Download PDF
Int J Sports Med 2011; 32(8): 635-643
DOI: 10.1055/s-0031-1275359
Clinical Sciences

© Georg Thieme Verlag KG Stuttgart · New York

Analgesic Efficacy and Safety of the Diclofenac Epolamine Topical Patch 1.3% (DETP) in Minor Soft Tissue Injury

K. Kuehl1 , W. Carr2 , J. Yanchick3 , M. Magelli4 , S. Rovati5
  • 1Oregon Health & Science University, Division of Health Promotion & Sports Medicine, OR, Portland, United States
  • 2Leslie Surgery, Leslie, United Kingdom
  • 3Alpharma Pharmaceuticals, a wholly owned subsidiary of King Pharmaceuticals®, Inc., Bridgewater, NJ, United States
  • 4GTx, Inc, Medical Affairs, Memphis, TN, United States
  • 5Institut Biochimique SA, Research and Development, Pambio-Noranco, Switzerland
Further Information

Publication History

accepted after revision February 28, 2011

Publication Date:
11 May 2011 (online)

Also available at
    Permissions and Reprints

Abstract

The diclofenac epolamine topical patch 1.3% was designed to deliver analgesic concentrations of diclofenac to an underlying soft tissue injury site, while limiting systemic exposure to diclofenac. This randomized, double-blind, placebo-controlled study evaluated the safety and efficacy of the diclofenac epolamine topical patch for the treatment of acute pain due to minor soft tissue injury. Patients (18–65 years, inclusive) with clinically significant minor soft tissue injuries (mild or moderate sprain, strain, or contusion) incurred within 7 days of study entry and having pain scores ≥5 on a Visual Analog Scale of 0–10 were enrolled. Patients were randomized to receive the diclofenac epolamine topical patch (n=207) or placebo patch (n=211) application twice daily for 14 days or until pain resolution. Patients recorded pain scores every 12 h at the time of patch removal using the Visual Analog Scale. Investigator-assessed global response to therapy was also evaluated. Safety data were collected throughout the study. Twice-daily treatment with diclofenac epolamine topical patch produced a statistically significant reduction in mean pain score relative to baseline by an additional 18.2% in the diclofenac epolamine topical patch group (0.435±0.268) compared with the placebo group (0.532±0.293) (p=0.002; overall) beginning after application of the second patch. Consistent with this treatment effect, median time to pain resolution was shortened by 2 days in the diclofenac epolamine topical patch group relative to the placebo group (p=0.007). These results were reinforced independently by investigators who reported treatment as good or excellent for 58% of diclofenac epolamine topical patch-treated patients compared with 49% in the placebo patch group (p=0.008). The most common adverse events were treatment site related (n=16, 7.9% diclofenac epolamine topical patch; n=12, 5.8% placebo patch). Most (80%) patients reported tolerability as excellent or good. In conclusion, the diclofenac epolamine topical patch provides effective, rapid pain relief for the treatment of acute pain from minor soft tissue injury and appears generally safe and well tolerated.

Key words

acute pain treatment - clinical trial - diclofenac topical patch - musculoskeletal injury - NSAID

