OXYCODONE IN PAIN

MANAGEMENT
Achieving an effective and tolerable approach to the treatment
of severe cancer pain and post operative pain

OXYNEO/SLID/56/0917
 Indonesia Approved Product Information

PRODUCT INFORMATION
COMPOSITION: OXYNEO® film-coated tablets contains 10; 15; 20 mg of Oxycodone HCl with controlled released system. INDICATIONS AND USAGE: for
the treatment of severe pain in patients with cancer and post-operative pain. DOSAGE AND ADMINISTRATION: Important Dosage and Administration
Instructions : OXYNEO should be prescribed only by healthcare professionals who are knowledgeable in the use of potent opioids for the management
of chronic pain. Initial Dosage in Adults who are not Opioid-Tolerant: The starting dosage for patients who are not opioid tolerant is OXYNEO 10 mg
orally every 12 hours. Conversion from Opioids to OXYNEO in Adults Conversion from Other Oral Oxycodone Formulations to OXYNEO, administer one
half of the patient's total daily oral oxycodone dose as OXYNEO every 12 hours. Conversion from Other Opioids to OXYNEO There are no established
conversion ratios for conversion from other opioids to OXYNEO defined by clinical trials. Discontinue all other around-the-clock opioid drugs when
OXYNEO therapy is initiated and initiate dosing using OXYNEO 10 mg orally every 12 hours. Conversion from Methadone to OXYNEO Close monitoring is
of particular importance when converting from methadone to other opioid agonists. Methadone has a long half-life and can accumulate in the plasma.
Conversion from Transdermal Fentanyl to OXYNEO, ensure that the patch has been removed for at least 18 hours prior to starting OXYNEO. Start with a
conservative conversion: substitute 10 mg of OXYNEO every 12 hours for each 25 mcg per hour fentanyl transdermal patch. Dosage Modifications with
Concomitant Use of Central Nervous System Depressants Start with 1/3 to 1/2 the recommended starting dosage of OXYNEO and monitor patients for
signs of respiratory depression, sedation, and hypotension Dosage Modifications in Geriatric Patients who are Debilitated and not Opioid-Tolerant
Start dosing patients at 1/3 to 1/2 the recommended starting dosage and titrate the dosage cautiously. Dosage Modifications in Patients with Hepatic
Impairment Start dosing patients at 1/3 to 1/2 the recommended starting dosage followed by careful dosage titration. Discontinuation of OXYNEO,
gradually titrate the dosage downward to prevent signs and symptoms of withdrawal in the physically dependent patient. CONTRAINDICATIONS :
Significant respiratory depression, acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment, known or
suspected paralytic ileus and gastrointestinal obstruction, hypersensitivity (e.g., anaphylaxis) to oxycodone. WARNINGS AND PRECAUTIONS : Addiction,
Abuse, and Misuse; Life-Threatening Respiratory Depression; Neonatal Opioid Withdrawal Syndrome; Interactions with Central Nervous System
Depressants :hypotension and profound sedation, coma, or respiratory depression; Use in Elderly, Cachectic, and Debilitated Patients : Life-threatening
respiratory depression; Use in Patients with Chronic Pulmonary Disease: monitor patients with significant chronic obstructive pulmonary disease or cor
pulmonale, and patients having a substantially decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression for
respiratory depression. Please see full product information for further information on warning and precautions. ADVERSE REACTIONS: Addiction,
Abuse, and Misuse; Life-Threatening Respiratory Depression; Neonatal Opioid Withdrawal Syndrome; Interactions with Other CNS Depressants;
Hypotensive Effects; Gastrointestinal Effects; Seizures. STORAGE AND HANDLING: Store below 30°C; Dispense in tight, light-resistant container.
SUPPLY: OXYNEO 10 mg: DNI1643400114A1; 15 mg: DNI1643400114B1and 20 mg: DNI1643400114C1) are registered by PT. Kimia Farma (Persero)
Tbk. HARUS DENGAN RESEP DOKTER. Please see full product information before prescribe.
Presentation outline

Challenges in chronic pain management

Current recommendations in cancer pain management

Introducing oxycodone

Pharmacology and pharmacokinetics of Oxycodone

Clinical efficacy of oxycodone PR tablets in pain management

Tolerability and safety

Administration information

Summary
CHALLENGES IN
CHRONIC PAIN
MANAGEMENT
Chronic pain is a global health problem

Many patients suffer needlessly from poorly controlled chronic pain.

