Drugs

, Volume 61, Issue 9, pp 1351–1378 | Cite as

Aceclofenac

A Reappraisal of its Use in the Management of Pain and Rheumatic Disease
  • Mukta Dooley
  • Caroline M. Spencer
  • Christopher J. Dunn
Adis Drug Evaluation

Summary

Abstract

Aceclofenac is an orally administered phenylacetic acid derivative with effects on a variety of inflammatory mediators. Through its analgesic and anti-inflammatory properties, aceclofenac provides symptomatic relief in a variety of painful conditions. In patients with osteoarthritis of the knee, the drug decreases pain, reduces disease severity and improves the functional capacity of the knee to a similar extent to diclofenac, piroxicam and naproxen. Aceclofenac reduces joint inflammation, pain intensity and the duration of morning stiffness in patients with rheumatoid arthritis, and is similar in efficacy to ketoprofen, diclofenac, indomethacin and tenoxicam in these patients.

The duration of morning stiffness and pain intensity are reduced, and spinal mobility improved, by aceclofenac in patients with ankylosing spondylitis, with improvements being similar to those observed with indomethacin, naproxen or tenoxicam. Aceclofenac is also effective in other painful conditions (e.g. dental and gynaecological). In contrast to some other NSAIDs, aceclofenac has shown stimulatory effects on cartilage matrix synthesis.

Aceclofenac is well tolerated, with most adverse events being minor and reversible, and affecting mainly the GI system. Although the incidence of GI adverse events with aceclofenac was similar to those of comparator NSAIDs in individual clinical trials, withdrawal rates due to these events were significantly lower with aceclofenac than with ketoprofen and tenoxicam. Superior overall and/or GI tolerability of the drug relative to other NSAIDs has been indicated by a nonrandomised comparison with sustained release diclofenac in 10 142 patients, a meta-analysis of 13 comparisons with diclofenac, naproxen, piroxicam, indomethacin, tenoxicam or ketoprofen in 3574 patients, and preliminary details of a comparison with 10 other NSAIDs in 142 776 patients. Further analysis of the above meta-analytical data has indicated that costs incurred as a result of adverse event management are lower with aceclofenac than with a range of comparator NSAIDs.

Conclusions: Trials of 2 to 6 months’ duration have shown aceclofenac to be an effective agent in the management of pain and rheumatic disease. Data from in vitro studies indicate properties of particular interest with respect to cartilage matrix effects and selectivity for cyclo-oxygenase-2. Aceclofenac is well tolerated, with encouraging reports of improved general and GI tolerability relative to other NSAIDs from a meta-analysis of double-blind trials and from large non-blind studies.

Overview of Pharmacodynamic Properties

Aceclofenac has been shown to exert effects on a variety of mediators of inflammation. The drug inhibits synthesis of the inflammatory cytokines interleukin (IL)-1β and tumour necrosis factor, and inhibits prostaglandin E2 (PGE2) production. Effects on cell adhesion molecules from neutrophils have also been noted. Aceclofenac did not affect IL-6 synthesis in 1 ex vivo study, but significantly decreased basal and IL-1β-stimulated production of this mediator in human chondrocytes in vitro. In another ex vivo study, aceclofenac did not affect the production of leukotriene B4, but a decrease in the stimulated production of reactive oxygen species was observed after 15 (but not 180) days of treatment with aceclofenac 100mg twice daily. The inhibitory effects of aceclofenac on synovial levels of PGE2 have been confirmed in patients with acute knee pain and synovial fluid effusions. In vitro data indicate inhibition of cyclo-oxygenase (COX)-1 and -2 by aceclofenac in whole blood assays, with selectivity for COX-2 being evident.

In contrast to some other NSAIDs, aceclofenac has shown stimulatory effects on cartilage matrix synthesis that may be linked to the ability of the drug to inhibit IL-1β activity. In vitro data indicate stimulation by the drug of synthesis of glycosaminoglycan in osteoarthritic cartilage. There is also evidence that aceclofenac stimulates the synthesis of IL-1 receptor antagonist in human articular chondrocytes subjected to inflammatory stimuli, and that 4′-hydroxyaceclofenac has chondroprotective properties attributable to suppression of IL-1β-mediated promatrix metalloproteinase production and proteoglycan release.

