Bristaflam is a global pharmaceutical brand of the NSAID aceclofenac. It has been used in clinical practice for over 15 years and is registered in more than 60 countries. Clinical trials have shown Bristaflam to be as effective as other NSAIDs like diclofenac, naproxen, and indomethacin in treating conditions like osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis. While some NSAIDs are associated with a higher risk of gastrointestinal bleeding, studies found Bristaflam to have a low risk, similar to other NSAIDs. Overall, Bristaflam is considered to be an effective analgesic with a favorable safety profile.

1. 1
Bristafalm – EFFECTIVELY SAFE
(OR SAFELY EFFECTIVE)?

2. A GLOBAL BRAND
Bristaflam

3. Bristaflam key dates
1982 Bristaflam is synthesized
1986 First human Clinical Trial
1992 First launch in Spain
1997 Approval by mutual recognition in Europe
2004 Last launch in France

4. 1992-1994
Bristaflam a global presence
1992
Spain
1993
Portugal
Dominican Republic
Costa Rica
Honduras
Panama
El Salvador
Nicaragua
Venezuela
Bolivia
Paraguay
1994
Mexico
Peru
Argentina
Date of launch

5. 1995
Korea
Guatemala
Colombia
Chile
Senegal
Mali
Burkina Faso
Niger
Togo
Benin
Ivory Coast
Gabon
Cameroon
Congo
1996
UK
Greece
Cyprus
Ghana
Kenya
Madagascar
Mauritius
Brazil
1997
Ireland
Sweden
Denmark
Germany
Bristaflam a global presence
1995-
1997
Date of launch

6. 1998
Luxembourg
Belgium
Morocco
Egypt
Lebanon
1999
Finland
Switzerland
Austria
2000
The Netherlands
1998-2000
Date of launch
Bristaflam a global presence

7. 2001
Hungary
2002
Italy
Russia
2003-2004
France
Portugal (Relaunch)
Greece (Relaunch)
Eastern countries
2005
Latvia
2006
Slovakia
Romania
2001-2005
Bristaflam a global presence
Date of launch

8. Registered
in more than 60 countries
Bristaflam a global presence

9. UK
France
Aceclofenac present in all key European markets
Germany
Belgium
Italy
Spain
Portugal

10. Aceclofenac in Egypt is available as
100 mg/twice daily
TABLETS

11. PRODUCT OVERVIEW

12. Extensive experience that offers:
Bristaflam has been used in clinical practice for
Bristaflam is registered in more than
Bristaflam has over
have been treated with Bristaflam.
more than 15 years.
60 countries worldwide.
1.5 billion Defined Daily Doses Administered.
100 million patientsOver
… the guarantee of reliability.

13. Pharmacodynamics: Multifactorial mechanism of action
PHARMACODYNAMIC PROFILE
GASTRIC TISSUE
COX-1
PGE
GASTRIC
PROTECTION
INJURY
INFLAMMATION SITE
Adhesion molecules
Neutrophil migration
COX-2
PGE2
Pro-inflammatory cytokines Free radicals
INFLAMMATION

14. Pharmacodynamics: Multifactorial mechanism of action
PHARMACODYNAMIC PROFILE
GASTRIC TISSUE
COX-1
PGE
GASTRIC
PROTECTION
Weak inhibition
of COX 1
TOLERABILITY EFFICACY
INFLAMMATION SITE
INJURY
PGE2
Free radicals
INFLAMMATION
COX-2
Neutrophil migration
Adhesion molecules
Pro-inflammatory cytokinesReduces the expression
of adhesion molecules
Reduces migration
and adhesion
of neutrophils
Inhibits
production
of PGE2
Presents
antioxidant
properties

15. inhibits the expression of COX-2
Multifactorial impact on inflammation
Inhibits production of IL-1β
Inhibits production of TNF-α
Inhibits prostaglandin synthesis (intense inhibition of PGE2)
Induces IL-1Ra synthesis (receptor antagonist of IL-1β)
BRISTAFLAM PHARMACODYNAMIC PROFILE
Reduces cell adhesion molecule expression
Presents anti-oxidant properties: action on free radicals

16. CHRONIC
DISORDERS

17. OSTEOARTHRITIS (OA)
The most common arthropathy
ANKYLOSING SPONDYLITIS (AS)
Less common than RA
RHEUMATOID ARTHRITIS (RA)
Affects young and elderly patients
CHRONIC DISEASES

