Presentasi ini tentang obat nyeri yang aman untuk lambung, selain itu obat ini tidak mengganggu pembekuan darah. Parecoxib adalah jenis analgetik cox2. Penggunaan untuk pasien dengan kelainan jantung dan pada penderita kelainan ginjal harus hati-hati.

1. The essential use ofThe essential use of ParecoxibParecoxib inin
multimodal post-operative painmultimodal post-operative pain
managementmanagement
Presenter
Place & Date

2. PROBLEM IN POST-OPERATIVEPROBLEM IN POST-OPERATIVE
PAIN MANAGEMENTPAIN MANAGEMENT

3. What is PAIN?What is PAIN?
PAIN is described as:
An unpleasant sensory and emotional
experience associated with actual or
potential tissue damage, or described in
terms of such damage
 International Association for the Study of
Pain (IASP) 1994*
* Merskey H et al. (Eds) In: Classification of Chronic Pain: Descriptions of Chronic Pain Syndromes and Definitions of Pain Terms. 1994:209-212.

4. Why is it IMPORTANTWhy is it IMPORTANT
to treat PAIN?to treat PAIN?
 Pain is the most common reason
patients seek medical attention1
 Each year, between 15% and 20% of
the US population experiences acute
pain2
 Have we managed post-operative pain
OPTIMALLY?
1. Coda BA et al. Bonica’s Management of Pain. 2001:222-40
2. Bonica JJ et al. Bonica’s Management of Pain. 2001:3-16.

5. Post-operative pain remainsPost-operative pain remains
MAJOR PROBLEM in USMAJOR PROBLEM in US
73 MILLIONS surgical patients
each year in US
80% experience acute post-operative pain
20% experience SEVERE PAIN!
Hutchison RW. Am J Health-Syst Pharm 2007;64:2-5.

6. Current post-operative pain
management is SUB-OPTIMAL
Any pain Slight
pain
Moderate
pain
Severe
pain
Extreme
pain
Patient’s worst painPatient’s worst pain
0
10
20
30
40
50
60
70
80
90
100
Patients (%)
19931
77
19
49
23
8
83
13
47
21 18
20032
1. Warfield & Kahn. Anesthesiology 1995;83:1090
2. Apfelbaum et al. Anesth Analg 2003;97:534
3. Berry PH, Dahl JL. Pain Manag Nurs 2000;1(1):3-12
These figures have BARELY CHANGED since the 1950s!3

7. Cost of Pain ManagementCost of Pain Management
Medical expenses1
◦ Prolonged hospitalization
◦ Increased hospital resource utilization2
Lost income and reduced productivity1
Quality of life3
◦ Impaired activities of daily living
◦ Mood changes
◦ Decreased involvement in activities
1
Coda BA et al. Bonica’s Management of Pain. 2001:222-240.
2
Zimberg SE. Reducing pain and costs with innovative postoperative pain management. Manag Care Q. 2003;11:34-36.
3
Won A et al. J Am Geriatr Soc. 1999;47:936-942.

8. Examples
• Pain due to inflammation
• Limb pain after a fracture
• Joint pain in osteoarthritis
• Postoperative visceral pain
Common descriptors2
• Aching
• Sharp
• Throbbing
Mixed Pain
Pain with
neuropathic and
nociceptive
components
Neuropathic Pain
Pain initiated or caused by a
primary lesion or dysfunction
in the nervous system
(either peripheral or central
nervous system)1
Inflammatory Pain
Pain caused by injury to
body tissues
(musculoskeletal,
cutaneous or visceral)2
Mechanism Based ClassificationMechanism Based Classification
Including post-
operative pain
1. International Association for the Study of Pain. IASP Pain Terminology.
2. Raja et al. in Wall PD, Melzack R (Eds). Textbook of pain. 4th Ed. 1999.;11-57

9. The Continuum of PainThe Continuum of Pain11
<1 month
Time to resolution
≥3-6 months
Acute
Pain
Chronic
Pain
•Usually obvious tissue damage
•Increased nervous system
activity
•Pain resolves upon healing
•Serves a protective function
•Pain for 3-6 months or
more2
•Pain beyond expected
period of healing2
•Usually has no protective
function3
•Degrades health and
function3
1. Cole BE. Hosp Physician. 2002;38:23-30.
2. Turk and Okifuji. Bonica’s Management of Pain.
2001.
3. Chapman and Stillman. Pain and Touch. 1996.
Insult
Including post-operative pain

