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Table of Contents   
ORIGINAL RESEARCH  
Year : 2012  |  Volume : 23  |  Issue : 6  |  Page : 839-840
Sublingual piroxicam in the management of postoperative pain after surgical removal of impacted mandibular third molar


1 Department of Oral and Maxillofacial Surgery, King George University of Dental Sciences, Lucknow, UP, India
2 Meyer Organics Pvt. Ltd, India

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Date of Submission19-Jul-2011
Date of Decision30-Mar-2012
Date of Acceptance27-Apr-2012
Date of Web Publication3-May-2013
 

   Abstract 

Introduction: Surgical removal of impacted mandibular third molar is one of the most commonly performed procedures in oral and maxillofacial surgical practice. The role of preoperative and postoperative medications for management of postoperative complications has been extensively evaluated.
Aim: To assess the therapeutic effect of a single dose of 40 mg sublingual piroxicam (study group) vs 150 mg oral diclofenac (50 mg thrice a day) (control group) in patients undergoing surgical removal of impacted mandibular third molar.
Materials and Methods: A total of 100 patients with asymptomatic impacted mandibular third molars were randomized into two groups. One group received two 20-mg tablets of piroxicam once daily on the first and second postoperative days, followed by one 20-mg tablet on the third post-operative day. The other group received one tablet of diclofenac 50 mg orally thrice daily on the first, second, and third post-operative days. Repeated extraoral examinations were done for continuous assessment of swelling, trismus, and reduction in pain. Ovearall impression of the treating physician and the patient regarding efficacy of study drugs were recorded at the end of the study.
Results: In the piroxicam group there was >50% reduction in pain on all three days postoperatively. The incidence of swelling and trismus was found to be higher in the control group as compared to the study group. Adverse events, such as gastrointestinal (GI) disturbances, were significantly higher in the diclofenac group (11%) as compared to the piroxicam group (0%).
Conclusion: Two sublingual piroxicam 20 mg tablets once daily has better efficacy and tolerability profile than diclofenac 50 mg one tablet thrice daily in the management of pain after surgical removal of impacted mandibular third molar.
Study Title: A Comparative Study to Evaluate Clinical Efficacy and Safety of Sublingual Piroxicam and Diclofenac in the Management of Pain after Surgical Removal of Impacted Mandibular Third Molar.

Keywords: Impacted mandibular third molar, postoperative pain, sublingual piroxicam tablets

How to cite this article:
Mohammad S, Singh V, Wadhwani P, Tayade HP, Rathod OK. Sublingual piroxicam in the management of postoperative pain after surgical removal of impacted mandibular third molar. Indian J Dent Res 2012;23:839-40

How to cite this URL:
Mohammad S, Singh V, Wadhwani P, Tayade HP, Rathod OK. Sublingual piroxicam in the management of postoperative pain after surgical removal of impacted mandibular third molar. Indian J Dent Res [serial online] 2012 [cited 2020 Nov 28];23:839-40. Available from: https://www.ijdr.in/text.asp?2012/23/6/839/111282
A surgical tissue injury induces complex interactions between local inflammatory and general neurohumoral responses, which at the macroscopic level manifests as the five classical signs of inflammation: Heat, redness, swelling, pain, and disturbed function.

Surgical removal of impacted mandibular third molar is the most commonly performed procedure in oral and maxillofacial surgical practice. Pain, swelling, and restricted jaw movements (trismus) are common sequelae of this procedure. Reducing the incidence of these postoperative complications is imperative, [1] and various methods have been suggested, including:

