undergone third-molar ex-
APAPs total daily dose has not been mandated tractions.63,72 Patients having pain before treat-
by the FDA, continuing concerns about poten- ment and severe postoperative pain may need
tial hepatic toxicity have resulted in McNeil- alternative analgesic strategies that include
PPC, the manufacturer of Tylenol, voluntarily opioids.72-74
reducing its APAP daily dose recommendation The efficacies of APAP, ibuprofen and other
from 4,000 to 3,000 mg.70 Although a single dose NSAIDs differ depending on the surgical model
of 1,000 mg of APAP may be tolerated, multiple being studied (for example, abdominal, gyneco-
daily doses of APAP should not exceed 500 mg logic, orthopedic and dental).14 Within dentistry,
every four hours or 650 mg every six hours. additional research evaluating postoperative
Dentists should warn patients to follow dos- pain management with this combination is
ing instructions and inform them about how to needed for endodontic, periodontic and implant
avoid using many of the other OTC formula- procedures.
tions that contain APAP.67 In addition, if a res- Medical considerations. Although short-
cue medication containing an opioid is believed term use of ibuprofen and APAP are considered
to be warranted, an equally effective formula- safe for most patients, the use of these agents,
5
SUM OF PAIN INTENSITY DIFFERENCE
4
AND PAIN RELIEF SCORE
400 mg of ibuprofen
with 1,000 mg of APAP
3 200 mg of ibuprofen
with 500 mg of APAP
400 mg of ibuprofen with
25.6 mg of codeine
2 1,000 mg of APAP with
30 mg of codeine
Placebo
0
60 120 180 240 300 360 420 480
MINUTES AFTER DOSING
either alone or in combination, may be contrain- NNT for the combination of 10 mg of oxycodone
dicated in those with certain medical histories. and 650 mg of APAP (2.3) and the NNT for the
Administering ibuprofen or any of the NSAIDs combination of 60 mg of codeine and 1,000 mg
to patients receiving warfarin or other antico- of APAP (2.2) are not significantly better than
agulant medications may not be appropriate.17 the NNTs for 400 mg of ibuprofen (2.3), 500 mg
Patients who are regularly taking low-dose as- of naproxen (1.8) or the combination of 200 mg
pirin to prevent myocardial infarction should be of ibuprofen and 500 mg of APAP (1.6).10,18,44,59,60
advised to delay taking an NSAID for 30 to 60 The demonstration that a combination of 200
minutes after taking aspirin because of the re- mg of ibuprofen with 500 mg of APAP can pro-
ported potential of the NSAID to interfere with vide equivalent analgesia after dental surgery
the cardioprotective effect of low-dose aspirin.75 without the adverse effects associated with opi-
In addition, prolonged administration of oid combinations may be clinically beneficial.59
APAP and ibuprofen has gastrointestinal and This nonopioid alternative to opioid-containing
cardiovascular risks.76 Because the mechanisms analgesics may be an effective strategy for pre-
of the analgesic action of APAP and ibuprofen venting potential prescription drug abuse and
may be complementary, concern regarding the diversion, which is a national concern associ-
potential additive risks, particularly at high ated with dispensing prescription drugs.12,77
doses and with long-term administration of the Adjuncts to minimize postoperative
combination, has been published.37 discomfort. Prescribing oral analgesics after
Limiting the need for opioid-containing surgery should not be the sole strategy for post-
analgesic combinations. The improved anal- operative pain control. Adjunctive pain control
gesic efficacy seen when the common OTC an- therapies can limit postoperative discomfort to
algesics ibuprofen and APAP are combined may an extent that severe pain is less likely. The use
provide a therapeutic alternative to opioid- of the long-acting local anesthetic bupivacaine to
containing analgesics. Prescribers may find provide extended soft-tissue and periosteal an-
that routinely providing a prescription for Vi- esthesia is an effective strategy for limiting the
codin or Percocet is not necessary, and even if need for oral analgesics.78-80 The use of the corti-
an opioid combination prescription is needed, costeroid dexamethasone is effective in limiting
fewer pills may be needed or a lower dose of opi- trismus, swelling and pain after third-molar
oid may be sufficient (for example, Vicodin in- surgery.81-83 In addition, the use of peripherally
stead of Vicodin HP). Table 1 indicates that the acting analgesics such as ibuprofen or naproxen
Acad Med Singapore 1991;20(1):9-12. Administration. Organ-specific warnings: internal analgesic, anti-
46. Crews KR, Gaedigk A, Dunnenberger HM, et al. Clinical pyretic, and antirheumatic drug products for over-the-counter hu-
Pharmacogenetics Implementation Consortium (CPIC) guidelines man usefinal monograph, final rule. Fed Regist 2009;74(81):19385-
for codeine therapy in the context of cytochrome P450 2D6 (CYP2D6) 19409.
genotype. Clin Pharmacol Ther 2012;91(2):321-326. 66. Larson AM, Polson J, Fontana RJ, et al. Acetaminophen-
47. Gasche Y, Daali Y, Fathi M, et al. Codeine intoxication asso- induced acute liver failure: results of a United States multicenter,
ciated with ultrarapid CYP2D6 metabolism. N Engl J Med 2004; prospective study. Hepatology 2005;42(6):1364-1372.
