CURRICULUM VITAE

Dr.dr LOLA
LOLA SUSIANTI
SUSIANTI, SpPD-FINASIM
SpPD-FINASIM

TEMPAT /TGL LAHIR:

BUKITTINGGI, 18 SEPT 1974

RIWAYAT PENDIDIKAN
DR UMUM FK UNAND 2000
SP PENYAKIT DALAM FK UNAND 2014

TEMPAT TUGAS : RSUD AHMAD RIPIN

RS MMC
RS BAITURRAHIM
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TATALAKSANA NYERI KRONIS

dr LOLA SUSIANTI SpPD-FINASIM

 What is Pain?
Definisi Pain menurut IASP
(International Association For The Study Pain)

“Rasa nyeri didefinisikan sebagai

pengalaman sensori dan pengalaman
emosional yang tidak menyenangkan
yang dikaitkan dengan kerusakan atau
potensial kerusakan jaringan”
.
 PAIN

nociceptive acute
PAIN
neuropathic chronic
Nociceptive vs Neuropathic Pain
Nociceptive Mixed Type Neuropathic
Pain Caused by a Pain
combination of both
Disebabkan oleh Dipicu oleh lesi primer
primary injury and
aktivitas pada neural atau disfungsi sistim
secondary effects
patway sebagai respon syaraf
menanggapi
rangsangan berpotensi
merusak jaringan CRPS*
Postherpetic
Postoperative Trigeminal
neuralgia
pain Arthritis neuralgia

Sickle cell Neuropathic

Mechanical crisis low back pain Central post-
low back pain
stroke pain
Distal
Sports/exercise polyneuropathy
injuries (eg, diabetic, HIV)
*Complex regional pain syndrome

National Initiative on Pain Control, 2005

 Pain Management
PHARMACOLOGIC :
Analgesics broadly divided into :
• Non Opioid
- Paracetamol
- NSAIDs : COX -2 (ex: Etoricoxib), t-NSAIDs
• Opioid : Tramadol, Tapentadol, Morphin
• Adjuvant : Antidepressants, Anticonvulsans Corticosteroid, Local
anaesthetic etc

NON PHARMACOLOGIC
 Mechanism of Action of NSAIDs
Normal condition Inflammation
Arachidonic acid
COX-1 COX-2
(constitutive) X T-NSAIDs X (inducible)
(

PGH2 PGH2

PGE2 PGI2 TXA2 PGE2 PGI2 TXA2

Stomach Stomach Platelets Synovial membrane,

Kidney Kidney endothelium, vascular smooth
Brain Endothelium muscle, WBCs, brain

• GI protection
• vasodilation • inflammation
• renal perfusion
• pain
• fever
• inhibit platelet aggregation

NSAID=nonsteroidal anti-inflammatory drug; COX=cyclooxygenase. Adapted from Wallace JL. Am J Med. 1999;107(6A):11S–17S; Hinz B, et al. J Pharmacol Exp Ther. 2002;300(2):367–375;
IS
Vanegas H, et al.; Prog Neurobiol. 2001;64(4):327–363; Furst DE. Am J Med. 1999;107(6A):18S–26S; 7 Ther.
Vane JR, et al. Annu Rev Pharmacol Toxicol. 1998;38:97–120; Fung HB, et al. Clin
1999;21(7):1131–1157.
 Less GI side effects
More GI side effects
Diclofenac Etoricoxib
Acetosal Indomethacin Ibuprofen
Ketorolac Piroxicam Ketoprofen
Meloxicam COXIB
Celecoxib
Nimesulide Valdecoxib

preferentially non- preferentially

COX-1 COX-1 COX-2 COX-2
selective
selective selective selective selective
COX
inhibitor inhibitor inhibitor inhibitor
inhibitor

anti-inflammatory
analgesic
 Etoricoxib
Etoricoxib is a second generation coxib/selective COX-2.

Felden L er al, Pharm Res 2014

 Etoricoxib showed 24 minutes Fast Onset of action
& 24 hours Long Last
Pain Relief Score* Over 24 Hours
Etoricoxib 120 mg had a 24-Minute onset of action**
(Dose ranging study)
3.5
3.0
Mean PR score (±SE)*

Etoricoxib 180 mg (n=74)

2.5 Etoricoxib 120 mg (n=76)
Etoricoxib 240 mg (n=76)
2.0 Etoricoxib 60 mg (n=75)
1.5
Ibuprofen 400 mg (n=47)
1.0
Placebo (n=49)
0.5
0.0
0 1 2 3 4 5 6 7 8 12 24
Time (hour) postdose
• Etoricoxib 120 mg had a 24-minute or less onset of action in 50% of patients
• Etoricoxib 120 mg sustained a longer duration of action than ibuprofen
SE = standard error
p<0.001 for etoricoxib 60 and 120 mg and ibuprofen 400 mg vs. placebo over eight hours; p≤0.025 for etoricoxib 120 mg vs. ibuprofen 400 mg
over eight hours
Study included 60, 120, 180, and 240 mg dose for etoricoxib.
*Pain relief (PR) rated on a 0- to 4-point scale (0 = none, 1 = a little, 2 = some, 3 = a lot, 4 = complete); **Median time to onset in 50% of patients
Adapted from Malmstrom K et al. Clin Ther 2004;26:667-79
 Osteoarthritis
Hand OA