10. Activation of the Central
Nervous System
at the Spinal Cord
Level
T Tissue Damage due
to incision
Activation of the
Peripheral Nervous
System
Transmission of the Pain
Signal to the Brain
Pain
Pain ResponsePain Response
Samad TA et al. Nature. 2001;410:471-5.
In surgical setting

11. NociceptionNociception
SpinothalamicSpinothalamic
tracttract
PeripheralPeripheral
nervenerve
Dorsal HornDorsal Horn
Dorsal rootDorsal root
ganglionganglion
PainPain
Modulation
Transduction
AscendingAscending
inputinput
DescendingDescending
modulationmodulation
PeripheralPeripheral
nociceptorsnociceptors
TraumaTrauma
Adapted from Gottschalk A et al. Am Fam Physician. 2001;63:1981, and Kehlet H et al. Anesth Analg. 1993;77:1049.
Perception
Transmission

12. Arachidonic Acid HypothesisArachidonic Acid Hypothesis
Arachidonic Acid
COX-1 COX-2
Body Homeostasis
•Gastric integrity
•Renal function
•Platelet function
Inflammation
Pain
Needleman P. et al. J Rheumatol 1997;24(suppl 49):6
Fitzgerald GA et al. N Engl J Med 2001;345:433-42
Cyclooxygenase
(COX)
Nonselective
NSAID
COX-2
selective
InhibitorX XX

13. PARECOXIBPARECOXIB
Efficacy

14. aa
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1
Hubbard RC et al. Anesthesiology. 2001;95:A807.
2Data on file. Clinical Study 020. July 31, 2000. Pfizer, Inc., New York, NY.
Parecoxib sodium for injection: Single-dose efficacy mean score (less to more
relief) vs morphine and ketorolac following total hip replacement surgery1,2
Measured as Time-Specific Pain Intensity Difference (Categorical)
*P <.05 statistically significantly
different from morphine 4 mg.
• Most patients (58%) were older than 65 years2
DYNASTAT 40 mg IV (n=44)
ketorolac 15 mg IV (n=40)
morphine 4 mg IV (n=38)
PainIntensityDifference(Mean)
lessreliefmorerelief
1.6
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0.0
-0.2
0 1 2 3 4 5 6 7 8 10 12
*
*
*
*
*
*
*
*
*
*
Hours Postdose
DYNASTAT 40 mg IV (n=44)
ketorolac 15 mg IV (n=40)
morphine 4 mg IV (n=38)
DYNASTAT 40 mg IV (n=44)
ketorolac 15 mg IV (n=40)
morphine 4 mg IV (n=38)
PainIntensityDifference(Mean)
lessreliefmorerelief
1.6
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0.0
-0.2
0 1 2 3 4 5 6 7 8 10 12
*
*
*
*
*
*
*
*
*
*
0 1 2 3 4 5 6 7 8 10 12
*
*
*
*
*
*
*
*
*
*
Hours Postdose

15. Postoperative Efficacy in Orthopedic Surgery:Postoperative Efficacy in Orthopedic Surgery:
Powerful, Lasting Pain ReliefPowerful, Lasting Pain Relief
Measured as Time-Specific Pain Intensity Difference (Categorical)
Adapted from Rasmussen GL et al. Am J Orthop. 2002;31:339.
Parecoxib sodium for injection: Single-dose efficacy mean score (less to more
relief) vs morphine and ketorolac following total knee replacement surgery1
*P<.05 statistically significantly
different from morphine 4 mg.
1.6
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0.0
-0.2
Hours Postdose
PainIntensityDifference(Mean)
lessreliefmorerelief
DYNASTAT 40 mg IV (n=42)
ketorolac 30 mg IV (n=42)
morphine 4 mg IV (n=42)
placebo (n=39)
*
*
0 1 2 3 4 5 6 7 8 10 12
*
*
*
*
*
*
*
*
*
*
*P<.05 statistically significantly
different from morphine 4 mg.
1.6
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0.0
-0.2
Hours Postdose
PainIntensityDifference(Mean)
lessreliefmorerelief
DYNASTAT 40 mg IV (n=42)
ketorolac 30 mg IV (n=42)
morphine 4 mg IV (n=42)
placebo (n=39)
*
*
0 1 2 3 4 5 6 7 8 10 12
*
*
*
*
*
*
*
*
*
*

