Abstract
Synopsis
Aceclofenac is a phenylacetic acid derivative with anti-inflammatory and analgesic properties similar to those of diclofenac. However, preclinical studies suggest that the potential of aceclofenac to cause gastrointestinal damage is less than that of diclofenac.
Double-blind comparative trials indicate that the efficacy of aceclofenac is at least equivalent to that of ketoprofen and similar to that of indomethacin and diclofenac in patients with rheumatoid arthritis, similar to that of diclofenac and piroxicam in patients with osteoarthritis of the knee and similar to that of ten-oxicam, indomethacin and naproxen in patients with ankylosing spondylitis. The analgesic efficacy of aceclofenac 100mg is more prolonged than that of paracetamol (acetaminophen) 650mg.
If the apparently improved gastrointestinal tolerability of aceclofenac compared with diclofenac is confirmed by wider clinical experience, aceclofenac will have the potential to become a preferred initial drug in an individualised NSAID regimen in patients with rheumatic disorders.
Pharmacodynamic Properties
The anti-inflammatory activity of aceclofenac has been shown to be similar to that of diclofenac in animal models of acute and chronic inflammation. In patients with osteoarthritis of the knee, basal and stimulated prostaglandin E2 (PGE2) production by blood mononuclear and polymorphonuclear cells was inhibited to a similar extent by aceclofenac 200 mg/day and diclofenac 150 mg/day for 6 months. Aceclofenac 225 mg/day for 6 days significantly decreased synovial fluid PGE2 levels in patients with knee pain and synovial effusion.
The analgesic activity of aceclofenac was similar to that of diclofenac in rodent models and the antipyretic potency of aceclofenac was about half that of diclofenac in rats with brewer’s yeast-induced hyperthermia. In vitro, aceclofenac stimulated glycosaminoglycan synthesis in osteoarthritic cartilage, indicating potential to maintain matrix synthesis and repair.
The ulcerogenic activity of a single dose of aceclofenac in rats assessed from indices of lesion severity was about 4- and 7-fold less than that of diclofenac and indomethacin, respectively. After multiple doses, the ulcerogenic effect of aceclofenac was about 1.5- to 2-fold less than that of diclofenac. During administration of aceclofenac 200 mg/day for 10 days to healthy volunteers, mean daily blood loss relative to baseline in faecal samples (following p51Cr labelling of red blood cells) was lower than that induced by diclofenac 150 mg/day.
Pharmacokinetic Properties
After oral administration of a single 100mg dose, mean maximum plasma aceclofenac concentrations (Cmax) of 6.8 to 8.9 mg/L were reached in about 1.4 to 2 hours. Cmax and the area under the plasma concentration-time curve (AUC) increased linearly after administration of single doses of aceclofenac 50, 100 and 150mg, and the pharmacokinetic properties of the drug were generally unchanged during multiple-dose administration in both young and elderly volunteers. The presence of food did not alter the pharmacokinetic parameters of aceclofenac.
The mean concentration of aceclofenac in synovial fluid is about half that in plasma. The main metabolite of aceclofenac is 4-hydroxy-aceclofenac; minor metabolites include diclofenac and 4-hydroxy-diclofenac. The low plasma concentrations and AUC values for the metabolites indicate that aceclofenac is principally responsible for the pharmacological activity. Approximately 70% of the drug is eliminated in the urine and 20% in the faeces. Mean elimination half-life values between 3.5 and 6.2 hours have been reported.
Therapeutic Efficacy
Double-blind trials have compared the efficacy of aceclofenac 100mg twice daily with that of ketoprofen 50mg 3 times daily, diclofenac 50mg 3 times daily or indomethacin 50mg twice daily in the treatment of patients with rheumatoid arthritis. All drugs significantly reduced the Ritchie index, pain and the duration of morning stiffness, and increased grip strength compared with baseline values. The drugs were generally of similar efficacy, although the onset of effect of aceclofenac appeared to be faster than that of ketoprofen. Aceclofenac 100mg twice daily showed similar efficacy to that of diclofenac 50mg 3 times daily and piroxicam 20mg once daily in improving symptoms in patients with osteoarthritis of the knee. Although the overall efficacy did not differ significantly between treatment groups according to investigators, patient-assessed pain improved in a greater percentage of aceclofenac than diclofenac recipients in one study.
