OXYCODONE :

SHARING EXPERTISE AND

CLINICAL PRACTICE

A.M.TAKDIR MUSBA

DEPARTMENT OF ANESTESHIOLOGY, INTENSIVE CARE AND PAIN MANAGEMENT

FACULTY OF MEDICINE, HASANUDDIN UNIVERSITY, MAKASSAR

INDONESIAN SOCIETY OF ANESTHESIOLOGY FOR PAIN MANAGEMENT ( ISAPM )

PERDATIN INDONESIA
OUTLINE

 OXYCODONE : OLD “NEW” DRUG

 PK/PD CONSIDERATION
 EVIDENCE-BASED of OXYCODONE
 CLINICAL APPLICATION : focused on
Postoperative Analgesia
OXYCODONE

 Clinical practice in 1917

 Phenantrene alkaloid : transformation from
thebaine  semi-synthetic opioid
 A Strong opioid
 Replace Morphine as the first choice opioid in
several countries
 Closely resembles Morphine with some
differences ( Pk profiles )
 Widely use for acute and cancer pain
 Safe and effective opioid analgesia
Safe and effective as an
opioid analgesia

 Greater pain control

 Fewer severe adverse event
 Faster onset of action
 Longer duration

No best drugs but the best doctors

• Pk/Pd
• Clinical apllication
 PHARMACODYNAMICS of OXYCODONE
 Oxycodone (6-deoxy-7,8-
dehydro-14- hydroxy-3-O-
methyl-6-oxomorphine)
 μ-opioid receptor specific ligand
with clear agonist properties
 μ-opioid receptor binding affinity :
 Less than morphine
 Oxymorphone : higher affinity
 Antinociceptive effects of
oxycodone could be κ-opioid
receptor–mediated
 PHARMACOKINETICS of OXYCODONE

 O-demethylation  Oxymorphone
 N-demethylation  Noroxycodone ( first-pass
metabolism )
 Catalyzed by CYP 2D6
 Bioavailibility of Oxycodone >60% vs Morphine 20%
 Liposolubility : Fentanyl > Oxycodone > Morphine
Pk Oxycodone CR,IRS,IM,IV
Drug and Dose Cmax Tmax (h) T1/2z (h) CL (L/min)
(ng/mL)
CR Oxycodone 20 mg 18.6 + 6.1 2.6 + 1.1 8.0 +3.0

IRS Oxycodone 20 mg 41.6 + 6.1 1.3 + 0.6 3.2 + 0.9

IM Oxycodone 0.14 mg/kg 34 + 10 1.0 (0.5-1.0) 5.1 + 1.7

IV Oxycodone 0.07 mg/kg 2.3 ( 2-5.5) 0.78
IV Oxycodone 0.05 mg/kg 13 0.42 ( 0.33-4) 2.6 ( 2-3.1) 0.83
CR controlled-release; IRS immediate-release solution; IM intramuscular; IV intravenous; Cmax maximum
concentration; Tmax time to maximum concentration; T1/T2z elimination half life; CL clearance

Kidney Failure Liver Failure

• T1/2 prolonged to 3.9 hrs for iv • Cmax higher 40%
• T1/2 prolonged 1 hr for CR • T1/2z prolonged 2 hours

Kalso E., Journal of Pain and Symptom Management. Vol. 29. 2005
OXYCODONE as opioid analgesia
for postoperative pain

 Intravenous Oxycodone Vs Morphine

(0.05 mg/kgBW ) :
 Faster pain relief and lasted longer with oxycodone
than morphine
 Morphine caused more sedation and greater decreases
in the mean arterial blood pressure than oxycodone
 In other respects, the two opioids were comparable

Kalso E, Po¨yhia¨ R, Onnela P, et al. Intravenous morphine and oxycodone for pain
after abdominal surgery. Acta Anaesthesiol Scand 1991;35:642–646
 OXYCODONE as opioid analgesia
for postoperative pain
Intravenous Oxycodone Vs Fentanyl
 Fewer patients in the oxycodone group required the
opioid and shorter time needed to achieve pain
relief with oxycodone
 Postoperative VAS levels significantly lower in the
oxycodone in the PACU and on the ward (over a 24–
hours period)
 No significant differences in side effects
 Conclusions: Oxycodone was more effective than
fentanyl when administered on the basis of the
recommended dose ratio (1 : 100)
Seo, DK. Et al. A comparison of oxycodone and fentanyl in the management
of early postoperative pain and for patient-controlled analgesia after total abdominal hysterectomy.
Anesth Pain Med 2016; 11: 176-181
 Intravenous oxycodone a potentially
important "new" old drug for
postoperative pain control

 Comparing IV oxycodone to other IV opioids

for postsurgical pain
 Oxycodone is a safe and effective analgesic
 IV oxycodone may be associated with greater pain
control, fewer or less severe adverse events, and faster
onset of action
 Oxycodone has been reported to be safe in the geriatric
and other special populations when adequate clinical
adjustments are made
Pergolizzi JV Jr et al. Perspectives on Intravenous Oxycodone for Control of
Postoperative Pain. Pain Pract 2016 Sep;16(7):924-34.
Clinical application

 Intermittent intravenous injection

 Continuous intravenous infusion
 Patient Controlled Analgesia
Intermittent IV Opioid
Continuous intravenous opioid
Patient Controlled Analgesia
MEC and MEAC Opioid Oxycodone
 Loading dose of Oxycodone

Therefore, the loading dose of oxycodone administered at the end of surgery should
be 0.1 mg/kg, rather than 2 mg, to relieve immediate postoperative pain in the
postanesthetic care unit
Choi B.M., Korean Journal Anesth. Vol.3. No. 3, June 2016
 Pk Opioids Comparison