18. Diclofenac
Piroxicam
Naproxen
EFFICACY DATA
Proven efficacy in Osteoarthritis
In Osteoarthritis, similar efficacy to

19. Proven efficacy in Osteoarthritis: key publications
EFFICACY DATA
Diaz C, Rodriguez 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.
Ward D, Veys E, Bowdler J. Comparison of Aceclofenac with Diclofenac
in the treatment of Osteoarthritis. Clin Rheumatol 1995; 14: 656-62.
Torri G, Vignati C, Agrifoglio E, et al. Aceclofenac vs. Piroxicam in the
management of Osteoarthritis of the knee: a double-blind controlled study.
Curr Ther Res Clin Exp 1994; 55: 576–83.
Perez-Busquier M, Carero E, Rodriguez M, et al. Comparison of Aceclofenac
with Piroxicam in the treatment of Osteoarthritis. Clin Rheumatol 1997;
16 (2): 154–9.
Kornasoff D, Frerick H, Bowdler J, et al. Aceclofenac is a well-tolerated alternative
to Naproxen in the treatment of Osteoarthritis. Clin Rheumatol 1997; 16 (1): 32–8.

20. Prospective, controlled, randomized, parallel double-blind
clinical trial.
Aceclofenac showed significant improvements from baseline
after 15 days, for both Osteoarthritis Severity Index (OSI) and VAS
(p<0.001) as well as for knee function, (p<0.01) which were
sustained for the 6-month study period.
DESCRIPTION
PATIENTS
OBJECTIVE
RESULTS
Similar efficacy to Diclofenac in Osteoarthritis
EFFICACY DATA
To assess the efficacy and tolerability of Aceclofenac in
comparison to Diclofenac in the treatment of Knee Osteoarthritis.
170 patients affected by Osteoarthritis were included
in the Aceclofenac group (100mg bid) and 165 patients
in the Diclofenac group (50mg tid) for 6 months.
Diaz C, Rodriguez 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.

21. Similar efficacy to Diclofenac in Osteoarthritis
Mean percentage of Osteoarthritis Severity Index.
Diaz C, Rodriguez 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.
100Percentage(OSI)
80
60
40
Baseline 0,5 1 2 3 4 5 6 months
Time
Aceclofenac (n=170)
Diclofenac (n=165)
*p<0.001 vs baseline
*
*
* * *
*
*
*
*
*
* * *
*
EFFICACY DATA

22. Diclofenac
Indomethacin
Ketoprofen
EFFICACY DATA
Proven efficacy in Rheumatoid Arthritis
In Rheumatoid Arthritis, similar efficacy to
Tenoxicam

23. Martín-Mola E, Gijón-Baños J, Ansoleaga JJ. Aceclofenac in comparison to
Ketoprofen in the treatment of Rheumatoid Arthritis. Rheumatol Int 1995;
15: 111–16.
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.
Proven efficacy in Rheumatoid Arthritis: key publications
EFFICACY DATA
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: 305–15.
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; 15 (5): 473–7.

24. To investigate the efficacy and safety of Aceclofenac in comparison
with Diclofenac in patients with active Rheumatoid Arthritis.
Long-term multicenter, double-blind, parallel group study.
Both treatment groups showed significant improvement from
baseline in evaluations of pain (VAS) and inflammation (Ritchie
Index) and a reduction in morning stiffness. There were no
significant differences between the groups. However, a trend towards
greater improvement in hand grip strength with Aceclofenac
(22% improvement vs. 17% with Diclofenac) was found.
DESCRIPTION
PATIENTS
OBJECTIVE
RESULTS
Similar efficacy to Diclofenac in Rheumatoid Arthritis
EFFICACY DATA
131 patients affected by Rheumatoid Arthritis were analysed
in the Aceclofenac group (100mg bid) and 130 patients in the
Diclofenac group (50mg tid) for 6 months.
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: 305–15.

25. 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: 305–15.
RitchieIndex(meanvalues)
Baseline
Time
Aceclofenac (n=131)
Diclofenac (n=130)
*p<0.01vs. Baseline
Similar efficacy to Diclofenac in Rheumatoid Arthritis
20
18
16
14
12
10
22
0.5 1 2 4 6 months
24
*
*
*
*
*
*
*
*
*
*
Improvement in the Ritchie Index. Assessment
of joint inflammation
EFFICACY DATA

26. Indomethacin
Tenoxicam
Naproxen
EFFICACY DATA
Proven efficacy in Ankylosing Spondylitis
In Ankylosing Spondylitis, Similar efficacy to

27. Proven efficacy in Ankylosing Spondylitis: key publications
EFFICACY DATA
Pasero G, Ruju G, Marcolongo R, et al. Aceclofenac vs. Naproxen in the treatment
of Ankylosing Spondylitis: a double-blind, controlled study. Curr Ther Res Clin
Exp 1994; 55: 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 1996; 23 (7): 1200–6. Abstract.
Villa Alcázar LF, Álvarez de Buergo M, Rico Lenza H, et al. Aceclofenac is as safe
and effective as Tenoxicam in the treatment of Ankylosing Spondylitis: a 3 month
multicentre comparative trial. J Rheumatol 1996; 27 (7): 1194-9.