In studies in rodents, aceclofenac alleviated induced pain and hyperthermia; the ulcerogenic potential of the drug was less than that of indomethacin or naproxen, and less than or similar to that of diclofenac. Although statistical analyses were not consistently available, faecal bleeding and endoscopy studies in humans have indicated overall less GI bleeding and GI mucosal damage with aceclofenac 100mg twice daily than with naproxen 500mg twice daily or diclofenac 50mg 3 times daily. The incidence of endoscopically evident GI mucosal damage was significantly (p < 0.05) lower after aceclofenac 75mg twice daily than after diclofenac 25mg 3 times daily in a 2-week randomised, double-blind study in 30 healthy volunteers.

Overview of Pharmacokinetic Properties

Aceclofenac is rapidly and completely absorbed after oral administration, with peak plasma concentrations (Cmax) being reached 1.25 to 3 hours after ingestion. The volume of distribution (Vd) is approximately 25L, and the drug is highly protein-bound (>99%) in plasma.

Maximum plasma concentrations (Cmax) of aceclofenac and times to Cmax (tmax) are similar after single (100mg) and multiple (100mg twice daily for 7 days) oral doses: in 1 study in 12 young and 12 elderly volunteers, mean Cmax values ranged from 8.94 to 9.86 mg/L and were achieved in 1.08 to 1.37 hours. Areas under plasma drug concentration versus time curves (AUCs) were increased over those seen after single doses in young individuals and decreased in the elderly after multiple doses. No significant differences were observed between young and elderly volunteers in Cmax, absorption half-life or Vd values. The presence of food reduced the rate (increased tmax value) but not the extent (Cmax or AUC) of absorption in trials in young volunteers. The plasma concentration of aceclofenac was approximately twice that in synovial fluid after multiple doses of the drug in patients with knee pain and synovial fluid effusion.

Aceclofenac is metabolised to a major metabolite, 4′-hydroxyaceclofenac, and a number of minor metabolites including 5-hydroxyaceclofenac, diclofenac, 4′-hydroxydiclofenac and 5-hydroxydiclofenac. The drug is eliminated mainly via the renal route, with a plasma elimination half-life (t½β) of approximately 4 hours. In 1 trial, the t½β of aceclofenac was similar after single and multiple doses in elderly volunteers (2.69 and 3.08 hours, respectively), but was increased after multiple doses (from 3.52 to 4.65 hours; p = 0.017) in young participants. Both t½gB values were significantly shorter in elderly than in young volunteers.

Therapeutic Efficacy

Aceclofenac (administered orally unless stated otherwise in all clinical studies discussed in this review) decreases pain, reduces the severity of osteoarthritis and improves the functional capacity of the affected joint in patients with osteoarthritis of the knee. The drug was similar in efficacy to diclofenac, piroxicam and naproxen in randomised, double-blind trials in 49 to 378 patients. Aceclofenac (100mg twice daily for 1 to 6 months) significantly reduced pain levels (expressed on a visual analogue scale), Lequesne Osteoarthritis Severity Index/Severity Index of Gonarthritis and knee function scores, improved the ability to extend and flex the affected knee, and significantly increased numbers of patients with an improvement in signs and symptoms according to investigators’ and patients’ assessments. In 1 trial, paracetamol (acetaminophen) consumption in the first 2 weeks was significantly lower, and patient-perceived pain intensity significantly less, with aceclofenac than with diclofenac. Furthermore, in this trial, the improvement in knee flexion in patients initially unable to straighten the knee was greater after aceclofenac than diclofenac during, but not at the end of, the 3-month study period.

In a nonblind trial, aceclofenac decreased pain, Severity of Gonarthritis Index scores and paracetamol consumption to a similar extent to nabumetone 1 to 2g daily after 12 weeks in 274 patients with osteoarthritis.

The anti-inflammatory and analgesic efficacy of aceclofenac is similar to that of ketoprofen, indomethacin, tenoxicam and diclofenac in patients with rheumatoid arthritis. In randomised, double-blind trials in 169 to 261 patients, aceclofenac (100mg twice daily for 3 or 6 months) significantly reduced relative to baseline joint inflammation, pain intensity and the duration of morning stiffness, and improved hand grip strength. Improvements from baseline in functional capacity were reported in 27% of patients receiving aceclofenac or indomethacin in 1 trial in which this end-point was assessed, and both aceclofenac and ketoprofen improved functional capacity statistically significantly (p < 0.01) in 1 other study.