Predicted concentration of oxycodone in Predicted concentration of fentanyl in the

the plasma over time after IV administration plasma over time after administration of
of a bolus of 0.1 mg/kg followed by demand an IV bolus of 2 μg/kg followed by demand
boluses of 1 mg every 15 minutes and boluses of 15 μg every 15 minutes and
background infusion of 1 mg/h background infusion of 15 μg/h.
Choi B.M., Korean Journal Anesth. Vol.3. No. 3, June 2016
Oxycodone postoperative
 Using Oxycodone for
postoperative analgesia
 24 patients undergoing surgical procedures
 FESS , Septorhinoplasti, Timpanomastoidektomi
 Mastoidektomi, Total tiroidektomi, Parotidektomi
 Hernioraphy, SSTP, Laparotomi and Laparoskopi CBD
 Eksternal Fiksasi Tibia, ORIF Femur
 Dekompresi dan stabilisasi posterior
 0.1 – 0,4 mg/kgBW about 20-30 min before the end of
surgery with NSAIDs then continuous infusion
Oxycodone 0.01 mg/kgBW/hrs for 24 hrs then 10 mg
CR Oxycodone for 2 days
Acute Pain Services, RS Wahidin, Makassar,
Sept-oct 2017, unpublished
The observation result

 NRS on rest and dynamic : 1-3

 Ramsay score : mostly 2
 Nausea : 1/24 patients
 Total doses: 17 – 42 mg in 24 hrs
 ( difference in loading dose )
 No opioid rescue doses in 24 hrs
 Patient satisfaction : mostly very satisfaction

Acute Pain Services, RS Wahidin, Makassar,

Sept-Oct 2017, unpublished
Oxycodone for postoperative analgesia,
Indonesia

5 centers in Indonesia:

1. RSUD Soetomo – Surabaya : 15

patients
2. RS. Moh. Hoesin – Palembang :9
patients
3. RS. Wahidin Sudirohusodo – Makassar : 10
patients
4. RS. Dharmais – Jakarta :5
patients
5. RS. Siloam – Bali :1
Oxycodone for postoperative analgesia,
Indonesia
 Multicentre, 5 hospital
 (RSUD Soetomo – Surabaya, RS. Moh. Hoesin –
Palembang, RS. Wahidin Sudirohusodo – Makassar,
RS. Dharmais – Jakarta, RS. Siloam – Bali
 40 patient undergoing various surgical
techniques
 Loading IV Bolus of Oxycodone 0.07-0.18 mg/kgBW
about 10-30 min before the end of surgery then
continuous infusion Oxycodone 0.008-0.019
mg/kgBW/hr for 24 hrs after surgery in
combination with NSAID/Paracetamol
Patient variables
Parameter
Sex
Male (n) 15
Female (n) 25
Mean age (years) 42.95
Mean bodyweight (kg) 68
Mean BMI (kg/m2) 25.1
ASA
I (n) 14
II (n) 24
III (n) 1
Mean duration of surgery (hours) 2.15
 Haemodinamic stability

Perubahan MAP Perubahan Heart Rate

130.00 130.00

120.00 120.00

110.00 110.00

100.00 100.00
93.52 92.05 93.05 90.85
90.00 90.96 91.48 91.06 89.27 87.91 90.00
86.82
80.00 80.00 80.83 79.60 79.17 79.51 78.94
77.20 76.71 77.17 79.37 78.29
70.00 70.00

60.00 60.00
Observation Result

 NRS on rest and dynamic : 0-2

 Ramsay Score <2
 Nausea and vomiting : 0/40
 Total doses: 10.2 – 33.48 mg in 24 hours,
 “difference in loading dose and cont infusion”
 1/40 need opioid rescue doses in 24 hours
 Low loading dose ( 2 mg oxycodone )
 Patient satisfaction: ~ 100% patient very
satisfy with the pain management
WFSA ANALGESIA LADDER and ERAS

Opiate
And
NSAID
and
Paracetamol
Low dose
opioid

NSAID
and
Paracetamol
Pain
Paracetamol
decreases as
time passes

ERAS : ENHANCED RECOVERY AFTER ANALGESIA :

EARLY ANALGESIA
EARLY AMBULATION
EARLY ALIMENTATION
 ORAL OXYCODONE (IR and CR)
( for Postoperative Analgesia )
 26 clinical trials, with 13 RCT
 Oral oxycodone showed superior postoperative analgesic
efficacy compared with placebo in patients undergoing
laparoscopic cholecystectomy, abdominal or pelvic surgery,
bunionectomy, breast surgery, and spine surgery.
 Oral oxycodone provided better or comparable pain relief
When compared with intravenous opioids, following knee
arthroplasty, spine surgery, caesarean section, laparoscopic
colorectal surgery, and cardiac surgery.
 Conclusion : Oral oxycodone appears to offer safe and
effective postoperative analgesia, and is a well-accepted and
reasonable alternative to standard intravenous opioid
analgesics.

Cheung C.W. et al. Oral Oxycodone for Acute Postoperative Pain:

A Review of Clinical Trials. Pain Physician 2017; 20:SE33-SE52
CONCLUSION

 OXYCODONE IS AN OLD “NEW” DRUG

 GOOD ANALGESIC POTENCY AND BETTER TOLERABILITY
BASED ON THE EVIDENCE
 SAVE AND EFFECTIVE AS POSTOPERATIVE ANALGESIA
ACHIEVE WITH GOOD CLINICAL APPLICATION BASED ON
PHARMACOKINETIC PROFILE