Skip to main content
SpringerLink
Log in

Topical Ketoprofen Patch

  • Review Article
  • Published:
Drugs in R & D Aims and scope Submit manuscript

Abstract

Although oral nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in the treatment of a variety of acute and chronic pain conditions, their use may be associated with serious systemic adverse effects, particularly gastrointestinal disorders. In order to minimise the incidence of systemic events related to such agents, topical NSAIDs have been developed. Topical NSAIDs, applied as gels, creams or sprays, penetrate the skin, subcutaneous fatty tissue and muscle in amounts that are sufficient to exert a therapeutic effect on peripheral and central mechanisms in the absence of high plasma concentrations. Data indicate that topical NSAIDs are effective at relieving pain in a number of acute and chronic pain indications.

This review article discusses the pharmacokinetics, efficacy and tolerability of a new formulation of ketoprofen available as a topical patch. The topical patch containing ketoprofen 100mg as the active principle has been developed using a novel delivery system that dispenses therapeutic doses of the drug directly to the site of injury.

Pharmacokinetic data indicate that although plasma levels of ketoprofen are higher when the drug is administered as a patch versus a gel, the total systemic bioavailability of ketoprofen 100mg administered via a patch is no more than 10% of that reported for ketoprofen 100mg administered orally. Because the patch facilitates ketoprofen delivery over a 24-hour period, the drug remains continually present in the tissue subjacent to the site of application. High tissue but low plasma ketoprofen concentrations mean that while tissue concentrations are high enough to exert a therapeutic effect, plasma concentrations remain low enough to not result in systemic adverse events caused by elevated serum NSAID levels. Phase III clinical trials in patients with non-articular rheumatism and traumatic painful soft tissue injuries showed that the topical ketoprofen patch was significantly more effective than placebo at reducing pain during daily activities and spontaneous pain after 7 days’ treatment. Moreover, the topical ketoprofen patch was well tolerated; adverse events were primarily cutaneous in nature and occurred in a similar number of ketoprofen and placebo recipients suggesting that these events were related to the patch itself rather than the active ingredient. The incidence of gastrointestinal adverse events was low (<8% of all patients), and occurred in a similar proportion of patients receiving ketoprofen and placebo.

Thus, the topical ketoprofen patch appears to be a simple, effective and safe therapeutic option for the treatment of local painful inflammation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Table I
Table II

Similar content being viewed by others

Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

References

  1. Moore RA, Tramer MR, Carroll D, et al. Quantitative systematic review of topically applied non-steroidal anti-inflammatory drugs. BMJ 1998; 316 (7128): 333–8

    Article  PubMed  CAS  Google Scholar 

  2. McCormack K, Brune K. Dissociation between the antinociceptive and anti-inflammatory effects of the nonsteroidal anti-inflammatory drugs: a survey of their analgesic efficacy. Drugs 1991; 41 (4): 533–47

    Article  PubMed  CAS  Google Scholar 

  3. Bannwarth B, Demotes-Mainard F, Schaeverbeke T, et al. Where are peripheral analgesics acting? Ann Rheum Dis 1993; 52 (1): 1–4

    Article  PubMed  CAS  Google Scholar 

  4. Cashman JN. The mechanisms of action of NSAIDs in analgesia. Drugs 1996; 52 Suppl. 5: 13–23

    Article  PubMed  CAS  Google Scholar 

  5. Wynne HA, Campbell M. Pharmacoeconomics of nonsteroidal anti-inflammatory drugs (NSAIDs). Pharmacoeconomics 1993; 3 (2): 107–23

    Article  PubMed  CAS  Google Scholar 

  6. Heyneman CA, Lawless-Liday C, Wall GC. Oral versus topical NSAIDs in rheumatic diseases: a comparison. Drugs 2000; 60 (3): 555–74

    Article  PubMed  CAS  Google Scholar 

  7. Grahame R. Transdermal non-steroidal anti-inflammatory agents. Br J Clin Pract 1995; 49 (1): 33–5

    PubMed  CAS  Google Scholar 

  8. Mason L, Moore RA, Edwards JE, et al. Topical NSAIDs for acute pain: a meta-analysis. BMC Fam Pract 2004; 5 (1): 10

    Article  PubMed  Google Scholar 

  9. Rolf C, Movin T, Engstrom B, et al. An open, randomized study of ketoprofen in patients in surgery for Achilles or patellar tendinopathy. J Rheumatol 1997; 24 (8): 1595–8