Aceclofenac reduces pain and morning stiffness and improves mobility of the spine to a similar extent to indomethacin, tenoxicam and naproxen in patients with active ankylosing spondylitis. These effects were observed after aceclofenac 100mg twice daily for 3 months in randomised, double-blind trials involving 104 to 308 patients. In addition, emergency paracetamol use was similar with all agents. In a comparison with naproxen, both agents significantly reduced numbers of patients with moderate or severe pain on movement or at rest (by 55 to 79%; p < 0.05 vs baseline), and increased numbers of patients with no or mild pain and no or slight limitation of movement. The number of patients with moderate or severe limitation of movement decreased from baseline by 92% after treatment with aceclofenac.

In general, the time of onset of action of aceclofenac appears similar to that of comparator agents. In the above trials, significant improvements in symptoms versus baseline were generally apparent by the time of the first assessment at 2 weeks. Withdrawal rates because of lack of efficacy were also similar between aceclofenac and comparator drugs [although the rate was lower with aceclofenac than with ketoprofen in a study in 169 patients with rheumatoid arthritis (4.6 vs 13.4%; p < 0.05)].

The analgesic efficacy of aceclofenac has been shown in comparisons with placebo in patients with moderate to severe dental pain and in comparisons with paracetamol in women undergoing episiotomy. Aceclofenac (150mg intramuscularly for 2 days, then 100mg orally, both twice daily) was superior to diclofenac (75mg twice daily intramuscularly for 2 days, then 50mg 3 times daily orally) in alleviating functional impairment in a 7-day study in 100 patients with acute lumbago; lower back pain decreased progressively from baseline (p < 0.01) with both treatments, and the physician’s overall assessment of efficacy was good or better in more than 85% of aceclofenac and 76% of diclofenac recipients (p < 0.05). Data from noncomparative studies suggest benefit in patients with dysmenorrhoea and in patients with musculoskeletal trauma, although the lack of control groups in these trials limits the scope of any conclusions.

Pharmacoeconomic data derived from 12 of 13 studies (3239 patients) included in a meta-analysis of randomised, double-blind studies have indicated aceclofenac 200 mg/day to be associated with overall daily costs of treatment similar to those of a range of other NSAIDs (direct costs only for a 3-month period from the perspective of a healthcare provider), despite its acquisition cost. This observation was attributed to reductions in costs associated with the management of adverse events and substitution of alternative treatments in patients receiving aceclofenac relative to recipients of diclofenac, indomethacin, naproxen, tenoxicam or ketoprofen.

Tolerability

Most adverse events reported after aceclofenac are mild and reversible and primarily involve the GI system. Most common events include dyspepsia and abdominal pain (≥5% incidence). Dizziness, vertigo, pruritus, rash and dermatitis have been reported with aceclofenac, but the incidence of these events is low (<5%).

Aceclofenac has shown a tolerability profile similar to that with placebo in controlled trials in patients with rheumatoid or osteoarthritis. In individual trials with active comparators, the overall incidence of non-GI adverse events with aceclofenac did not differ significantly from those with ketoprofen, piroxicam, diclofenac or tenoxicam, but was lower than that with naproxen. Withdrawal rates with aceclofenac were generally similar to those with comparator agents. Incidences of adverse events (overall) were significantly lower after aceclofenac than indomethacin in 1 trial, but not in a second. In the first study, major events leading to treatment withdrawal were significantly more frequent in the indomethacin group, and events affecting the CNS were significantly more common after indomethacin than aceclofenac in the second trial. A meta-analysis of 13 randomised, double-blind trials in a total of 3574 patients with rheumatic disease has shown patients receiving aceclofenac to be 1.38 times more likely than those receiving other NSAIDs to be free of adverse events after 3 to 6 months’ treatment (p < 0.001). The rate of withdrawal from treatment because of adverse events was significantly lower with aceclofenac than with other NSAIDs overall in this analysis.