50%
15-25%

Globally, an estimated 15-25% of adults1-3

suffer from moderate-to-severe chronic pain
at any given time.
50% of patients older than 65 experience In low- and middle-income countries, 1 in 3
moderate-to-severe pain.2 adults suffer from chronic pain.4

1. International Association for the Study of Pain; European Federation of IASP Chapters. Unrelieved pain is a major global healthcare problem.
www.iasp-pain.org/AM/Template.cfm?Section=Home&Template=/CM/ContentDisplay.cfm&ContentID=2908. 2. Brennan F, et al. Pain
management: a fundamental human right. Anesth Anal 2007;105:205–221. 3. Goldberg DS, McGee SJ. Pain as a global public health priority.
BMC Public Health 2011;11:770. 4. Jackson T, et al. Prevalence of chronic pain in low-income and middle-income countries: a systematic review
and meta-analysis. Lancet 2015 Apr 27;385(Suppl 2):S10.
Chronic pain is a global health problem

In Europe, ~1 in 5 adults suffer from

moderate-to-severe chronic pain.1

Pain is often inadequately managed, with Patients with chronic pain are often
40% of patients being unsatisfied with the forced to live with pain for many years.1
effect of their treatment.1

1. Breivik H, et al. Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment Eur J Pain 2006;10:287-333.
Chronic pain interferes with patients' daily lives

Chronic pain is a major cause of disability and affects patients’ lives in many different ways.1

Chronic pain impacts on: 1-3

patients’ ability productivity and lost enjoying social and

to work working days family relationships

Chronic pain is also associated with substantial cost, due to days of lost productivity.
In Europe, absenteeism from work costs an estimated €34 billion per year4
1. Breivik H, et al. Survey of chronic pain in Europe: Prevalence, impact on daily life, and treatment. Eur J Pain 2006;10:287-333. 2. Breivik H, et al. Cancer-
related pain: A pan-European survey of prevalence, treatment, and patient attitudes. Ann Oncol 2009;20(8):1420-1433. 3. ACHEON Working Group, Kim
YC, et al. Current practices in cancer pain management in Asia: A survey of patients and physicians across 10 countries. Cancer Med 2015;4:1196-1204. 4.
The White Paper on Opioids and Pain. Opioids and Pain European Network of (OPEN) Minds, June 2005. Available at: www.pae-eu.eu/wp-
content/uploads/2013/12/Opioids-and-pain-a-Pan-European-Challenge.pdf. Accessed February 2017.
Cancer pain is poorly recognised and undertreated

More than 50% of cancer patients suffer Up to 80% of advanced stage cancer patients
ongoing pain.1 suffer uncontrolled pain.2

1. van den Beuken-van Everdingen MH, et al. Prevalence of pain in patients with cancer: A systematic review of the past 40 years. Ann Oncol
2007;18:1437–1449. 2. ACHEON Working Group, Kim YC, et al. Current practices in cancer pain management in Asia: A survey of patients and
physicians across 10 countries. Cancer Med 2015;4:1196-1204.
 Pain is widespread

Pain is under-treated

Treatment is often
sub-optimal

Breakthrough pain
is under-treated

1. European Pain in Cancer Survey, European Association of Palliative Care. Half of European cancer patients have moderate-to-severe pain: One in
five patients does not receive treatment. J Pain Palliative Care Pharmacother2007;21 :51-53.
Access to opioids is inadequate