  • Application of external cold dressing [2]
  • Modulating the closure technique
    • Varying the dressing agents [3]
    • Open vs closed dressing [4] (with drain vs without drain)
  • Modulating extent of surgical trauma
    • Skill of the surgeon [5] (resident vs faculty)
    • Surgical technique [6] (chisel vs bur technique)
    • Modifying the flap design [7],[8],[9]
  • Pharmacological methods
    • Anti-inflammatory drugs [10]
    • Analgesics [11] (preoperative/postoperative)
    • Antibacterial mouthwashes [12]
    • Steroid therapy [13] (preoperative/postoperative)
The role of preoperative and postoperative medications in reducing postoperative complications has been extensively evaluated. Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit the synthesis of prostaglandins and reduce the inflammatory reaction and nociceptive stimuli causing reduction in pain. Piroxicam, a NSAID with a long half-life and potent analgesic activity similar to that of indomethacin, [14] has been developed in a new sublingual formulation. It is easily administered and does not have any harmful effects in the oral cavity. Although the analgesic effect of piroxicam in several types of pain (e.g., postoperative pain, acute renal colic, [15] dysmenorrhea, osteoarthritis, [16] low back pain, headache, and migraine [17] ) has been investigated, no studies have evaluated the analgesic efficacy of sublingual piroxicam vs diclofenac after surgical removal of impacted mandibular third molar. Diclofenac sodium is a NSAID that is commonly used in painful conditions like acute postoperative and postextraction dental pain. The present study aimed to evaluate and compare the therapeutic effect of 40 mg of sublingual piroxicam with that of 150 mg of oral diclofenac, a reference drug, in patients undergoing surgical removal of impacted mandibular third molars.


   Materials and Methods Top


This single-center equal randomization (1:1), open-label, active-controlled, parallel-group comparative study was conducted in 2006-2007 in subjects requiring surgery for asymptomatic impacted mandibular third molar. Ethics committee approval was received prior to study initiation. This study was conducted as per the applicable regulatory guidelines, Indian GCP, and Declaration of Helsinki.

The inclusion criteria were: male and female subjects with age between 18 and 50 years and willingness to provide written informed consent to participate in the study and further follow-up.

Exclusion criteria were: pregnant and breastfeeding women; subjects with known sensitivity to NSAIDs and other drugs; subjects using other NSAIDs; subjects taking psychotropic drugs or other chronic medication; history of blood dyscrasias; immunocompromised patients; individuals suffering from angioedema, urticaria, asthma, or rhinitis; and individuals on antibiotics, except cephalosporines, quinolones, macrolide antibiotics, seratiopeptidase and trypsin or chymotrypsin.

Subjects were not allowed to take any other anti-inflammatory agent or analgesic without consulting one of the study doctors. The trial was set to identify non-inferiority of the piroxicam sublingual tablets as compared to diclofenac oral tablets. A total 100 subjects were selected and randomized to one of the two treatment groups. One group received two sublingual tablets of piroxicam 20 mg [Ugesic, Meyer Organics Pvt. Ltd. (MOPL), India] on the first and second postoperative days, and one tablet on the third postoperative day. The other group received one 50-mg tablet of diclofenac (Voveran™, Novartis India Ltd., India) orally, thrice daily, on the first, second, and third postoperative days. For randomization five blocks were prepared, each consisting of 10 treatment allocation codes (5 × A and 5 × B in random manner). Blocks were generated using Microsoft ® Excel ® and the equal distribution of A and B was ensured in each block. The patient received sublingual piroxicam tablets if the code was 'A' and diclofenac tablets if the code was 'B' in that particular block at the time of randomization. The blocks which were numbered 1-5 were used one after the other to randomize 50 patients. The investigators followed the randomization chart provided by the study sponsor (MOPL).

The main study outcome was reduction in pain. Pain was assessed immediately after surgery and at 15 min, 30 min, 60 min, 6 h, and 12 h on the first day post surgery. Thereafter, extraoral examination was done every 12 hours for assessment of inflammation, trismus, and swelling. The findings were recorded and compared between the two groups. Presence or reduction of swelling was assessed by clinical observation of the patients. Presence or improvement of trismus was evaluated by questioning the patients about the degree of difficulty and pain while opening the mouth, difficulty in eating and swallowing, difficulty in joint mobilization and speech, and overall improvement in the condition.

At the end of the study, we asked the treating physician as well as the patients themselves to give their overall impression regarding the efficacy of the drug used and the tolerability as assessed by incidence of adverse effects. For assessment of pain intensity and pain relief at different time points a 10-cm visual-analog scale (VAS) was used, where 0-2 cm represented 'no pain,' 2.1-4 cm represented 'mild pain,' 4.1-6 cm represented 'moderate pain,' 6.1-8 cm represented 'severe pain,' and 8.1-10 cm represented 'very severe or worst possible pain.'