In a large (n = 10 142) nonblind, comparative trial, the overall incidence of adverse events was significantly lower with aceclofenac than with a sustained release formulation of diclofenac (p < 0.001) after 12 months’ treatment; this led to a lower rate of treatment discontinuation with aceclofenac (p < 0.001). Although CNS events were significantly more frequent with aceclofenac than with diclofenac (p = 0.007), the incidence was low in both groups (3 and 1.9%, respectively). Other body systems were affected to a similar extent by the 2 drugs. Incidences of serious adverse events (1.5 and 1.9% for aceclofenac and diclofenac, respectively) did not differ significantly between the 2 treatment groups.

As with other NSAIDs, aceclofenac can elevate circulating levels of hepatic enzymes. Increases after aceclofenac treatment appear to be broadly similar to those observed after diclofenac, indomethacin, naproxen, piroxicam or tenoxicam. However, the effect of aceclofenac on hepatic enzymes is difficult to interpret because many participants in studies in which this effect was examined were receiving concurrent medication, and some had elevated levels at baseline.

Although GI adverse events were reported with similar frequencies after treatment with aceclofenac or comparator agents, withdrawal rates due to these effects were significantly lower after aceclofenac than after ketoprofen or tenoxicam in individual clinical trials. Faecal blood loss was noted in similar numbers of patients receiving aceclofenac or comparator drugs. Nausea, diarrhoea, flatulence, gastritis, constipation, vomiting and ulcerative stomatitis may also occur with aceclofenac (<5% incidence).

The incidence of GI adverse events was significantly lower with aceclofenac than with sustained release diclofenac (p < 0.001) in the nonblind study in 10 142 patients. The meta-analysis of 13 randomised, double-blind studies in 3574 patients indicated that a significantly higher proportion of patients who received aceclofenac than of those who received other NSAIDs (diclofenac, naproxen, piroxicam, indomethacin, tenoxicam or ketoprofen) remained free of GI symptoms after 3 or 6 months’ treatment. Other data from 142 776 Spanish patients have suggested that aceclofenac is associated with a lower incidence of upper GI bleeding events than 10 other NSAIDs (demonstration of statistical significance not included in data analysis).

Increases in blood urea nitrogen and blood creatinine levels have also been reported with aceclofenac treatment (incidence <5%).

Dosage and Administration

The recommended dosage of aceclofenac is 100mg twice daily. Although a dosage reduction is generally not needed in elderly patients or in those with mild renal impairment, monitoring is recommended in such cases. A dosage reduction to 100mg daily is suggested in patients with hepatic impairment. Aceclofenac should be given with caution to elderly patients with renal, hepatic or cardiovascular impairment, and to those receiving other medication.

Aceclofenac should not be administered to patients with peptic ulcers or GI bleeding, moderate or severe renal impairment, sensitivity to aceclofenac or other NSAIDs, or a history of aspirin (acetylsalicyclic acid)- or NSAID-related allergic or anaphylactic reactions. The drug is not recommended in pregnant or breastfeeding women.

Renal and hepatic function and blood counts should be monitored during long term treatment. Persistently elevated hepatic enzyme levels necessitates withdrawal of aceclofenac. Drug interactions associated with the drug are similar to those seen with other NSAIDs.