Knee OA with joint pain and crepitus

 Osteoarthritis
Masalah

Nyeri
Deformitas
Keterbatasan gerak
 NSAIDs in OA Recommendation

EULAR Recommendation for Osteoarthritis, 2009

Osteoarthritis
Dose-Ranging Study – WOMAC Pain Subscale*

Etoricoxib produced substantial pain relief similar to diclofenac

Part 1 Part 2 Extension
0
More
Etoricoxib 60 mg once daily (n=112)
pain
week 0 to 52
baseline in pain level

–10
Mean change from

Placebo (n=60) Diclofenac 50 mg three times daily

(n=102) week 8 to 52
–20

p<0.001
–30
p=NS

–40

–50 Less
pain
R 2 4 6 8 14 20 26 34 42 52

Placebo- Active-comparator–controlled
controlled
Weeks postrandomization
Re-randomization took place at week 6
NS = not significant
*0- to 100-mm visual analog scale (VAS) (0 = no pain to 100 = extreme pain)
Adapted from Gottesdiener K et al Rheumatology 2002;41:1052–1061; Curtis S et al. Poster presented at EULAR, 2001.
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 Rheumatoid Arthritis

Rheumatoid
Severe joint erosions nodul
causes joint deformities
EULAR = European League Againts Reumatism

Smolen JS, et al. Ann Rheum Dis 2017;0:1-18

Smolen JS, et al. Ann Rheum Dis 2017;0:1-18
EULAR = European League Againts Reumatism
Smolen JS, et al. Ann Rheum Dis 2017;0:1-18
Etoricoxib 90 mg once daily lebih efektif dibandingkan
placebo dan setara dengan Naproxen 500 mg dua kali
sehari pada pasien RA selama 12 minggu.
Dosis Etoricoxib lebih praktis
ETORICOXIB masuk Guideline ACR Level A th. 2012

Pada Guideline American College of Rheumatology

2012, Etoricoxib (level A) dapat diberikan pada pasien
Gout Artritis Akut dibandingkan Celecoxib (level B)
MEDAL PROGRAM

Unsurpassed safety
profile of Etoricoxib :
- Better GI safety
- Comparable CV
safety
 MEDAL Program: Confirmed
Upper GI Events
3.0
Etoricoxib 60 and 90 mg pooled (176 events)
Diclofenac 150 mg (246 events) All confirmed
2.5
eventsa
Cumulative Incidence,

Etoricoxib vs diclofenac
HR=0.69 (95% CI: 0.57, 0.83) P=0.0001
2.0
% (95% CI)

1.5

1.0 Complicated
events
P=0.561
0.5
Etoricoxib vs diclofenac
HR=0.91 (95% CI: 0.67, 1.24)
0
0 6 12 18 24 30 36 42
Months
Patients at risk for upper GI events, no.
Etoricoxib 17,412 13,704 10,972 8400 6509 4063 821
Diclofenac 17,289 13,190 10,396 8027 6306 3867 820

GI=gastrointestinal; ITT=intention-to-treat; CI=confidence interval; HR=hazard ratio.

aThese included uncomplicated (perforation, ulcer, and bleeds) and complicated (perforation, obstruction, and bleeds) events.
Adapted from Laine L, et al. Lancet. 2007;369:465–473; Cannon CP, et al. Lancet. 2006;368:1771–1781.
 MEDAL Study: Discontinuations Due
to Clinical or Laboratory GI AEsa

P<0.001b Etoricoxib
20 Diclofenac 150 mg
17.13

15
Rate/100 PY

P<0.001b P<0.001b

10 8.61 8.69 9.13

3.96 4.41
5

0
60 mg/d vs 90 mg/d vs 90 mg/d vs
Diclofenac Diclofenac Diclofenac
Patients With OA Patients With RA

GI=gastrointestinal; AEs=adverse events; mITT=modified intention-to-treat; PY=patient-years; OA=osteoarthritis; RA=rheumatoid arthritis;

COX=cyclooxygenase.
aEvents within 1 year of treatment; bFor both COX proportion hazard and stratified log-rank test.
 BIOEQUIVALENCE OF ORINOX

BIOEKUIVALENCE = THERAPEUTIC EQUIVALENCE

ORINOX bioekuivalen dengan originator: EFIKASI,
KEAMANAN, dan KUALITAS setara dengan originator

Aaroon S Kesselheim, JAMA 2008;300(21) 2514-2526

 ORINOX BIOEKUIVALEN VS ORIGINATOR
Mean plasma concentration-time profiles of etoricoxib in human subjects (n = 27) after a
single dose oral administration etoricoxib tablets produced by PT Dexa Medica (Test drug)
- ORINOX and the reference (Reference drug = Originator) : COMPARABLE / SIMILAR
 ORINOX BIOEKUIVALEN vs ORIGINATOR

Putri, RSI et al. 2016. Summary Report of Bioequivalence Study. Data on file
 KESIMPILAN
• NSAID termasuk COX2 inhibitor adalah obat
yg paling sering digunakan untuk nyeri kronis
pada OA dan RA.
• Etoricoxib menunjukkan efikasi yg sebanding
dg NSAID konvensional pada kasus OA danRA
• Etoricoxib (Orinox) mempunyai efek samping
GI paling rendah

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