References

  • 1 Assandri A, Canali S, Giachetti C. Local tolerability and pharmacokinetic profile of a new transdermal delivery system, diclofenac hydroxyethylpyrrolidine plaster.  Drugs Exp Clin Res. 1993;  19 89-95
    PubMedGoogle Scholar
  • 2 Bertin P, Behier JM, Noel E, Leroux JL. Celecoxib is as efficacious as naproxen in the management of acute shoulder pain.  J Int Med Res. 2003;  31 102-112
    PubMedGoogle Scholar
  • 3 Bijur PE, Silver W, Gallagher EJ. Reliability of the visual analog scale for measurement of acute pain.  Acad Emerg Med. 2001;  8 1153-1157
    CrossrefPubMedGoogle Scholar
  • 4 Bruhlmann P, de Vathaire F, Dreiser RL, Michel BA. Short-term treatment with topical diclofenac epolamine plaster in patients with symptomatic knee osteoarthritis: pooled analysis of two randomised clinical studies.  Curr Med Res Opin. 2006;  22 2429-2438
    CrossrefPubMedGoogle Scholar
  • 5 Cannon CP, Curtis SP, Bolognese JA, Laine L. Clinical trial design and patient demographics of the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) study program: cardiovascular outcomes with etoricoxib versus diclofenac in patients with osteoarthritis and rheumatoid arthritis.  Am Heart J. 2006;  152 237-245
    CrossrefPubMedGoogle Scholar
  • 6 Cannon CP, Curtis SP, FitzGerald GA, Krum H, Kaur A, Bolognese JA, Reicin AS, Bombardier C, Weinblatt ME, van der Heijde D, Erdmann E, Laine L. Cardiovascular outcomes with etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme: a randomised comparison.  Lancet. 2006;  368 1771-1781
    CrossrefPubMedGoogle Scholar
  • 7 Capone ML, Sciulli MG, Tacconelli S, Grana M, Ricciotti E, Renda G, Di Gregorio P, Merciaro G, Patrignani P. Pharmacodynamic interaction of naproxen with low-dose aspirin in healthy subjects.  J Am Coll Cardiol. 2005;  45 1295-1301
    CrossrefPubMedGoogle Scholar
  • 8 Catella-Lawson F, Reilly MP, Kapoor SC, Cucchiara AJ, DeMarco S, Tournier B, Vyas SN, FitzGerald GA. Cyclooxygenase inhibitors and the antiplatelet effects of aspirin.  N Engl J Med. 2001;  345 1809-1817
    CrossrefPubMedGoogle Scholar
  • 9 Centers for Disease Control and Prevention . Nonfatal sports- and recreation-related injuries treated in emergency departments.  MMWR. 2002;  51 736-740
    PubMedGoogle Scholar
  • 10 Dreiser RL, Tisne-Camus M. DHEP plasters as a topical treatment of knee osteoarthritis – a double-blind placebo-controlled study.  Drugs Exp Clin Res. 1993;  19 117-123
    PubMedGoogle Scholar
  • 11 Ekman EF, Fiechtner JJ, Levy S, Fort JG. Efficacy of celecoxib versus ibuprofen in the treatment of acute pain: a multicenter, double-blind, randomized controlled trial in acute ankle sprain.  Am J Orthop. 2002;  31 445-451
    PubMedGoogle Scholar
  • 12 Emery P, Koncz T, Pan S, Lowry S. Analgesic effectiveness of celecoxib and diclofenac in patients with osteoarthritis of the hip requiring joint replacement surgery: a 12-week, multicenter, randomized, double-blind, parallel-group, double-dummy, noninferiority study.  Clin Ther. 2008;  30 70-83
    CrossrefPubMedGoogle Scholar
  • 13 Evans JM, McMahon AD, McGilchrist MM, White G, Murray FE, McDevitt DG, MacDonald TM. Topical non-steroidal anti-inflammatory drugs and admission to hospital for upper gastrointestinal bleeding and perforation: a record linkage case-control study.  BMJ. 1995;  311 22-26
    CrossrefPubMedGoogle Scholar
  • 14 Fini A, Fazio G, Rapaport I. Diclofenac/N-(2-hydroxyethyl)pyrrolidine:a new salt for an old drug.  Drugs Exp Clin Res. 1993;  19 81-88
    PubMedGoogle Scholar
  • 15 Gallacchi G, Marcolongo R. Pharmacokinetics of diclofenac hydroxyethylpyrrolidine (DHEP) plasters in patients with monolateral knee joint effusion.  Drugs Exp Clin Res. 1993;  19 95-97
    PubMedGoogle Scholar