References

  1. 1.
    Torri G, Vignati C, Agrifoglio E, et al. Aceclofenac versus piroxicam in the management of osteoarthritis of the knee: a double-blind controlled study. Curr Ther Res 1994; 55(5): 576–83CrossRefGoogle Scholar
  2. 2.
    Berkow R, Fletcher AJ, editors. The Merck Manual. 16th ed. Rahway, NJ: Merck Research Laboratories, 1992Google Scholar
  3. 3.
    Díaz C, Rodriguez de la Serna A, Geli C, et al. Efficacy and tolerability of aceclofenac versus diclofenac in the treatment of knee osteoarthritis: a multicentre study. Eur J Rheumatol Inflamm 1996; 16(1): 17–22Google Scholar
  4. 4.
    Creamer P, Hochberg MC. Osteoarthritis. Lancet 1997 Aug 16; 350: 503–9PubMedCrossRefGoogle Scholar
  5. 5.
    Gonzalez E, de la Cruz C, de Nicola’ s R, et al. Long-term effect of nonsteroidal anti-inflammatory drugs on the production of cytokines and other inflammatory mediators by blood cells of patients with osteoarthritis. Agents Actions 1994; 41: 171–8PubMedCrossRefGoogle Scholar
  6. 6.
    Martel-Pelletier J, Cloutier J-M, Pelletier J-P. Effects of aceclofenac and diclofenac on synovial inflammatory factors in human osteoarthritis. Clin Drug Invest 1997 Sep; 14: 226–32CrossRefGoogle Scholar
  7. 7.
    Dingle JT. The effect of NSAIDs on human articular cartilage glycosaminoglycan synthesis. Eur J Rheumatol Inflamm 1996; 16(1): 47–52Google Scholar
  8. 8.
    Dingle JT, Parker M. NSAID stimulation of human cartilage matrix synthesis: a study of the mechanism of action of aceclofenac. Clin Drug Invest 1997 Nov; 14: 353–62CrossRefGoogle Scholar
  9. 9.
    Pasero G, Marcolongo R, Serni U, et al. A multi-centre, double-blind comparative study of the efficacy and safety of aceclofenac and diclofenac in the treatment of rheumatoid arthritis. Curr Med Res Opin 1995; 13(6): 305–15PubMedCrossRefGoogle Scholar
  10. 10.
    Arnett FC, Edworthy SM, Bloch DA, et al. The Americ an Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988 Mar; 31(3): 315–24PubMedCrossRefGoogle Scholar
  11. 11.
    Pasero G, Ruju G, Marcolongo R, et al. Aceclofenac versus naproxen in the treatment of ankylosing spondylitis: a double-blind, controlled study. Curr Ther Res 1994; 55(7): 833–42CrossRefGoogle Scholar
  12. 12.
    Brogden RN, Wiseman LR. Aceclofenac: a review of its pharmacodynamic properties and therapeutic potential in the treatment of rheumatic disorders and in pain management. Drugs 1996 Jul; 52: 113–24PubMedCrossRefGoogle Scholar
  13. 13.
    Cecchettin M, Cerea P, Torri G. Therapeutic efficacy of aceclofenac and diclofenac in acute knee arthroses: a study of E2-prostaglandin levels in synovial fluid and in serum. Clin Trials J 1988; 25(2): 144–51Google Scholar
  14. 14.
    Henrotin Y, de Laval X, Mathy-Hartet M, et al. In vitro effects of aceclofenac and its metabolites on the production by chondrocytes of inflammatory mediators. Inflamm Res. In pressGoogle Scholar
  15. 15.
    Yamazaki R, Kawai S, Matsuzaki T, et al. Aceclofenac blocks prostaglandin E2 production following its intracellular conversion into cyclooxygenase inhibitors. Eur J Pharmacol 1997 Jun 25; 329: 181–7PubMedGoogle Scholar
  16. 16.
    Yamazaki R, Kawai S, Matsumoto T, et al. Hydrolytic activity is essential for aceclofenac to inhibit cyclooxygenase in rheumatoid synovial cells. J Pharmacol Exp Ther 1999; 289: 676–81PubMedGoogle Scholar
  17. 17.
    Garcia-Vicuña R, González-Alvaro I, Carmona L, et al. Aceclofenac, a new NSAID, diminishes the neutrophil expression of cell adhesion molecules involved in interaction with endothelium. Arthritis Rheum 1995; 38: S156Google Scholar
  18. 18.