16. Postoperative Efficacy in LaparotomyPostoperative Efficacy in Laparotomy
1
Barton SF, et al. Anesthesiology. 2002;97:310.
Parecoxib sodium for injection : Single-dose efficacy mean
score (less to more relief) vs morphine and ketorolac1
*P<.05 vs morphine 4 mg IV.
PainIntensityDifference(Mean)
lessreliefmorerelief
Hours Postdose
-0.4
-0.2
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
0.25 0.5 0.75 1 1.5 2 3 4 5 6 7 8 10 12 16 240
* * *
*
*
*
*
* *
parecoxib sodium40
mg IV (n=38)
ketorolac 30 mg IV
(n=41)
morphine 4 mg IV
(n=42)
placebo (n=42)

17. Bikhazi GB, Snabes MS, Bajwa ZH, et al. Am J Obstet Gynecol 2004; 191 : 1183 - 91
Fast Onset:
Relieving Pain as early as 3 minutes

18. Comparison: onset of actionComparison: onset of action
Parecoxib
sodium1
40 mg
Ketorolac
tromethamine2
30 mg
Dexketoprofen
trometamol3
50 mg
Earliest 3 minutes 5 minutes 30 minutes
Median 7 minutes 10 minutes 45 minutes
1. Bikhazi GB, Snabes MS, Bajwa ZH, et al. Am J Obstet Gynecol 2004; 191 : 1183 – 91
2. Zhou TJ et al. Anesth Analg 2001;92:1569 –75
3. Sanchez-Carpena J et al. Eur J Clin Pharmacol 2007;63:751–760

19. PARECOXIBPARECOXIB
The Important Safety Profile

20. No Significant Effect on Platelet AggregationNo Significant Effect on Platelet Aggregation
with parecoxibwith parecoxib
II
No statistically significant difference in effect on platelet aggregation between parecoxib sodiumand placebo.
1
Noveck RJ et al. Clin Drug Invest. 2001;21:465-476.
2
Data on file. Clinical Study 027. February 25, 2000. Pfizer Inc., New York, NY.
Parecoxib : % Platelet aggregation response
(mean) to arachldonate vs ketorolac§
in healthy adults1,2
parecoxib sodium40 mg bid IV (n=15)
ketorolac§
30 mg qid IV (n=15)
placebo (n=15)
*P<.001 for ketorolac
vs placebo.
PlateletAggregation
Percentage(Mean)
0
20
40
60
80
100
Baseline Predose 2 Hr 4 Hr 6 Hr
* * * *
Day 8
II II
IIII
Reduce prolonged bleeding risk

21. No Effect on Bleeding Time with parecoxibNo Effect on Bleeding Time with parecoxib
IlNo statistically significant difference in effect on bleeding time between parecoxib sodiumand placebo.
¶
Mean of bleeding time determination at 2, 4, and 6 hours on each dose day.
1
Noveck RJ et al. Clin Drug Invest. 2001;21:465-476.
2
Data on file. Integrated Summary of Safety Information. August 26, 2000. Pfizer Inc., New York, NY.
parecoxib : Multidose platelet effect (bleeding time mean change from baseline
[sec]) vs ketorolac§
and placebo in healthy adults1,2II
*P<.05 vs
ketorolac.2
**P<.05 vs
placebo.2
BleedingTimeMeanChangeFrom
Baseline(sec)¶
at2HoursPostdose
200
175
150
125
100
75
50
25
0
placebo
First
Dose
Day
Final
Dose
Day
First
Dose
Day
Final
Dose
Day
First
Dose
Day
Final
Dose
Day
**
parecoxib
40 mg IV bid
ketorolac
30 mg IV qid
*