All anesthetic and surgical procedures were conducted following a standard protocol (Protocol Number MOPL-193-B): anesthetic block of inferior alveolar, lingual, and buccal nerves with 2% lignocaine hydrochloride with adrenaline 1:100000; mucoperiosteal incision (Ward's or modified Ward's incision) with a No. 15 scalpel blade and raising of a mucoperiosteal flap; osteotomy with a rotary instrument at low rotation and under irrigation with 0.9% saline solution; tooth sectioning, when indicated, with a rotary instrument; use of straight and offset elevators to luxate and remove the tooth; alveolus prophylaxis-bone smoothing, irrigation, and removal of follicle; 3-0 black silk simple interrupted sutures, one placed distal to the second molar, a second placed near the distal end of the flap, and the third placed on the anterior releasing incision; and postoperative recommendations. In both the groups, amoxycillin 500 mg thrice daily was given for 5 days.

The data of the two treatment groups was examined by MSTAT ® statistical software. Values were represented as mean ± SD and frequency counts. The paired-t test, Chi-square test, and Fisher's exact test were used to test the significance of findings.


   Results Top


A total of 100 patients with impacted mandibular third molar were enrolled in the study and all underwent oral surgery for removal of the third molar. The patients were randomly assigned to receive one of the two treatment regimens. Forty-eight subjects (32 men and 16 women; mean age: 27.87 ± 7.68) in the study group (sublingual piroxicam) and 45 subjects (24 men and 21 women, mean age 29.29 ± 7.06) in the control group (oral diclofenac) completed the study. Two patients in the piroxicam group and five patients in the control group were lost to follow-up. Data of the 93 patients who completed the study were analyzed to examine the efficacy and safety of the treatment regimens [Figure 1]. There was no significant difference between the two groups in baseline demographic and other characteristics [Table 1]. The pain intensity scores were similar at baseline in both treatment groups. In the piroxicam group there was a 54.66% reduction in pain on the 1 st postoperative day, 54.83% reduction on the 2 nd day, and 51.68% reduction by the 3 rd day (P<.001). In comparison, in the diclofenac group, there was 37.97%, 41.92%, and 30.97% reduction in pain intensity on the 1 st , 2 nd , and 3 rd postoperative days, respectively (P<.01) [Table 2].
Figure 1: Consort diagram

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Table 1: Comparison of baseline characteristics of the two groups

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Table 2: Comparison of pain reduction (VAS score) in the two groups

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The incidence of swelling was higher in the control group [Table 3]. On the 2 nd postoperative day 11% of patients in the control group reported swelling as compared to 6% in the study group (P=.26). None of the patients in the study group reported swelling on the 3 rd postoperative day as compared to 4% in the control group. The incidence of trismus was also higher in the diclofenac group as compared to the piroxicam group (P=.75) [Table 4]. In the piroxicam group no side effects like any gastrointestinal (GI) adverse effects were seen, whereas in the diclofenac group five patients (11%) reported GI disturbances.
Table 3: Comparison of presence of swelling in the two groups

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Table 4: Comparison of presence of trismus in the two groups

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Overall efficacy of both the study drugs was graded by the physician as excellent, good, fair and poor/no effect. In the piroxicam group, 8% were graded as excellent and 90% as good. On the other hand, in the diclofenac sodium group 89% were graded as good and 11% were graded as fair. This assessment data was significantly better (P=.035) for piroxicam group. Also, the overall assessment by the patients showed better efficacy for the piroxicam group (P=.013) [Table 5].
Table 5: Global assessment of efficacy

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   Discussion Top


Acute pain serves an alarm function, and the inflammatory process is a prerequisite for normal tissue healing. However, pain and other inflammatory reactions may often overshoot their goal and cause unnecessary sequelae. The magnitude of postoperative pain depends on the degree of tissue damage and on the extent of operative trauma. Reducing pain and excessive inflammatory reactions is necessary not just for immediate reduction of postoperative morbidity, but also to provide prolonged benefits by preventing further worsening of pathologic states. An understanding of the pathophysiology of pain and the inflammatory process is essential for adequate management of postoperative sequelae. [18]