    Akimoto H, Yamazaki R, Hashimoto S, et al. 4′-Hydroxy aceclofenac suppresses the interleukin-1-induced production of promatrix metalloproteinases and release of sulfated-glycosaminoglycans from rabbit articular chondrocytes. Eur J Pharmacol 2000; 401: 429–36PubMedCrossRefGoogle Scholar
  19. 19.
    Yamazaki R, Kawai S, Mizushima Y, et al. A major metabolite of aceclofenac, 4′-hydroxy aceclofenac, suppresses the production of interstitial pro-collagenase/proMMP-1 and prostromelysin-1/proMMP-3 by human rheumatoid synovial cells. Inflamm Res 2000; 49: 133–8PubMedCrossRefGoogle Scholar
  20. 20.
    Grau M, Guasch J, Montero J, et al. Pharmacology of the potent new non-steroidal anti-inflammatory agent aceclofenac. Arzneimittelforschung 1991; 41: 1265–76PubMedGoogle Scholar
  21. 21.
    Arañó A, Zapatero MI, Basi N, et al. Comparison of the anti-inflammatory effect and gastrointestinal tolerability of aceclofenac and diclofenac. Arzneimittelforschung 1996 Apr; 46: 398–400PubMedGoogle Scholar
  22. 22.
    Yanagawa A, Kudo T, Shimada J, et al. Endoscopic study of the damaging action of diclofenac Na, aceclofenac and its placebo on the gastric and duodenal mucosa [abstract]. Rheumatology in Europe 1995; 24 Suppl. 3: 220Google Scholar
  23. 23.
    Wassif W, Bjarnason I. A comparison of the effects of aceclofenac and diclofenac on gastrointestinal blood loss. Br J Clin Res 1992; 3: 109–14Google Scholar
  24. 24.
    Mundo F, Mitrani C, Sánchez H, et al. Endoscopie assessment of gastric mucosa injury with the use of non-steroidal anti-inflammatory drugs: aceclofenac vs naproxen, single-blind, controlled, prospective study [abstract]. Am J Gastroenterol 1996 Sep; 91: 1922Google Scholar
  25. 25.
    Lidbury P, Vojnovic I, Warner T. COX-2/COX-1 selectivity of aceclofenac in comparison with celecoxib and rofecoxib in the human whole blood assay [abstract]. Osteoarthritis Cartilage 2000; 8 Suppl. B: S40–1Google Scholar
  26. 26.
    de Levai X, Dogne JM, Delarge J, et al. Evaluation of classical NSAIDs and COX-2 selective inhibitors on purified ovine enzymes and human whole blood [abstract no. AB0223]. Proceedings of the European League Against Rheumatism (EULAR); 2001 Jun 13–16; PragueGoogle Scholar
  27. 27.
    Blanco FJ, Maneiro E, de Toro FJ, et al. Effect of NSAIDs on synthesis of IL-1 receptor antagonist (IL-1 Ra) by human articular chondrocytes [abstract]. Osteoarthritis Cartilage 2000; 8 Suppl. B: S27Google Scholar
  28. 28.
    Yanagawa A, Endo T, Kusakari K, et al. Endoscopie evaluation of aceclofenac-induced gastroduodenal mucosal damage: a double-blind comparison with sodium diclofenac and placebo. Jpn J Rheumatol 1998; 8(3): 249–59CrossRefGoogle Scholar
  29. 29.
    Bort R, Ponsoda X, Carrasco E, et al. Metabolism of aceclofenac in humans. Drug Metab Dispos 1996 Aug; 24: 834–41PubMedGoogle Scholar
  30. 30.
    Creamer J. A comparison of the pharmacokinetics of single and repeated doses of aceclofenac in young and elderly volunteers. Br J Clin Res 1992; 3: 99–107Google Scholar
  31. 31.
    Crema A, Crema F, Parnham MJ, et al. Effect of food on the bioavailability of aceclofenac tablets in healthy volunteers. EurJ Clin Res 1995; 7: 155–60Google Scholar
  32. 32.
    Wood SG, Fitzpatrick K, Brodie RR, et al. Pharmacokinetics and metabolism of a new NSAID/analgesic aceclofenac in man [abstract]. Pharm Res 1990; 7(9): S–212Google Scholar
  33. 33.
    Honorato J, Caballero R, Giorgiani G, et al. Dose-analgesic response study and aceclofenac plasma levels in humans. Curr Ther Res 1990; 47(4): 605–11Google Scholar
  34. 34.
    Preservex tablets. In: Walker G, editor. ABPI compendium of data sheets and summaries of product characteristics 1999–2000. London: Datapharm Publications Ltd, 1999: 1680–1Google Scholar