Aceclofenac 100mg twice daily, tenoxicam 20mg once daily, indomethacin 100mg daily (25mg morning and noon and 50mg in the evening) and naproxen 500mg twice daily were similarly effective in alleviating pain and morning stiffness and improving spinal mobility in patients with ankylosing spondylitis.
The analgesic efficacy of single doses of aceclofenac 50, 100 and 150mg was greater than that of placebo in patients with moderate to severe tooth pain or pain caused by episiotomy or extraction of impacted third molars. Aceclofenac 100 or 150mg was longer acting than aceclofenac 50mg, and in patients with postepisiotomy pain aceclofenac 100mg was more effective than paracetamol (acetaminophen) 650mg. The duration of analgesic effect of intramuscular aceclofenac 150mg twice daily was greater than that of diclofenac 75mg twice daily in patients with acute lumbago. Pain and swelling associated with soft tissue injuries were alleviated to a similar extent by a topical formulation of a cream containing either aceclofenac 1.5% or piroxicam 1%.
Tolerability
Data regarding the incidence of adverse events associated with aceclofenac are available only from clinical trial reports. Gastrointestinal events including indigestion, diarrhoea, nausea, abdominal pain and flatulence have been reported in 2 to 24.5% of patients treated with aceclofenac. The incidence of gastrointestinal adverse effects has generally been lower with aceclofenac than the comparators; however, endoscopy was not performed in clinical trials. Although differences did not generally reach the level of statistical significance in individual studies, a meta-analysis indicated that the incidence of adverse events and overall withdrawal rate were lower and the gastrointestinal tolerability of aceclofenac better than that of other NSAIDs. The incidence of adverse events was similar between aceclofenac and placebo in placebo-controlled trials. Although available data indicate that aceclofenac has a minimal effect on liver function at therapeutic dosages, the drug modestly increased mean levels of the hepatic enzymes aspartate and alanine aminotransferase. Its effect on liver function relative to that of other NSAIDs remains to be determined.
Dosage and Administration
The usual oral dosage of aceclofenac is 100mg twice daily for the treatment of arthritic disorders and moderate to severe pain in adults. Aceclofenac, like other NSAIDs, should be administered with caution to patients with a history of peptic ulcer or dyspepsia.
Similar content being viewed by others
References
Grau M, Guasch J, Montero JL, et al. Pharmacology of the potent new non-steroidal anti-inflammatory agent aceclofenac. Arzneimittel Forschung 1991 Dec; 41: 1265–76
Grau M, Montero JL, Guasch J, et al. The pharmacological profile of aceclofenac, a new nonsteroidal antiinflammatory and analgesic drug. Agents Actions 1991; 32 Suppl.: 125–9
Yamazaki R, Matsuzaki T, Kaneda N, et al. Anti-inflammatory effect of aceclofenac on inflammatory cells [abstract]. Rheumatol Eur 1995; 24 Suppl.3: 273
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 [abstract]. Arthritis Rheum 1995 Sep; 38 Suppl.: 156
Gonzalez E, de la Cruz C, de Nicolas 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 May; 41: 171–8
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): 144–51
Dingle JT. The effect of NSAID on human articular cartilage glycosaminoglycan synthesis. Eur J Rheumatol Inflamm 1996; 16: 47–52
Gropper S, Duque A, Arano A, et al. A comparison of anti-inflammatory activity and gastrointestinal damage of two drugs: aceclofenac and diclofenac [abstract]. Methods Find Exp Clin Pharmacol 1994; 16 Suppl.1: 78