    PubMed  CAS  Google Scholar 

  10. Rolf C, Engstrom B, Beauchard C, et al. Intra-articular absorption and distribution of ketoprofen after topical plaster application and oral intake in 100 patients undergoing knee arthroscopy. Rheumatology (Oxford) 1999; 38 (6): 564–7

    Article  CAS  Google Scholar 

  11. Jokhio IA, Siddiqui KA, Waraich T, et al. Study of efficacy and tolerance of ketoprofen and diclofenac sodium in the treatment of acute rheumatic and traumatic conditions. J Pak Med Assoc 1998; 48 (12): 373–6

    PubMed  CAS  Google Scholar 

  12. Patel RK, Leswell PF. Comparison of ketoprofen, piroxicam, and diclofenac gels in the treatment of acute soft-tissue injury in general practice. General Practice Study Group. Clin Ther 1996; 18 (3): 497–507

    Article  PubMed  CAS  Google Scholar 

  13. Orudis (ketoprofen) Prescribing Information. Wyeth 2003

    Google Scholar 

  14. Cordero JA, Camacho M, Obach R, et al. In vitro based index of topical anti-inflammatory activity to compare a series of NSAIDs. Eur J Pharm Biopharm 2001; 51 (2): 135–42

    Article  PubMed  CAS  Google Scholar 

  15. Cordero JA, Alarcon L, Escribano E, et al. A comparative study of the transdermal penetration of a series of nonsteroidal antiinflammatory drugs. J Pharm Sci 1997; 86 (4): 503–8

    Article  PubMed  CAS  Google Scholar 

  16. Flouvat B, Roux A, Delhotal-Landes B. Pharmacokinetics of ketoprofen in man after repeated percutaneous administration. Arzneimittel Forschung 1989; 39 (7): 812–5

    PubMed  CAS  Google Scholar 

  17. Cannavino CR, Abrams J, Palinkas LA, et al. Efficacy of transdermal ketoprofen for delayed onset muscle soreness. Clin J Sport Med 2003; 13 (4): 200–8

    Article  Google Scholar 

  18. Rovati LC, Setnikar I, Genazzani AR. Dose-response efficacy of a new estradiol transdermal matrix patch for 7-day application: a randomized, double-blind, placebo-controlled study. Italian Menopause Research Group. Gynecol Endocrinol 2000; 14 (4): 282–91

    Article  PubMed  CAS  Google Scholar 

  19. Notelovitz M, Cassel D, Hille D, et al. Efficacy of continuous sequential transdermal estradiol and norethindrone acetate in relieving vasomotor symptoms associated with menopause. Am J Obstet Gynecol 2000; 182 (1 Pt 1): 7–12

    Article  PubMed  CAS  Google Scholar 

  20. Zieman M, Guillebaud J, Weisberg E, et al. Contraceptive efficacy and cycle control with the Ortho Evra/Evra transdermal system: the analysis of pooled data. Fertil Steril 2002; 77 (2 Suppl. 2): S13–8

    Article  Google Scholar 

  21. Audet MC, Moreau M, Koltun WD, et al. Evaluation of contraceptive efficacy and cycle control of a transdermal contraceptive patch vs an oral contraceptive: a randomized controlled trial. JAMA 2001; 285 (18): 2347–54

    Article  PubMed  CAS  Google Scholar 

  22. Palmer KJ, Buckley MM, Faulds D. Transdermal nicotine: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy as an aid to smoking cessation. Drugs 1992; 44 (3): 498–529

    Article  PubMed  CAS  Google Scholar 

  23. Hays JT, Croghan IT, Schroeder DR, et al. Over-the-counter nicotine patch therapy for smoking cessation: results from randomized, double-blind, placebo-controlled, and open label trials. Am J Public Health 1999; 89 (11): 1701–7

    Article  PubMed  CAS  Google Scholar 

  24. Tonnesen P, Paoletti P, Gustavsson G, et al. Higher dosage nicotine patches increase one-year smoking cessation rates: results from the European CEASE trial. Collaborative European Anti-Smoking Evaluation. European Respiratory Society. Eur Respir J 1999; 13 (2): 238–46

    Article  PubMed  CAS  Google Scholar 

  25. Allan L, Hays H, Jensen NH, et al. Randomised crossover trial of transdermal fentanyl and sustained release oral morphine for treating chronic non-cancer pain. BMJ 2001; 322 (7295): 1154–8

    Article  PubMed  CAS  Google Scholar 

  26. Mystakidou K, Befon S, Kouskouni E, et al. From codeine to transdermal fentanyl for cancer pain control: a safety and efficacy clinical trial. Anticancer Res 2001; 21 (3C): 2225–30