351(27):2827-2831. 67. Guggenheimer J, Moore PA. The therapeutic applications and
48. Ciszkowski C, Madadi P, Phillips MS, Lauwers AE, Koren G. risks associated with acetaminophen use: a review and update.
Codeine, ultrarapid metabolism genotype, and postoperative death. JADA 2011;142(1):38-44.
N Engl J Med 2009;361(8):827-828. 68. U.S. Food and Drug Administration. Acetaminophen pre-
49. Beaver WT. Aspirin and acetaminophen as constituents of scription products limited to 325 mg per dosage unit: drug safety
analgesic combinations. Arch Intern Med 1981;141(3 special num- communication. www.fda.gov/Safety/MedWatch/SafetyInformation/
ber):293-300. SafetyAlertsforHumanMedicalProducts/ucm239955.htm. Accessed
50. Akural EI, Jrvimki V, Lnsineva A, Niinimaa A, Alahuhta May 13, 2013.
S. Effects of combination treatment with ketoprofen 100 mg + 69. AbbVie. Reformulated Vicodin is now available. www.vicodin.
acetaminophen 1000 mg on postoperative dental pain: a single-dose, com/hcp/?cid=ppc_ppd_vcdn_ggl_ppc_0237. Accessed May 17, 2013.
10-hour, randomized, double-blind, active- and placebo-controlled 70. New TYLENOL Dosing Instructions. www.getreliefresponsibly.
clinical trial. Clin Ther 2009;31(3):560-568. com/instructions/instructions.php. Accessed May 13, 2013.
51. Breivik EK, Barkvoll P, Skovlund E. Combining diclofenac 71. Litkowski LJ, Christensen SE, Adamson DN, Van Dyke T, Han
with acetaminophen or acetaminophen-codeine after oral surgery: SH, Newman KB. Analgesic efficacy and tolerability of oxycodone 5
a randomized, double-blind single-dose study. Clin Pharmacol Ther mg/ibuprofen 400 mg compared with those of oxycodone 5 mg/acet-
1999;66(6):625-635. aminophen 325 mg and hydrocodone 7.5 mg/acetaminophen 500 mg
52. Ong CK, Seymour RA, Lirk P, Merry AF. Combining paraceta- in patients with moderate to severe postoperative pain: a random-
mol (acetaminophen) with nonsteroidal antiinflammatory drugs: a ized, double-blind, placebo-controlled, single-dose, parallel-group
qualitative systematic review of analgesic efficacy for acute postop- study in a dental model. Clin Ther 2005;27(4):418-429.
erative pain. Anesth Analg 2010;110(4):1170-1179. 72. Wells LK, Drum M, Nusstein J, Reader A, Beck M. Efficacy of
53. Wallenstein SL. Analgesic studies of aspirin in cancer patients. ibuprofen and ibuprofen/acetaminophen on postoperative pain in
In: Proceedings of the Aspirin Symposium: Held at the Royal College symptomatic patients with a pulpal diagnosis of necrosis. J Endod
of Surgeons, London on May 30, 1975. London: Aspirin Foundation; 2011;37(12):1608-1612.
1975:5-10. 73. Nist E, Reader A, Beck M. An evaluation of apical trephination
54. Heps HU, Lkken P, Bjrnson J, Godal HC. Double-blind on postoperative pain and swelling in symptomatic necrotic teeth. J
crossover study of the effect of acetylsalicylic acid on bleeding and Endod 2001;27(6):415-420.
postoperative course after bilateral oral surgery. Eur J Clin 74. Nusstein JM, Reader A, Beck M. Effect of drainage upon ac-
Pharmacol 1976;10(3-4):217-225. cess on postoperative endodontic pain and swelling in symptomatic
55. Skjelbred P, Album D, Lokken P. Acetylsalicylic acid vs para- necrotic teeth. J Endod 2002;28(8):584-588.
cetamol: effects on post-operative course. Eur J Clin Pharmacol 1977; 75. U.S. Food and Drug Administration. Information for healthcare
12(4):257-264. professionals: concommitant use of ibuprofen and aspirin. www.fda.
56. The Cochrane Library. Cochrane Reviews: Pharmacological gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationfor
Treatment. www.thecochranelibrary.com/details/browseReviews/ PatientsandProviders/ucm125222.htm. Accessed May 13, 2013.