  35. 35.
    Pérez Busquier M, Calero E, Rodriguez M, et al. Comparison of aceclofenac with piroxicam in the treatment of osteoarthritis. Clin Rheumatol 1997 Mar; 16: 154–9PubMedCrossRefGoogle Scholar
  36. 36.
    Ward DE, Veys EM, Bowdler JM, et al. Comparison of aceclofenac with diclofenac in the treatment of osteoarthritis. Clin Rheumatol 1995 Nov; 14: 656–62PubMedCrossRefGoogle Scholar
  37. 37.
    Kornasoff D, Frerick H, Bowdler J, et al. Aceclofenac is a well-tolerated alternative to naproxen in the treatment of osteoarthritis. Clin Rheumatol 1997 Jan; 16: 32–8PubMedCrossRefGoogle Scholar
  38. 38.
    Gijón Baños JG. Efficacy and safety of nabumetone in the treatment of knee osteoarthritis: a comparative clinical trial versus aceclofenac. Knee Arthrosis Nabumetone Study Group [in Spanish]. Med Clin (Barc) 1997; 109(4): 130–4Google Scholar
  39. 39.
    Giorgianni G, Ottaviani C, Soliano A. Efficacy and tolerability of aceclofenac versus ketoprofen in the treatment of rheumatoid arthritis. Curr Ther Res Clin Exp 1992; 51: 175–84Google Scholar
  40. 40.
    Ritchie DM, Boyle JA, McInnes JM, et al. Clinical studies with an articular index for the assessment of joint tenderness in patients with rheumatoid arthritis. Q J Med 1968; 37(147): 393–406PubMedGoogle Scholar
  41. 41.
    Kornasoff D, Maisenbacher J, Bowdler J, et al. The efficacy and tolerability of aceclofenac compared to indomethacin in patients with rheumatoid arthritis. Rheumatol Int 1996 Mar; 15: 225–30PubMedCrossRefGoogle Scholar
  42. 42.
    Martín-Mola E, Gijón-Baños J, Ansoleaga JJ. Aceclofenac in comparison to ketoprofen in the treatment of rheumatoid arthritis. Rheumatol Int 1995; 15: 111–6PubMedCrossRefGoogle Scholar
  43. 43.
    Perez-Ruiz F, Alonso-Ruiz A, Ansoleaga JJ. Comparative study of the efficacy and safety of aceclofenac and tenoxicam in rheumatoid arthritis. Clin Rheumatol 1996 Sep; 15: 473–7PubMedCrossRefGoogle Scholar
  44. 44.
    Steinbrocker O, Traeger C, Battermann RC. Therapeutic criteria in rheumatoid arthritis. JAMA 1949; 140: 659–62CrossRefGoogle Scholar
  45. 45.
    Villa Alcázar LF, de Buergo MA, Lenza HR, et al. Aceclofenac is as safe and effective as tenoxicam in the treatment of ankylosing spondylitis: a 3 month multicenter comparative trial. J Rheumatol 1996 Jul;23: 1194–9PubMedGoogle Scholar
  46. 46.
    Batlle-Gualda E, Figueroa M, Ivorra J, et al. The efficacy and tolerability of aceclofenac in the treatment of patients with ankylosing spondylitis: a multicenter controlled clinical trial. J Rheumatol 1996 Jul;23: 1200–6PubMedGoogle Scholar
  47. 47.
    Sainz-Olalla F. Analgesic efficacy of aceclofenac: double-blind controlled study vs placebo in odontalgia. CurrTher Res Clin Exp 1988; 43(5): 900–2Google Scholar
  48. 48.
    Bubani G. The analgesic activity and tolerability of aceclofenac in the treatment of odontalgia: a double-blind placebocontrolled evaluation. Clin Trials J 1988; 25(4): 244–53Google Scholar
  49. 49.
    Puigvert Torrent A. Dose-response study of the analgesic activity of aceclofenac in odontalgia following extraction of the third molar. Drug Invest 1990; 2(2): 132–6CrossRefGoogle Scholar
  50. 50.
    Yscla A. Aceclofenac and paracetamol in episiotomal pain. Drugs Exp Clin Res 1988; 14(7): 491–4PubMedGoogle Scholar
  51. 51.
    Movilia PG. Evaluation of the analgesic activity and tolerability of aceclofenac in the treatment of post-episiotomy pain. Drugs Exp Clin Res 1989; 15(1): 47–51PubMedGoogle Scholar
  52. 52.