28. Similar efficacy to Naproxen in Ankylosing Spondylitis
EFFICACY DATA
To compare the efficacy and tolerability of Aceclofenac and Naproxen in the
treatment of Ankylosing Spondylitis. Efficacy was evaluated using a visual
analogue scale for spontaneous pain, a scale for pain on movement and at
rest, and measurements of chest expansion, hand-to-floor distance, Schober’s
test and normal daily activities.
Double-blind, multicenter, controlled study.
Both drugs provided effective analgesia and a corresponding
improvement in functional activity. Overall efficacy assessment
was not significantly different between both groups.
60 patients with Ankylosing Spondylitis were included
in the Aceclofenac group (100mg bid) and 66 patients in the
Naproxen group (500mg bid) for 3 months.
DESCRIPTION
PATIENTS
OBJECTIVE
RESULTS
Pasero G, Ruju G, Marcolongo R, et al. Aceclofenac vs. Naproxen in the treatment of Ankylosing
Spondylitis : a double-blind, controlled study. Curr Ther Res Clin Exp 1994; 55: 833–42.

29. Similar efficacy to Naproxen in Ankylosing Spondylitis
Reduction in pain scores after 3 months
Pasero G, Ruju G, Marcolongo R, et al. Aceclofenac vs. Naproxen in the treatment of Ankylosing
Spondylitis : a double-blind, controlled study. Curr Ther Res Clin Exp 1994; 55: 833–42.
Meanspontaneouspainscore(VAS)
Baseline
Time
Aceclofenac (n=47)
Naproxen (n=57)
*p<0.01 vs. baseline
60
50
40
30
20
0.5 1 2 3 months
*
*
*
*
*
*
*
*
EFFICACY DATA

30. ACUTE
DISORDERS

31. VIRAL PHARYNGOTONSILLITIS
LOW BACK PAIN
ODONTALGIA
DYSMENORRHOEA
ACUTE DISEASES
POST- SURGICAL PAIN
MINOR MUSCULOSKELETAL INJURY

32. 35
Superior efficacy to Diclofenac in Low Back Pain
EFFICACY DATA
To evaluate the clinical analgesic effect (change in pain
assessed by VAS score) in patients affected by Low
Back Pain.
Multi-center, double blind, randomized clinical trial.
Aceclofenac is not inferior to Diclofenac resinate in analgesic
efficacy and a trend towards a better safety and tolerability profile
was found.
114 patients affected by Low Back Pain were studied
in the Aceclofenac group (100mg bid) and 113 patients in the
Indomethacin group (75mg bid) for 10 days.
DESCRIPTION
PATIENTS
OBJECTIVE
RESULTS
Schattenkirchner M, Milachowski KA. A double blind, multicentre, randomised clinical trial comparing the efficacy
and tolerability of Aceclofenac with Diclofenac resinate in patients with acute Low Back Pain. Clin
Rheum 2003;22:127-35.

33. 36
Superior efficacy to Diclofenac in Low Back Pain
Mean changes in pain scores at rest at visit 3
Painscores
(VASmeanvaluesinmm)
ITT Population
–53
Schattenkirchner M, Milachowski KA. A double blind, multicentre, randomised clinical trial comparing the efficacy
and tolerability of Aceclofenac with Diclofenac resinate in patients with acute Low Back Pain. Clin
Rheum 2003;22:127-35.
–54
–55
–56
–57
–58
–59
–60
–61
–62
–63
PP PopulationITT Population
ACF (n=114) DCF (n=113) ACF (n=100) DCF (n=105)
EFFICACY DATA

34. 37
BRISTAFLAM
SAFETY DATA

35. Multicentre, case-control study.
Among all NSAIDs included in the primary analysis, Aceclofenac was associated
with a low risk of UGIB, while Meloxicam and Rofecoxib were associated with
a medium risk.
The results do not confirm that greater selectivity for COX-2 confers less risk of
Upper Gastrointestinal Bleeding.
DESCRIPTION
PATIENTS
OBJECTIVE
RESULTS
A low rate of Upper Gastrointestinal Bleeding (UGIB)
SAFETY DATA
All incident community cases of upper gastrointestinal bleeding from gastric or
duodenal lesion in patients aged >18 years of age (4,309 cases). After secondary
exclusions, 2,813 cases and 7,193 matched controls were included in the analysis.
Setting: 18 hospitals in Spain and Italy with total study experience of 10,734,897
person-years.
To estimate the risk of UGIB associated with the use of analgesics and NSAIDs.
Laporte J.R., Ibáñez L., Vidal X. et al. Upper Gastro-Intestinal Bleeding associated with the use of NSAIDs
New vs. Older Agents. Drug Safety 2004; 27(6): 411-20.