Rimbau V, Fernandez MF, Guirao I, et al. Comparative study of the gastrointestinal tolerance of diclofenac and aceclofenac. Farmaco Ed Prat 1988 Jan; 43: 19–26
Wassif W, Bjarnason I. A comparison of the effects of aceclofenac and diclofenac on gastrointestinal blood loss. Br J Clin Res 1992; 3: 109–14
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]. Rheumatol Eur 1995; 24 Suppl.3: 220
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: 99–107
Crema A, Crema F, Parnham MJ, et al. Effect of food on the bioavailability of aceclofenac tablets in healthy volunteers. Eur J Clin Res 1995; 7: 155–60
Brodie RR, Chasseaud LF, Irons SR, et al. Pharmacokinetics and bioavailability of the anti-inflammatory agent aceclofenac after single oral doses to human subjects — a dose proportionality study. Clin Drag Invest. In press
Honorato J, Caballero R, Giorgiani G, et al. Dose-analgesic response study and aceclofenac plasma levels in humans. Curr Ther Res Clin Exp 1990 Apr; 47: 605–11
Wood SG, Fitzpatrick K, Brodie R, et al. Pharmacokinetics and metabolism of a new NSAID/analgesic aceclofenac in man [abstract]. Pharm Res 1990 Sep; 7 Suppl.: 212
Ballesteros R, Ansoleaga JJ, Tapounet R. The efficacy and tolerance of aceclofenac in rheumatoid arthritis. A double-blind study vs placebo. Clin Trials J 1990; 27(1): 12–9
Dawson AJ, Roma J, Bowdler JM. Aceclofenac in the treatment of rheumatoid arthritis: a multicentre, double-blind, randomised, placebo-controlled study. Eur J Rheumatol Inflamm 1996; 16: 23–8
Hunter JA, Parnham MJ, Grasi Balaguer X. Aceclofenac in rheumatiod arthritis: a useful and novel anti-inflammatory. Clin Rheumatol. In press
Arnett FC, Edworthy SM, Bloch SM, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988; 31: 315–24
Obach J, Asensi E, Benito P, et al. Effectiveness and tolerance of aceclofenac versus ketoprofen in the treatment of rheumatoid arthritis [in Spanish]. Rev Esp Reumatol 1992; 19(6): 263–8
Martín-Mola E, Gijón-Baños J, Ansoleaga JJ. Aceclofenac in comparison to ketoprofen in the treatment of rheumatoid arthritis. Rheumatol Int 1995 Sep; 15: 111–6
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 1996; 13: 305–15
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; 15: 225–30
Ritchie DM, Boyle JA, McInes JM, et al. Clinical studies with an articular index for assessment of joint tenderness in patients with rheumatoid arthritis. Q J Med 1969; 37: 393–410
Steinbrocker O, Traeger C, Battermann RC. Therapeutic criteria in rheumatoid arthritis. JAMA 1949; 140: 659–62
Fehr K, Miehle W, Schattenkirchner M, et al. Rheumatologie in Praxis und Klinik. 1989
Giorgianni G, Ottaviani Soliano A. Efficacy and tolerability of aceclofenac versus ketoprofen in the treatment of rheumatoid arthritis. Curr Ther Res Clin Exp 1992 Feb; 51: 175–84
Belmonte MA, Olmedo J, Benito P, et al. Efficacy and tolerance of aceclofenac in the treatment of gonarthrosis [in Spanish]. Rev Esp Reumatol 1992; 19(4): 142–6
Diaz C, Rodriguez A, Geli C et al. Comparison of aceclofenac and diclofenac in osteoarthritic pain. Curr Ther Res Clin Exp 1988; 44(2): 252–6
Ward DE, Veys EM, Bowdler JM. Comparison of aceclofenac with diclofenac in the treatment of osteoarthritis. Clin Rheumatol 1995 Nov; 14: 656–62
Diaz C, Rodríguez de la Serna A, Geli C et al. Efficacy and tolerability of aceclofenac vs diclofenac in the treatment of knee osteoarthritis. A multicenter study. Eur J Rheumatol Inflamm 1996; 16: 17–22
Torri G, Vignati Agrifoglio E, et al. Aceclofenac versus piroxicam in the management of osteoarthritis of the knee: a double-blind controlled study. Curr Ther Res Clin Exp 1994; 55(5): 576–83
Torrejón VA. Treatment of severe rheumatic pain with aceclofenac. Results of a comparative study vs. placebo. Acta Ther 1988; 14(3): 275–80