Opioid-based analgesics are key components for treating moderate-to-severe pain. 1

In 2010, 79% of the world’s population WHO estimates that 5 billion people
had low or non-existent access to have no or insufficient access to treatment
opioid analgesics for pain relief.2 for moderate-to-severe pain.3
1. Seya MJ, et al. A first comparison between the consumption of and the need for opioid analgesics at country, regional, and global levels. J Pain
Palliat Care Pharmacother 2011;25:6-18. 2. Duthey B, Scholten W. Adequacy of opioid analgesic consumption at country, global, and regional levels
in 2010, its relationship with development level, and changes compared with 2006. J Pain Sympt Manag 2014;47:283-297. 3. International Association
for the Study of Pain. Declaration of Montreal. Seattle, WA: 2010; http://www.iasp-pain.org/DeclarationofMontreal?navItemNumber=582. Accessed
February 2017.
Access to opioids is inadequate

The barriers to adequate use of opioids come from

patient and doctors’ fears of abuse and dependence.1

Opioid importation and consumption are often strictly

regulated at the individual country level, which imposes
an additional barrier to access.2

1. Berterame S, et al. Use of and barriers to access to opioid analgesics: a worldwide, regional, and national study. Lancet 2016;387:1644–1656.
2. Hastie BA, et al. An examination of global and regional opioid consumption trends 1980-2011. J Pain Palliat Care Pharmacother 2014;28:259-275.
Access to opioids is inadequate

Global opioid use has doubled between 2001-03 and 2011-13, but use of opioid-
based analgesics remains low in many non-western regions: 1,2

• Africa

• Asia

• Central America

• Caribbean

• Eastern Europe

• South-eastern Europe

1. Berterame S, et al. Use of and barriers to access to opioid analgesics: a worldwide, regional, and national study. Lancet 2016;387:1644–1656.
2. Duthey B, Scholten W. Adequacy of opioid analgesic consumption at country, global, and regional levels in 2010, its relationship with development
level, and changes compared with 2006. J Pain Symptom Manage 2014;47:283-297.
CURRENT RECOMMENDATIONS
IN CANCER PAIN MANAGEMENT
 Opioidsfor
mild pain

1. World Health Organization (WHO). Cancer pain relief: With a guide to opioid availab ility. 2nd ed. Geneva: WHO; 1996.
The WHO 3-step ladder

The WHO 3-step pain ladder aims to assist clinicians in the effective management
of cancer pain. 1

• Non-opioids for mild pain (Step 1)

• Weak opioids for mild-to-moderate

pain (Step 2)

• Strong opioids for moderate-to-

severe pain (Step 3)

• Adjuvant analgesics
(e.g. corticosteroids and
antidepressants) can be used at
any of the 3 steps

1. World Health Organization (WHO). Cancer pain relief: With a guide to opioid availab ility. 2nd ed. Geneva: WHO; 1996.
Maltoni M, et at. A validation study of the WHO analgesic ladder: A two-step vs three-step strategy. Support Care Cancer 2005;13:888-894.
 A 2-step analgesic approach

Patients receiving Step 3 opioids early had Fewer patients receiving Step 3
superior pain relief – i.e. fewer days with opioids early were dissatisfied
pain intensity ≥5 out of 10 with therapy

Conventional treatment: treated according to WHO 3-step ladder

Innovative treatment: treated according to a 2-step approach (direct move to Step 3 after Step 1)

Maltoni M, et al. A validation study of the WHO analgesic ladder: A two-step vs three-step strategy. Support Care Cancer 2005;13:888-894.
European Association for Palliative Care

In 2012, the European Association for Palliative Care (EAPC) published a review
updating their 2001 guidelines on the use of opioid analgesics in the treatment
of cancer pain.1

• Patients with mild-to-moderate cancer pain not adequately controlled by

paracetamol or a nonsteroidal anti-inflammatory drug (NSAID) may benefit from:
– a Step 2 opioid (e.g. codeine or tramadol) given orally; or
– low doses of a Step 3 opioid (e.g. morphine or oxycodone) instead of
codeine or tramadol

• Oral IR and PR formulations of morphine, oxycodone and hydromorphone can be

used for dose titration. The titration schedules for both types of formulation
should be supplemented with oral IR opioids given as needed.

