Efficacy and safety profile of combination of tramadol-diclofenac versus tramadol-paracetamol in patients with acute musculoskeletal conditions, postoperative pain, and acute flare of osteoarthritis and rheumatoid arthritis: a Phase III, 5-day open-label study

Ajay S Chandanwale, Subramanian Sundar, Kaliaperumal Latchoumibady, Swati Biswas, Mukesh Gabhane, Manoj Naik, Kamlesh Patel, Ajay S Chandanwale, Subramanian Sundar, Kaliaperumal Latchoumibady, Swati Biswas, Mukesh Gabhane, Manoj Naik, Kamlesh Patel

Abstract

Objective: We aimed to evaluate the safety and efficacy of a fixed-dose combination (FDC) of tramadol and diclofenac versus a standard approved FDC of tramadol and paracetamol, in patients with acute moderate to severe pain.

Methods: A total of 204 patients with moderate to severe pain due to acute musculoskeletal conditions (n=52), acute flare of osteoarthritis (n=52), acute flare of rheumatoid arthritis (n=50), or postoperative pain (n=50) were enrolled in the study at baseline. Each disease category was then randomized to receive either of two treatments for 5 days: group A received an FDC of immediate-release tramadol hydrochloride (50 mg) and sustained-release diclofenac sodium (75 mg) (one tablet, twice daily), and group B received an FDC of tramadol hydrochloride (37.5 mg) and paracetamol (325 mg) (two tablets every 4-6 hours, up to a maximum of eight tablets daily). The primary efficacy end points were reductions in pain intensity from baseline at day 3 and day 5 as assessed by a Visual Analog Scale (VAS) score.

Results: Group A showed a significant reduction in the VAS score for overall pain from baseline on day 3 (P=0.001) and day 5 (P<0.0001) as compared with group B. The combination of tramadol-diclofenac resulted in few mild to moderate adverse events (nausea, vomiting, epigastric pain, and gastritis), which required minimal management, without any treatment discontinuation. The number of adverse events in group A was nine (8.82%) compared with 22 (21.78%) in group B, after 5 days of treatment.

Conclusion: An FDC of tramadol-diclofenac showed a significantly greater reduction in pain intensity and was well tolerated compared with tramadol-paracetamol, resulting in better analgesia in patients suffering from moderate to severe pain due to acute musculoskeletal conditions, postoperative pain following orthopedic surgery, or acute flare of osteoarthritis and rheumatoid arthritis.

Keywords: moderate to severe pain; tramadol and diclofenac combination.

Figures

Figure 1
Figure 1
Comparison of mean VAS score for overall pain, in group A versus group B of the study population. Notes: (A) Mean score for overall pain in AMSP patients. (B) Mean score for overall pain for AFOA patients. (C) Mean score for overall pain in AFRA patients. (D) Mean score for overall pain in POP patients. The blue line is for group A (tramadol + diclofenac) and the red line is for group B (tramadol + paracetamol). Abbreviations: AFOA, acute flare of osteoarthritis; AFRA, acute flare of rheumatoid arthritis; AMSP, acute musculoskeletal pain; POP, postoperative pain; VAS, Visual Analog Scale.