Surgical trauma activates a biochemical cascade, with the synthesis or release of prostaglandins, bradykinin, substance-P, histamine, and other substances. They interact to produce plasma extravasation, leading to edema. They also excite and sensitize peripheral nerve endings, resulting in the clinical manifestation of hyperalgesia. These substances have several other effects on peripheral nerve endings. They stimulate the release of neuropeptides such as calcitonin gene-related peptide (CGRP) from peripheral nerve endings, contributing to the synergistic effects of other biochemical cascades. These substances form a positive feedback loop that is thought to continually refuel the inflammatory process, maintaining the clinical signs of inflammation for days after the initial stimulus. [10]

This was the first study of its type designed and conducted to compare the analgesic effect of sublingual piroxicam against the established NSAID diclofenac in patients undergoing extraction of impacted mandibular third molars. Earlier clinical trials [19],[20],[21],[22] that have examined pain after removal of third molars have compared the analgesic effect of other NSAIDs with placebos or aspirin or compared effect of sublingual piroxicam with placebo or aspirin.

In this study, there was a statistically significant reduction in pain on the 1 st , 2 nd , and 3 rd postoperative days in the piroxicam group. No rescue treatment was required by any of the subjects in both the groups during the trial. Thus, sublingual piroxicam was effective in the management of postoperative pain following surgical removal of mandibular impacted third molar. A sublingually administered drug is absorbed across the oral mucosa and thus avoids gastrointestinal and/or hepatic degradation prior to entry into the systemic circulation. Sublingual formulations are therefore considered more effective than oral ones. The sublingual dosage form of piroxicam used in this study showed no adverse effects, whereas oral diclofenac was associated with GI disturbances (11%) like nausea, vomiting, and gastritis. The most frequently reported GI disturbances with diclofenac or any NSAID are abdominal pain, constipation, diarrhea, and GI ulcers. Other clinical benefits associated with this quick-dissolving formulation of piroxicam include: ease of use, (once daily dose) which ensures better and improved patient compliance; self-administration, which renders it useful in general practice and outpatients; and fast effect because of quick onset of action.


   Conclusion Top


Sublingual dosage forms of NSAIDs are more effective and have less GI adverse effects than oral dosage forms. Sublingual piroxicam (two 20-mg tablets given once daily) had better efficacy and tolerability profile than 150 mg diclofenac (50 mg tablet given orally thrice daily) in the management of pain after surgical removal of impacted mandibular third molar. Ease of use and the quick action of this formulation are advantages that are likely to improve patient compliance.

 
   References Top

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13.Schultze MS, Schmelzeisen R, Frolich JC, Schmele H. Use of Ibuprofen and methyl prednisolone for prevention of Pain and swelling after removal of Impacted third molars. J Oral Maxillofac Surg 1995;53:2-7.  Back to cited text no. 13
    
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15.Supervia A, Pedro-Rotet J, Nogues X, Echarte JL, Mínguez S, Iglesias ML, et al. Piroxicam fast dissolving dosage vs diclofenac sodium in the treatment of acute renal colic: A double-blind controlled trial. Br J Urol 1998;81:27-30.  Back to cited text no. 15
    
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21.Daniels SE, Desjardins PJ, Talwalker S, Recker DP, Verburg KM. The analgesic efficacy of valdecoxib vs. oxycodone/acetaminophen after oral surgery. J Am Dent Assoc 2002;133:611-21.  Back to cited text no. 21
    
22.Hersh EV, Cooper S, Betts N, Wedell D, MacAfee K, Quinn P, et al. Single dose and multimode analgesic study of ibuprofen and meclofenamate sodium after third molar surgery. Oral Surg Oral Med Oral Pathol 1993;76:680-7.  Back to cited text no. 22
    

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Correspondence Address:
Himanshu P Tayade
Meyer Organics Pvt. Ltd
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0970-9290.111282

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    Figures

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]

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