• Oxycodone is also considered one of the suitable choices of Step 3 opioids for
treatment of moderate-to-severe cancer pain.

1. Caraceni A, et al.; European Palliative Care Research Collaborative (EPCRC); European Association for Palliative Care (EAPC). Use of opioid
analgesics in the treatment of cancer pain: Evidence-based recommendations from the EAPC. Lancet Oncol 2012;13:e58-e68.
National Comprehensive Cancer Network (NCCN)

Recommendations 1

• Short-acting opioids for opioid-naive adult patients experiencing moderate-to-

severe pain.

• Slower titration of short-acting opioids to achieve adequate analgesia for

moderate pain.

• A more rapid titration of short-acting opioids when pain is severe.

• For chronic persistent pain that responds to stable doses of short-acting

opioids, conversion from a short- to a long-acting opioid should be considered.

• Treatment of opioid-related AEs is an essential aspect of successful pain

management. Such side effects are common and should be managed
appropriately.

1. National Comprehensive Cancer Network® Clinical Practice Guidelines in Oncology™. Adult Cancer Pain. Version 2.2014.
Current prescribing patterns make it difficult to
balance analgesia and side effects

Morphine is recommended as the opioid of choice for the treatment of moderate-

to-severe cancer pain 1 because it is readily available, is familiar to clinicians, has
established effectiveness, is simple to administer and is inexpensive.2

• However, the clinical response to morphine is

highly variable,2 with unsuccessful outcomes
reported in 10 to 30% of patients treated with
oral morphine.3

• Outcomes include excessive adverse effects,

inadequate analgesia, or a combination of both
these outcomes.3

1. World Health Organization. Cancer pain relief with a guide to opioid availability. 2nd ed. Geneva: The Organization; 1996. 2. Riley J, et al. No pain
relief from morphine? Individual variation in sensitivity to morphine and the need to switch to an alternative opioid in cancer patients. Support Care
Cancer 2006;14:56-64. 3. Cherny N, et al. Strategies to manage the adverse effects of oral morphine: an evidence-based report. J Clin Oncol
2001;19:2542–54..
Balancing analgesia and side effects

Current prescribing patterns make it difficult to balance analgesia and side effects.

Systemic and regulatory barriers are impeding chronic pain management

• 48.8% of doctors surveyed report a lack of pain

management or palliative care services1

• 48.0% report excessive regulation of opioid drugs1

1. ACHEON Working Group, Kim YC, et al. Current practices in cancer pain management in Asia: A survey of patients and physicians across 10
countries. Cancer Med 2015;4:1196-1204.
INTRODUCING
OXYCODONE CR TABLETS
 Chemical structure of oxycodone

Oxycodone is a semi-synthetic opioid derived from the opium alkaloid, thebaine. It is

structurally related to morphine and shares certain physico-chemical characteristics
with other opioids.1

Salzman RT, et al. Can a controlled-release oral dose form of oxycodone be used as readily as an immediate-release form for the purpose of titrating to stable
pain control? J Pain Symptom Manage 1999;18:271-279.
Oxycodone hydrochloride

• Oxycodone has been used clinically for 100 years.1

• Oxycodone effectively relieves cancer pain and post operative pain,2-4 and has
been widely acknowledged as an invaluable alternative to morphine.5,6

• Oxycodone in Indonesia are available as:7,8

– Controlled Release tablets (10 mg, 15 mg, 20 mg)

– Solution for Injection (10mg/ml)

* Capsules are not available in all countries. Korea has IR tablet & Japan has powder formulation. Abuse deterrent formulation not
available in all countries.