  • 16 Goldstein JL, Lowry SC, Lanza FL, Schwartz HI, Dodge WE. The impact of low-dose aspirin on endoscopic gastric and duodenal ulcer rates in users of a non-selective non-steroidal anti-inflammatory drug or a cyclo-oxygenase-2-selective inhibitor.  Aliment Pharmacol Ther. 2006;  23 1489-1498
    CrossrefPubMedGoogle Scholar
  • 17 Green GA. Understanding NSAIDs: from aspirin to COX-2.  Clin Cornerstone. 2001;  3 50-60
    CrossrefPubMedGoogle Scholar
  • 18 Harriss DJ, Atkinson G. International Journal of Sports Medicine – ethical standards in sport and exercise science research.  Int J Sports Med. 2009;  30 701-702
    Google Scholar
  • 19 Haroutiunian S, Drennan DA, Lipman AG. Topical NSAID therapy for musculoskeletal pain.  Pain Med. 2010;  11 535-549
    CrossrefPubMedGoogle Scholar
  • 20 Jenoure PJ, Rostan A, Germion G. Multicenter, double-blind, controlled clinical study on diclofenac Tissugel plaster in patients with epicondylitis.  Med Sport. 1997;  50 285-292
    PubMedGoogle Scholar
  • 21 Joussellin E. Flector Tissugel® dans le traitement des entorses douloureuses de la cheville [Flector Tissugel® in the treatment of painful ankle sprain].  J Traumatol Sport. 2003;  20 1S5-1S9
    PubMedGoogle Scholar
  • 22 Kampfer H, Brautigam L, Geisslinger G, Pfeilschifter J, Frank S. Cyclooxygenase-1-coupled prostaglandin biosynthesis constitutes an essential prerequisite for skin repair.  J Invest Dermatol. 2003;  120 880-890
    CrossrefPubMedGoogle Scholar
  • 23 Katz J, Jackson M, Kavanagh BP, Sandler AN. Acute pain after thoracic surgery predicts long-term post-thoracotomy pain.  Clin J Pain. 1996;  12 50-55
    CrossrefPubMedGoogle Scholar
  • 24 Kearney PM, Baigent C, Godwin J, Halls H, Emberson JR, Patrono C. Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials.  BMJ. 2006;  332 1302-1308
    CrossrefPubMedGoogle Scholar
  • 25 Lin J, Zhang W, Jones A, Doherty M. Efficacy of topical non-steroidal anti-inflammatory drugs in the treatment of osteoarthritis: meta-analysis of randomised controlled trials.  BMJ. 2004;  329 324
    CrossrefPubMedGoogle Scholar
  • 26 Mason L, Moore RA, Edwards JE, Derry S, McQuay HJ. Topical NSAIDs for acute pain: a meta-analysis.  BMC Fam Pract. 2004;  5 10
    CrossrefPubMedGoogle Scholar
  • 27 Mason L, Moore RA, Edwards JE, Derry S, McQuay HJ. Topical NSAIDs for chronic musculoskeletal pain: systematic review and meta-analysis.  BMC Musculoskelet Disord. 2004;  5 28
    CrossrefPubMedGoogle Scholar
  • 28 McCarberg BH, Argoff CE. Topical diclofenac epolamine patch 1.3 % for treatment of acute pain caused by soft tissue injury.  Int J Clin Pract. 2010;  64 1546-1553
    CrossrefPubMedGoogle Scholar
  • 29 Moore RA, Tramer MR, Carroll D, Wiffen PJ, McQuay HJ. Quantitative systematic review of topically applied non-steroidal anti-inflammatory drugs.  BMJ. 1998;  316 333-338
    CrossrefPubMedGoogle Scholar
  • 30 Mueller EA, Kirch W, Reiter S. Extent and time course of pain intensity upon treatment with a topical diclofenac sodium patch versus placebo in acute traumatic injury based on a validated end point: post hoc analysis of a randomized placebo-controlled trial.  Expert Opin Pharmacother. 2010;  11 493-498
    CrossrefPubMedGoogle Scholar
  • 31 National Centers for Health Statistics . Chartbook on Trends in the Health of Americans 2006.  Special Feature: Pain. 2006; 
    PubMedGoogle Scholar
  • 32 Ouellet M, Riendeau D, Percival MD. A high level of cyclooxygenase-2 inhibitor selectivity is associated with a reduced interference of platelet cyclooxygenase-1 inactivation by aspirin.  Proc Natl Acad Sci USA. 2001;  98 14583-14588
    CrossrefPubMedGoogle Scholar
  • 33 Page J, Henry D. Consumption of NSAIDs and the development of congestive heart failure in elderly patients: an underrecognized public health problem.  Arch Intern Med. 2000;  160 777-784
    CrossrefPubMedGoogle Scholar
  • 34 Perttunen K, Tasmuth T, Kalso E. Chronic pain after thoracic surgery: a follow-up study.  Acta Anaesthesiol Scand. 1999;  43 563-567