    da Fonseca AM, Bagnoli VR. A multicenter study of the efficacy and tolerability of aceclofenac in the treatment of primary dysmenorrhea [in Portuguese]. Rev Bras Med 1999; 56(3): 169–73Google Scholar
  53. 53.
    Agrifoglio E, Benvenuti M, Gatto P, et al. Aceclofenac: a new NSAID in the treatment of acute lumbago. Multicentre single blind study vs diclofenac. Acta Ther 1994; 20(1–2): 33–45Google Scholar
  54. 54.
    de Barros Filho TEP, Ortiz J, Gomes Vialle LR, et al. Study of the efficacy and tolerability of aceclofenac in the management of low-back pain [in Portuguese]. Rev Bras Med 1999; 56(1/2): 60–4Google Scholar
  55. 55.
    Köberle G, Couto Magalhaes AA, Jansen Paccola CA, et al. Multicenter, open study of the use of aceclofenac 100 mg, twice a day, in the treatment of muscular-skeletal traumas [in Portuguese]. Rev Bras Med 1998; 55(1/2): 63–9Google Scholar
  56. 56.
    Ishida A, Adames MK. Study of the efficacy and tolerability of aceclofenac in the treatment of post-traumatic acute process in orthopaedics and traumatology [in Portuguese]. Rev Bras Med 1997; 54(8): 687–93Google Scholar
  57. 57.
    Peris F, Martínez E, Badia X, et al. Iatrogenic cost factors incorporating mild and moderate adverse events in the economic comparison of aceclofenac and other NSAIDs. Pharmacoeconomics 2001; 19(7): 779–90PubMedCrossRefGoogle Scholar
  58. 58.
    Peris F, Bird HA, Serni U, et al. Treatment compliance and safety of aceclofenac versus standard NSAIDs in patients with common arthritic disorders: a meta-analysis. Eur J Rheumatol Inflamm 1996; 16(1): 37–45Google Scholar
  59. 59.
    Huskisson EC, Irani M, Murray F. A large prospective open-label, multicentre SAMM study, comparing the safety of aceclofenac with diclofenac in patients with rheumatic disease. Eur J Rheumatol Inflamm 2000; 17(1): 1–7Google Scholar
  60. 60.
    Epelde F, Boada L. Leukocytoclastic vasculitis and hemoptysis after treatment with aceclofenac [letter]. Ann Pharmacother 1995 Nov;29: 1168PubMedGoogle Scholar
  61. 61.
    Nú~nez M, Miralles ES, Harto A, et al. Hypersensitivity vasculitis associated with aceclofenac [letter]. J Dermatol Treat 1995; 6(1): 54Google Scholar
  62. 62.
    Morros R, Figueras A, Capellà D, et al. Hypersensitivity vasculitis related to aceclofenac [letter]. Br JRheumatol 1997 Apr; 36: 503–4CrossRefGoogle Scholar
  63. 63.
    Prescott LF. Effects of non-narcotic analgesics on the liver. Drugs 1986; 32 Suppl. 4: 129–47PubMedCrossRefGoogle Scholar
  64. 64.
    Llorente MJ. Specific types of nonsteroidal anti-inflammatory drugs and relative risk of upper gastrointestinal bleeding [abstract]. Br J Rheumatol 1998; 37 Suppl. 1:115Google Scholar
  65. 65.
    Speight TM, Holford N, editors. Avery’ s drug treatment. 4th ed. Auckland, New Zealand: Adis International Limited, 1997Google Scholar
  66. 66.
    Lane NE, Thompson JM. Management of osteoarthritis in the primary-care setting: an evidence-based approach to treatment. Am J Med 1997 Dec 29; 103 Suppl. 6A: 25S–30SPubMedCrossRefGoogle Scholar
  67. 67.
    Cashman JN. The mechanisms of action of NS AIDs in analgesia. Drugs 1996; 52 Suppl. 5: 13–23PubMedCrossRefGoogle Scholar
  68. 68.
    Stolz J. Aceclofenac may offer advantages in arthritis management. Inpharma 1998 May 9; 1136: 3–4CrossRefGoogle Scholar
  69. 69.
    Peterson WL, Cryer B. COX-1-sparing NSAIDs — is the enthusiasm justified? JAMA 1999; 282(20): 1961–3PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 2001

Authors and Affiliations

  • Mukta Dooley
    • 1
  • Caroline M. Spencer
    • 1
  • Christopher J. Dunn
    • 1
  1. 1.Adis International LimitedMairangi Bay, Auckland 10New Zealand

Personalised recommendations