1.Kalso E and Vainio A. Morphine and oxycodone hydrochloride in the management of cancer pain. Clin Pharmacol Ther 1990;47:639-646.
2.Parris WC, et al. The use of controlled-release oxycodone for the treatment of chronic cancer pain: A randomized, double blind study. J Pain Symptom
Manage 1998;16:205-211. 3. Citron ML, et al. Long-term administration of controlled-release oxycodone tablets for the treatment of cancer pain. Cancer
Invest 1998;16:562-571. 4. Roth SH et al. Around-the-clock, controlled-release oxycodone therapy for osteoarthritis-related pain: placebo- controlled
trial and long-term evaluation. Arch Intern Med 2000;160:853-860. 5. Kaplan R, et al. Comparison of controlled-release and immediate- release
oxycodone tablets in patients with cancer pain. J Clin Oncol 1998;16:3230-3237. 6. Heiskanen TE, et al. Morphine or oxycodone in cancer pain. Acta
Oncol 2000;39:941-947. 7. Oxyneo Approved Indonesia Product Information. 8 Oxynorm Indonesia Approved Product Information.
Advantages of oxycodone CR tablets

• Feature a controlled – release (CR) formulation that combines prompt onset of

action with a prolonged duration of effect.1-3

• Have a short elimination half-life, so steady-state plasma levels of oxycodone are

reached after approximately 24 hours,3 allowing titration as well as maintenance
therapy.4

1. Lugo RA, Kern SE. The pharmacokinetics of oxycodone. Pain Palliat Care Pharmacother 2004;18:17-30. 2. OxyNorm ® Summary of Product
Characteristics; 14 August 2015. Napp Pharmaceuticals Ltd, Cambridge, United Kingdom. Available at:
http://www.medicines.ie/document.aspx?documentId=4290. Accessed October 2016. 3. Reder RF, et al. Steady-state bioavailability of controlled-
release oxycodone in normal subjects. Clin Ther 1996;18:95-105. 4. Salzman RT, et al. Can a controlled-release oral dose form of oxycodone be used
as readily as an immediate-release form for the purpose of titrating to stable pain control? J Pain Symptom Manage 1999;18:271-279.
Advantages of oxycodone CR tablets

Have a rapid onset of analgesic action,

Provide a significant 5-point reduction in
within 1 hour in 92% of patients,1
pain scores within the first week of use.1
significantly faster than IR morphine.2

1. Pan H, et al. Efficacy and tolerability of oxycodone hydrochloride controlled-release tablets in moderate to severe cancer pain. Clin Drug Invest
2007;27:259-267. 2. Yong L, et al. A meta-analysis comparing the efficacy and safety of oxycodone hydrochloride sustained-release tablets and
morphine immediate-release tablets in titration therapy for moderate to severe cancer pain. Chin Clin Oncol 2016;21:585-592. 3. Farrar JT, et al.
Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain 2001;94:149-158.
Oxycodone CR tablets:
A genuine therapeutic advance in pain
management

• The 12-hour sustained-release of oxycodone CR tablets provides continuous, round-

the-clock pain relief,1 with no increase in the use of rescue medication.2

• Less frequent dosing may enhance patient adherence and consistency of use.3

• Oxycodone CR tablets have a tolerable side-effect profile4 that diminishes over time
for many patients,2,4 and fewer side effects than morphine, including constipation and
nausea/vomiting.5

1. Koizumi W, et al. Efficacy and tolerability of cancer pain management with controlled release oxycodone tablets in opioid-naive cancer pain
patients, starting with 5 mg tablets. Jpn J Clin Oncol 2004;34:608-614. 2. Parris WC, Johnson BW Jr, Croghan MK, et al. The use of controlled-release
oxycodone for the treatment of chronic cancer pain: A randomized, double blind study. J Pain Symptom Manage 1998;16:205-211. 3. Graziottin A, et
al. Opioids: How to improve compliance and adherence. Pain Pract 2011;11:574-581. 4. Citron ML, et al. Long-term administration of controlled-
release oxycodone tablets for the treatment of cancer pain. Cancer Invest 1998;16:562-571 5. Yong L, et al. A meta-analysis comparing the efficacy
and safety of oxycodone hydrochloride sustained-release tablets and morphine immediate-release tablets in titration therapy for moderate to severe
cancer pain. Chin Clin Oncol 2016;21:585-592.
Oxycodone CR tablets:
A genuine therapeutic advance in pain
management