References

    1. Connors AF, Jr, Dawson NV, Desbiens NA, et al. A controlled trial to improve care for seriously ill hospitalized patients. The study to understand prognoses and preferences for outcomes and risks of treatments (SUPPORT). The SUPPORT Principal Investigators. JAMA. 1995;274(20):1591–1598.
    1. Vanderah TW. Pathophysiology of pain. Med Clin North Am. 2007;91(1):1–12.
    1. Rawal N, Macquaire V, Catalá E, Berti M, Costa R, Wietlisbach M. Tramadol/paracetamol combination tablet for postoperative pain following ambulatory hand surgery: a double-blind, double-dummy, randomized, parallel-group trial. J Pain Res. 2011;4:103–110.
    1. Raffa RB. Pharmacology of oral combination analgesics: rational therapy for pain. J Clin Pharm Ther. 2001;26(4):257–264.
    1. [homepage on the Internet] WHO’s cancer pain ladder for adults. World Health Organization; 2012. [Accessed June 27, 2014]. [cited July 28, 2013]. Available from:
    1. Leung L. From ladder to platform: a new concept for pain management. J Prim Health Care. 2012;4(3):254–258.
    1. McCarberg B, Tenzer P. Complexities in the pharmacologic management of osteoarthritis pain. Curr Med Res Opin. 2013;29(5):539–548.
    1. Mercadante S. The use of anti-inflammatory drugs in cancer pain. Cancer Treat Rev. 2001;27(1):51–61.
    1. Schug SA. The role of tramadol in current treatment strategies for musculoskeletal pain. Ther Clin Risk Manag. 2007;3(5):717–723.
    1. Brunton LL, Chabner BA, Knollmann BC. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 12th ed. New York, NY: McGraw Hill; 2011.
    1. Filitz J, Ihmsen H, Günther W, et al. Supra-additive effects of tramadol and acetaminophen in a human pain model. Pain. 2008;136(3):262–270.
    1. McQuay H, Edwards J. Meta-analysis of single dose oral tramadol plus acetaminophen in acute postoperative pain. Eur J Anaesthesiol Suppl. 2003;28:19–22.
    1. Gan TJ. Diclofenac: an update on its mechanism of action and safety profile. Curr Med Res Opin. 2010;26(7):1715–1731.
    1. Raffa RB, Friderichs E, Reimann W, Shank RP, Codd EE, Vaught JL. Opioid and nonopioid components independently contribute to the mechanism of action of tramadol, an ‘atypical’ opioid analgesic. J Pharmacol Exp Ther. 1992;260(1):275–285.
    1. Australian and New Zealand College of Anaesthetists (ANZCA) Acute Pain Management: Scientific Evidence. 2nd ed. Melbourne: Australian and New Zealand College of Anaesthetists; 2005.
    1. Hawker GA, Mian S, Kendzerska T, French M. Measures of adult pain: Visual Analog Scale for Pain (VAS Pain), Numeric Rating Scale for Pain (NRS Pain), McGill Pain Questionnaire (MPQ), Short-Form McGill Pain Questionnaire (SF-MPQ), Chronic Pain Grade Scale (CPGS), Short Form-36 Bodily Pain Scale (SF-36 BPS), and Measure of Intermittent and Constant Osteoarthritis Pain (ICOAP) Arthritis Care Res. 2011;63(S11):S240–S252.
    1. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) [webpage on the internet] American College of Rheu-matology Research Committee; 2012. [Accessed July 23, 2014]. Available from:
    1. IMACS Form 04a: Instructions for the Health Assessment Questionnaire. [Accessed July 23, 2014]. Available from: .
    1. Auad A, Cadena L, Garzón LA, et al. Efficacy and safety of the fixed combination diclofenac/tramadol in acute pain: randomized clinical trial phase III, double-blind, controlled. Iberoamericana Rev Pain. 2009;4:13–23.
    1. Wiffen PJ, Wee B, Moore RA. Oral morphine for cancer pain. Cochrane Database Syst Rev. 2013;7:CD003868.
    1. Mitra S, Khandelwal P, Sehgal A. Diclofenac-tramadol vs diclofenac-acetaminophen combinations for pain relief after caesarean section. Acta Anaesthesiol Scand. 2012;56(6):706–711.
    1. Linares OA, Daly D, Stefanovski D, Boston RC. A new model for using quantitative urine testing as a diagnostic tool for oxycodone treatment and compliance. J Pain Palliat Care Pharmacother. 2013;27(3):244–254.
    1. Pavelka K, Pelisková Z, Stehlíková H, Ratcliffe S, Repas C. Intraindividual differences in pain relief and functional improvement in osteoarthritis with diclofenac or tramadol. Clin Drug Investig. 1998;16(6):421–429.
    1. European Medicines Agency . New safety advice for diclofenac – CMDh endorses PRAC recommendation [press release] London: European Medicines Agency; Jun 28, 2013. [Accessed March 25, 2014]. Available from: .
    1. [homepage on the Internet] SPC. Diclofenac potassium 50 mg tablets. electronic Medicines Compendium (eMC) (Datapharm) 2011. [Accessed June 27, 2014]. [updated January 17, 2014; cited June 19, 2014]. Available from: .

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