36. A low rate of Upper Gastrointestinal Bleeding (UGIB)
25
20
15
10
5
0
Laporte J.R., Ibáñez L., Vidal X. et al. Upper Gastro-Intestinal Bleeding associated with the use of NSAIDs
New vs. Older Agents. Drug Safety 2004; 27(6): 411-20.
Oddsratios
Risk of UGIB with NSAIDs taken the week
before the Index Day*
SAFETY DATA
1,4
3,1 3,2 3,7
4.9 5,7
7,2 8,0
10,010,0 10,0
15.5
16,6
24,7
Aceclofenac
Ibuprofen
Nimesulide
Diclofenac
Dexketoprofen
Meloxicam
Rofecoxib
Aspirin(A.acid)
Indomethacin
Naproxen
Ketoprofen
Piroxicam
NSAID+anti-Pl.
Ketorolac
* Index day: the day on which the upper gastrointestinal bleeding started

37. 40
An open-label, multicenter, observational surveillance study complying
with the Safety Assessment of Marketed Medicines (SAMM) guidelines.
Adverse events (p<0.001), gastrointestinal adverse events (p<0.001)
and patients withdrawing from treatment (p<0.001) were significantly
less common with Aceclofenac than with Diclofenac.
DESCRIPTION
PATIENTS
OBJECTIVE
RESULTS
Better gastrointestinal tolerability than Diclofenac
in Rheumatic Diseases
SAFETY DATA
7,890 patients affected by rheumatic diseases were included
in the Aceclofenac group (100mg bid) and 2,252 patients in the
Diclofenac group (75mg bid) for 12 months.
To investigate the safety and tolerance of Aceclofenac and Diclofenac in
patients with Rheumatic Diseases in normal clinical practice.
Huskisson E, Irani M, Murray F. A large prospective open-label, multicentre SAMM study, comparing the safety of Aceclofenac
in patients with Rheumatic Disease. Eur J Rheumatol Inflamm 2000; 17 (1):1-7.

38. 41
20
Aceclofenac vs. Diclofenac : AEs and withdrawals
Huskisson E, Irani M, Murray F. A large prospective open-label, multicentre SAMM study, comparing the safety of Aceclofenac
in patients with Rheumatic Disease. Eur J Rheumatol Inflamm 2000 ; 17 (1):1-7.
Percentages
Adverse events
0
Discontinuation due
to adverse events
Aceclofenac n= 7890
Diclofenac n= 2252
* p<0.001 vs. Diclofenac
5
15
10
30
25
*
*
*
GI adverse events
Better gastrointestinal tolerability than Diclofenac
in Rheumatic Diseases
SAFETY DATA

39. 42
4
Aceclofenac vs. Diclofenac: adverse events ≥ 1%
Huskisson E, Irani M, Murray F. A large prospective open-label, multicentre SAMM study, comparing the safety of Aceclofenac
in patients with Rheumatic Disease. Eur J Rheumatol Inflamm 2000;1 7 (1):1-7.
Percentages
Dyspepsia
0
Diarrhoea
Aceclofenac n= 7890
Diclofenac n= 2252
* p=0.017 vs. Diclofenac ** p=0.01 vs. Diclofenac *** p<0.001 vs. Diclofenac
1
3
2
6
5
Abdominal pain
***
*** **
*
Nausea
Better gastrointestinal tolerability than Diclofenac
in Rheumatic Diseases
SAFETY DATA

40. CONCLUSIONS
Bristaflam

41. Aceclofenac is as effective or even more effective
than classic NSAIDs, as confirmed by clinical trials and in dail
clinical practice (over 12 years)
Better gastrointestinal safety profile than gold standard NSAID
Its efficacy and tolerability make for higher levels of treatment
compliance
CONCLUSIONS
Aceclofenac has extensive experience worldwide

42. A GLOBAL BRAND
Thank you for your attention!!
Bristaflam