    PubMed  CAS  Google Scholar 

  27. Mertin D, Cordes G, Heiling T. Ketoprofen TDS, a new approach for the therapy of rheumatism and sport injuries [abstract]. Proceedings of the 2nd World Meeting APGI/APV; 1998 May 25–28; Paris, France. 893–4

    Google Scholar 

  28. Klaffenbach P, Vollmer U. In vitro percutaneous absorption in isolated skin: test-product ketoprofen TDS patch in comparison with ketoprofen gel. Report on file September 2000

    Google Scholar 

  29. Osterwalder A, Reiner V, Reiner G, et al. Tissue absorption and distribution of ketoprofen after patch application in subjects undergoing knee arthroscopy or endoscopic carpal ligament release. Arzneimittel Forschung 2002; 52 (11): 822–7

    PubMed  CAS  Google Scholar 

  30. Crestani S, Ismaili S. IPAS-KETO/TDS-280-01, Final report: systemic bioavailability study of ketoprofen administered to healthy volunteers as TDS patch (test formulation) vs gel (reference formulation). Report on file June 2002

    Google Scholar 

  31. Verbeeck RK, Corman CL, Wallace SM, et al. Single and multiple dose pharmacokinetics of enteric coated ketoprofen: effect of cimetidine. Eur J Clin Pharmacol 1988; 35 (5): 521–7

    Article  PubMed  CAS  Google Scholar 

  32. Data on file, Zambon Group, Bresso, Italy

  33. Mazieres B, Rouanet S, Guillon Y, et al. Topical ketoprofen patch in the treatment of tendinitis: a randomized, double blind, placebo controlled study. J Rheumatol 2005; 32: 1563–70

    PubMed  CAS  Google Scholar 

  34. Hrobjartsson A, Gotzsche PC. Is the placebo powerless? An analysis of clinical trials comparing placebo with no treatment. N Engl J Med 2001; 344 (21): 1594–602

    Article  PubMed  CAS  Google Scholar 

  35. Mazieres B, Rouanet S, Velicy J, et al. Topical ketoprofen patch (100mg) in the treatment of ankle sprain: a randomized, double-blind, placebo-controlled study. Am J Sports Med 2005; 33: 515–23

    Article  PubMed  Google Scholar 

  36. Lee JS, Hobden E, Stiell IG, et al. Clinically important change in the visual analog scale after adequate pain control. Acad Emerg Med 2003; 10 (10): 1128–30

    Article  PubMed  Google Scholar 

  37. Cepeda MS, Africano JM, Polo R, et al. What decline in pain intensity is meaningful to patients with acute pain? Pain 2003; 105 (1–2): 151–7

    Article  PubMed  Google Scholar 

  38. US Food and Drug Administration. Guidelines for the clinical value of analgesic drugs. 1992

    Google Scholar 

  39. Dionne RA, Gordon SM, Tahara M, et al. Analgesic efficacy and pharmacokinetics of ketoprofen administered into a surgical site. J Clin Pharmacol 1999; 39 (2): 131–8

    Article  PubMed  CAS  Google Scholar 

  40. Patel RK, Leswell PF. Comparison of ketoprofen, piroxicam, and diclofenac gels in the treatment of acute soft-tissue injury in general practice. Clin Ther 1996; 18 (3): 497–507

    Article  PubMed  CAS  Google Scholar 

  41. Airaksinen O, Venalainen J, Pietilainen T. Ketoprofen 2.5% gel versus placebo gel in the treatment of acute soft tissue injuries. Int J Clin Pharmacol Ther Toxicol 1993; 31 (11): 561–3

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

No external funding was provided for this study. BM was the principal investigator for two trials of topical ketoprofen patch referred to in this review and received fees for writing the protocols, participating in the blind reviews, supervising the final reports and writing the two papers. BM has also undertaken educational activities with the Zambon Group, but is totally independent of the company and declares no conflict of interest.

Author information

Authors and Affiliations

  1. Service de Rhumatologie, CHU Rangueil, Avenue Jean Poulhes, 1, TSA, 50032 31059, Toulouse Cedex 9, France

    Bernard Mazières

Authors
  1. Bernard Mazières
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bernard Mazières.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mazières, B. Topical Ketoprofen Patch. Drugs in R D 6, 337–344 (2005). https://doi.org/10.2165/00126839-200506060-00003

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00126839-200506060-00003

Keywords

Search

Navigation