577365/Pharmacological-treatment.html. Accessed May 28, 2013. 76. Garca Rodriguez LA, Hernndez-Daz S. Relative risk of upper
57. Mehlisch DR, Aspley S, Daniels SE, Bandy DP. Comparison of gastrointestinal complications among users of acetaminophen and
the analgesic efficacy of concurrent ibuprofen and paracetamol with nonsteroidal anti-inflammatory drugs. Epidemiology 2001;12(5):
ibuprofen or paracetamol alone in the management of moderate to 570-576.
severe postoperative dental pain in adolescents and adults: a random- 77. Oakley M, ODonnell J, Moore PA, Martin J. The rise in pre-
ized, double-blind, placebo-controlled, parallel-group, single-dose, scription drug abuse: raising awareness in the dental community.
two-center, modified factorial study. Clin Ther 2010;32(5):882-895. Compend Contin Educ Dent 2011;32(6):14-16, 18-22.
58. Mehlisch DR, Aspley S, Daniels SE, et al. A single-tablet fixed- 78. Gordon SM, Brahim JS, Dubner R, McCullagh LM, Sang C,
dose combination of racemic ibuprofen/paracetamol in the manage- Dionne RA. Attenuation of pain in a randomized trial by suppression
ment of moderate to severe postoperative dental pain in adult and of peripheral nociceptive activity in the immediate postoperative
adolescent patients: a multicenter, two-stage, randomized, double- period. Anesth Analg 2002;95(5):1351-1357.
blind, parallel-group, placebo-controlled, factorial study. Clin Ther 79. Moore PA. Bupivacaine: a long-lasting local anesthetic for den-
2010;32(6):1033-1049. tistry. Oral Surg Oral Med Oral Pathol 1984;58(4):369-374.
59. Derry S, Wiffen PJ, Moore RA. Relative efficacy of oral 80. Moore PA. Long-acting local anesthetics: a review of clinical
analgesics after third molar extractions: a 2011 update. Br Dent J efficacy in dentistry. Compendium 1990;11(1):22, 24-26, 28-30.
2011;211(9):419-420. 81. Moore PA, Brar P, Smiga ER, Costello BJ. Preemptive rofecoxib
60. Derry C, Derry S, Moore RA, McQuay HJ. Single dose oral and dexamethasone for prevention of pain and trismus following
naproxen and naproxen sodium for acute postoperative pain in third molar surgery. Oral Surg Oral Med Oral Pathol Oral Radiol
adults. Cochrane Database Syst Rev 2009;(1):CD004234. Endod 2005;99(2):E1-E7.
61. Daniels SE, Goulder MA, Aspley S, Reader S. A randomised, 82. Misch CE, Moore P. Steroids and the reduction of pain,
five-parallel-group, placebo-controlled trial comparing the efficacy edema and dysfunction in implant dentistry. Int J Oral Implantol
and tolerability of analgesic combinations including a novel single- 1989;6(1):27-31.
tablet combination of ibuprofen/paracetamol for postoperative dental 83. Truollos ES, Hargreaves KM, Butler DP, et al. Comparison of
pain. Pain 2011;152(3):632-642. nonsteroidal anti-inflammatory drugs, ibuprofen and flurbiprofen,
62. McQuay HJ, Derry S, Eccleston C, Wiffen PJ, Moore RA. methylprednisolone and placebo for acute pain, swelling, and tris-
Evidence for analgesic effect in acute pain: 50 years on. Pain mus. J Oral Maxillofac Surg 1990;48(9):945-952.
2012;153(7):1364-1367. 84. Dionne RA, Cooper SA. Evaluation of preoperative ibuprofen
63. Menhinick KA, Gutmann JL, Regan JD, Taylor SE, Buschang for postoperative pain after removal of third molars. Oral Surg Oral
PH. The efficacy of pain control following nonsurgical root canal Med Oral Pathol 1978;45(6):851-856.
treatment using ibuprofen or a combination of ibuprofen and acet- 85. Jackson DL, Moore PA, Hargreaves KM. Preoperative nonste-
aminophen in a randomized, double-blind, placebo-controlled study. roidal anti-inflammatory medication for the prevention of postopera-
Int Endod J 2004;37(8):531-541. tive dental pain. JADA 1989;119(5):641-647.
64. Hersh EV, Cooper S, Betts N, et al. Single dose and multidose 86. Hersh EV, Kane WT, ONeil MG, et al. Prescribing recommen-
analgesic study of ibuprofen and meclofenamate sodium after third dations for the treatment of acute pain in dentistry. Compend Contin
molar surgery. Oral Surg Oral Med Oral Pathol 1993;76(6):680-687. Educ Dent 2011;32(3):22, 24-30.
65. Department of Health and Human Services, Food and Drug