Birell DH, Roma J, Bowdler JM. Evaluation of the efficacy and safety of aceclofenac in the treatment of osteoarthritis. Br J Clin Res 1995; 6: 45–55
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 Clin Exp 1994; 55(7): 833–42
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. In press
Villa L, Alvarez de Buergo M, Rico H, et al. Aceclofenac is as safe and effective as tenoxicam in the treatment of ankylosing spondylitis: a three month, multicentre, conparative trial. J Rheumatol. In press
Sainz Olalla-F. Analgesic efficacy of aceclofenac: double-blind controlled study vs placebo in odontalgia. Curr Ther Res Clin Exp 1988; 43(5): 900–2
Bubani G. The analgesic activity and tolerability of aceclofenac in the treatment of odontalgia. A double-blind placebo-controlled evaluation. Clin Trials J 1988; 25(4): 244–53
Movilia PG. Evaluation of the analgesic activity and tolerability of aceclofenac in the treatment of post-episiotomy pain. Drugs Exp Clin Res 1989; 15: 47–51
Yscla A. Aceclofenac and paracetamol in episiotomal pain. Drugs Exp Clin Res 1988; 14: 491–4
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): 132–6
Agrifoglio E, Benvenuti M, Gatto P, et al. Aceclofenac: a new NS AID in the treatment of acute lumbago. Multicentre single blind study vs diclofenac. Acta Ther 1994; 20(1–2): 33–45
Torri G. Efficacy and tolerability of aceclofenac in the treatment of gonalgia: controlled double-blind study vs diclofenac. Curr Ther Res Clin Exp 1987; 42(3): 453–7
Tessari L, Ceciliani L, Belluati A, et al. Aceclofenac cream versus piroxicam cream in the treatment of patients with minor traumas and phlogistic affections of soft tissues: a double-blind study. Curr Ther Res Clin Exp 1995 Jul; 56: 702–12
Nunez M, Miralies ES, Harto A. Hypersensitivity vasculitis associated with aceclofenac. J Dermatol Treat 1995 Mar; 6: 54
Epelde F, Boada L. Leukocytoclastic vasculitis and hemoptysis after treatment with aceclofenac. Ann Pharmacother 1995 Nov; 29: 1168
Peris F, Bird HA, Serni U, et al. Treatment compliance and safely of aceclofenac versus standard NSAIDs in patients with common arthritic disorders: a meta-analysis. Eur J Rheumatol Inflamm 1996; 16: 37–45
Prescott L. Effects of non-narctoic analgesics on the liver. Drugs 1986; 32 Suppl.4: 129–47
Zaragoza-Marcet A, Alfonso-Moreno V, Roig-Catala E. NS AID-induced hepatotoxicity: aceclofenac and diclofenac [in Spanish]. Rev Esp Enferm Dig 1995 Jun; 87: 472–5
Marsicano LJ, Ocampo ME. Hepatic tolerance of aceclofenac [in Spanish]. Gen Gen 1994; 48(4): 250–5
Author information
Authors and Affiliations
Additional information
Various sections of the manuscript reviewed by: E. Batlle-Gualda, Sección de Rheumatología, Hospital General Universitario de Alicante, Alicante, Spain; H. A. Bird, Clinical Pharmacology Unit, Research School of Medicine, University of Leeds, Leeds, England; I. Bjarnason, Department of Clinical Biochemistry, King’s College School of Medicine and Dentistry, London, England; A. Crema, Section of Pharmacology and Toxicology, Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy; M. S. Irani, Ashford Hospital, Ashford, Middlesex, England; F. McKenna, Rheumatic Diseases Unit, Trafford General Hospital, Manchester, England; M. M. Wolfe, Brigham and Women’s Hospital, Gastroenterology Division, Boston, Massachusetts, USA; A. Yanagawa, Institute of Medical Science, St Marianna University, Kawasaki, Kanagawa, Japan.
Rights and permissions
About this article
Cite this article
Brogden, R.N., Wiseman, L.R. Aceclofenac. Drugs 52, 113–124 (1996). https://doi.org/10.2165/00003495-199652010-00008
Published:
Issue Date:
DOI: https://doi.org/10.2165/00003495-199652010-00008