    CrossrefPubMedGoogle Scholar
  • 35 Petersen B, Rovati S. Diclofenac epolamine (Flector) patch: evidence for topical activity.  Clin Drug Investig. 2009;  29 1-9
    PubMedGoogle Scholar
  • 36 Petrella R, Ekman EF, Schuller R, Fort JG. Efficacy of celecoxib, a COX-2-specific inhibitor, and naproxen in the management of acute ankle sprain: results of a double-blind, randomized controlled trial.  Clin J Sport Med. 2004;  14 225-231
    CrossrefPubMedGoogle Scholar
  • 37 Petri M, Hufman SL, Waser G, Cui H, Snabes MC, Verburg KM. Celecoxib effectively treats patients with acute shoulder tendinitis/bursitis.  J Rheumatol. 2004;  31 1614-1620
    PubMedGoogle Scholar
  • 38 Poobalan AS, Bruce J, King PM, Chambers WA, Krukowski ZH, Smith WC. Chronic pain and quality of life following open inguinal hernia repair.  Br J Surg. 2001;  88 1122-1126
    CrossrefPubMedGoogle Scholar
  • 39 Predel HG, Koll R, Pabst H, Dieter R, Gallacchi G, Giannetti B, Bulitta M, Heidecker JL, Mueller EA. Diclofenac patch for topical treatment of acute impact injuries: a randomised, double blind, placebo controlled, multicentre study.  Br J Sports Med. 2004;  38 318-323
    CrossrefPubMedGoogle Scholar
  • 40 Rainsford KD, Kean WF, Ehrlich GE. Review of the pharmaceutical properties and clinical effects of the topical NSAID formulation, diclofenac epolamine.  Curr Med Res Opin. 2008;  24 2967-2992
    CrossrefPubMedGoogle Scholar
  • 41 Renda G, Tacconelli S, Capone ML, Sacchetta D, Santarelli F, Sciulli MG, Zimarino M, Grana M, D’Amelio E, Zurro M, Price TS, Patrono C, De Caterina R, Patrignani P. Celecoxib, ibuprofen, and the antiplatelet effect of aspirin in patients with osteoarthritis and ischemic heart disease.  Clin Pharmacol Ther. 2006;  80 264-274
    CrossrefPubMedGoogle Scholar
  • 42 Rowbotham MC, Galer BS, Block JA, Backonja MM. Flector Tissugel®: efficacité et tolérance dans le traitement des microtraumatismes sportifs. Données d’une étude contrôlée conduite aux Etats-Unis [Flector Tissugel®: efficacy and safety in the treatment of minor sports injuries. Data from a controlled trial in the United States].  J Traumatol Sport. 2003;  20 1S15-11S20
    PubMedGoogle Scholar
  • 43 Saillant G. Étude comparant l’efficacité et la tolérance de Flector Tissugel® à celles d’un placebo dans le traitement des entorses bénignes de la cheville. [Study comparing the efficacy and tolerance of Flector Tissugel® to that of a placebo in the treatment of benign ankle sprains].  Medicine du Sport. 1998;  72 1-5
    PubMedGoogle Scholar
  • 44 Sopena F, Lanas A. How to advise aspirin use in patients who need NSAIDs.  Curr Pharm Des. 2007;  13 2248-2260
    CrossrefPubMedGoogle Scholar
  • 45 Vaile JH, Davis P. Topical NSAIDs for musculoskeletal conditions. A review of the literature.  Drugs. 1998;  56 783-799
    CrossrefPubMedGoogle Scholar
  • 46 Vane JR. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs.  Nat New Biol. 1971;  231 232-235
    CrossrefPubMedGoogle Scholar
  • 47 Wolfe MM, Lichtenstein DR, Singh G. Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs.  N Engl J Med. 1999;  340 1888-1899
    CrossrefPubMedGoogle Scholar
  • 48 Yanchick J, Magelli M, Bodie J, Sjogren J, Rovati S. Time to significant pain reduction following DETP application vs. placebo for acute soft tissue injuries.  Curr Med Res Opin. 2010;  26 1993-2002
    CrossrefPubMedGoogle Scholar
  • 49 Zakrzewski PA, O’Donnell HL, Lam WC. Oral versus topical diclofenac for pain prevention during panretinal photocoagulation.  Ophthalmology. 2009;  116 1168-1174
    CrossrefPubMedGoogle Scholar

Correspondence

Dr. Kerry KuehlMD 

Oregon Health & Science

University

Division of Health Promotion &

Sports Medicine

3181 S.W. Sam Jackson Park

Road

CR110

97239-3098 Portland

United States

Phone: + 1/503/494 8051

Fax: + 1/503/494 1310

Email: KuehlK@ohsu.edu

      >