22. Endoscopically Detected Upper GI Ulceration wasEndoscopically Detected Upper GI Ulceration was
Significantly Lower with parecoxib than withSignificantly Lower with parecoxib than with
Nonselective NSAIDsNonselective NSAIDs
The correlation between findings of endoscopic studies, and the relative incidence of clinically significant serious upper GI events has not been established.
1
Stoltz RR et al. Am J Gastroenterol. 2002;97:65-7.
2
Harris SI et al. J Clin Gastroenterol. 2004;38:575–580.
3
Data on file. parecoxib sodiumIntegrated Summary of Safety Information. August 26, 2000. Pfizer Inc., New York, NY.
40
20
0
parecoxib : Multidose safety (gastroduodenal ulceration)
vs ketorolac* and naproxen in healthy adults (pooled data from 3 7-day studies)1-3
§
P<.05 vs placebo.
II
P≤.05 vs parecoxib sodium40 mg
bid.
¶
P≤.05 vs parecoxib sodium20 mg
bid.
PatientsWithEndoscopically
DetectedUlceration(%)
placebo parecoxib parecoxib ketorolac ketorolac naproxen
20 mg IV bid 40 mg IV bid 15 mg IV qid§II
30 mg IV qid§II¶
500 mg
PO bid§¶
0/115
1/42
7/31
2% 0%
23%
33%
17%
27/81
7/41
0/70
0%

23. IMS Indonesia. www.mims.com. Accessed on 10/12/2010

24. SAFETY PROFILE IN SPECIAL POPULATIONSAFETY PROFILE IN SPECIAL POPULATION
Parecoxib1
Ketorolac
tromethamine2
Dexketoprofen
trometamol2
Elderly No dosage
adjustment
Minimum dose Minimum dose
Hepatic
impairment
No dosage
adjustment for
mild hepatic
impairment
(no information) Reduced dose
for mild to
moderate
impairment
Renal
impairment
No dosage
adjustment for
mild to severe
renal impairment
Reduced dose
for mild
impairment
Reduced dose
for mild
impairment
BPOM Approval 2009
MIMS Indonesia. www.mims.com. Accessed on 10/12/2010

25. PARECOXIBPARECOXIB
Multimodal Pain ManagementMultimodal Pain Management

26. Multimodal Therapy Can ProvideMultimodal Therapy Can Provide
Enhanced AnalgesiaEnhanced Analgesia
1
Crews JC. JAMA. 2002;288:629-632.
2
Samad TA et al. Trends Mol Med. 2002;8:390-396.
3
Atcheson R et al. Management of Acute and Chronic Pain. London, England: BMJ Books; 1998:23-50.

27. Disadvantages of Opioid TherapyDisadvantages of Opioid Therapy
There are numerous potential drawbacks to
postoperative opioid therapy1,2
:
◦ Complications (eg, respiratory depression,
nausea/vomiting/ileus)
◦ Slower recovery
◦ Potential for abuse
◦ Possible inadequacy at controlling pain on
movement
1
Atcheson R et al. Management of Acute and Chronic Pain. 1998:23-50.
2
Power I et al. Surg Clin North Am. 1999;79:275-295.

28. Parecoxib Reduced Opioid ConsumptionParecoxib Reduced Opioid Consumption
1
Hubbard RC et al. Br J Anaesth. 2003;90:166-172.
2
Wender RH et al. ASRM. 2001.
3
Malan TP Jr et al. Anesthesiology. 2003;98:950-956.
Orthopedic
(total knee
replacement)
(n=128)1
Gynecologic
(abdominal
hysterectomy)
(n=24)2
Orthopedic
(total hip
replacement)
(n=120)3
28%
reduction
39%
reduction
36%
reduction
P≤.05 vs placebo in all 3 studies
parecoxib 40 mg IV: Reduction in patient-controlled
analgesia (PCA) opioid vs placebo at 24 hours after first
dose of parecoxib sodium1-3

29. Conclusion:
“Parecoxib improves postoperative
analgesia, reduces the dose of
morphine required by patients, and
does not increase perioperative
bleeding. The analgesic effects are still
evident at 24 h when two injections,
spaced 12 h apart, are given.”
(Martinez V et al. 2007 – No
financial support of Pfizer)
Martinez V et al. Anesth Analg 2007;104:1521–7
UPDATE!

30. THANK YOUTHANK YOU