• Oxycodone CR tablets significantly reduce pain in patients with cancer pain1,2

and neuropathic pain,3,4 and significantly reduce pain and improve physical
function in patients with somatic pain.5,6
• Oxycodone CR tablets have also been shown to be effective during longer-term
(>3 months) use in cancer patients7 and patients with non-cancer pain.6,8,9

1. Pan H, et al. Efficacy and tolerability of oxycodone hydrochloride controlled-release tablets in moderate to severe cancer pain. Clin Drug Investig
2007;27:259-267. 2. Narabayashi M, et al; Advisory Committee for Oxycodone Study. Opioid rotation from oral morphine to oral oxycodone in cancer
patients with intolerable adverse effects: An open-label trial. Jpn J Clin Oncol 2008;38:296-304. 3. Watson CP, Babul N. Efficacy of oxycodone in
neuropathic pain. A randomized trial in postherpetic neuralgia. Neurology 1998;50:1837-1841. 4. Yao P, et al. Sustained-release oxycodone tablets for
moderate to severe painful diabetic peripheral neuropathy: A multicenter, open-labeled, postmarketing clinical observation. Pain Med 2012;13:107-
114. 5.Cheville A, et al. A randomized trial of controlled-release oxycodone during inpatient rehabilitation following unilateral total knee arthroplasty. J
Bone Joint Surg Am 2001;83-A:572-576. 6. Markenson JA, et al. Treatment of persistent pain associated with osteoarthritis with controlled-release
oxycodone tablets in a randomized controlled clinical trial. Clin J Pain 2005;21:524-535. 7.Citron ML, et al. Long-term administration of controlled-
release oxycodone tablets for the treatment of cancer pain. Cancer Invest 1998;16:562-571. 8. Roth SH, et al. Around-the-clock, controlled-release
oxycodone therapy for osteoarthritis-related pain: placebo-controlled trial and long-term evaluation. Arch Intern Med 2000;160:853-860. 9. Richards P,
et al. Controlled-release oxycodone relieves moderate to severe pain in a 3-month study of persistent moderate to severe back pain. Pain Med
2002;3:176. [Abstract]
 Reformulated oxycodone CR tablets

• A new formulation of oxycodone CR tablets was introduced in 2010, featuring

RESISTECTM technology, an extended-release formulation that confers resistance to
crushing, and high viscosity in aqueous solutions.1

• The abuse-deterrent formulation (ADF) of reformulated oxycodone CR tablets

potentially reduces the risk of intentional misuse of the active ingredient, oxycodone.2-4

• Reformulated oxycodone CR tablets in Indonesia are available in 10 mg, 15 mg,

20 mg.

• The reformulated oxycodone CR tablets are therapeutically equivalent to the original

oxycodone CR tablets6,7

1. Data on file, Mundipharma. 2. Coplan PM, et al. Changes in oxycodone and heroin exposures in the National Poison Data System after introduction of
extended-release oxycodone with abuse-deterrent characteristics. Pharmacoepidemiol Drug Saf 2013;22:1274-1282. 3. Cassidy TA, et al. Changes in
prevalence of prescription opioid abuse after introduction of an abuse-deterrent opioid formulation. Pain Med 2014;15:440-451. 4. Buer LM, et al. Does the
new formulation of OxyContin® deter misuse? A qualitative analysis. Subst Use Misuse 2014;49:770-774. 5. OxyContin ® US Prescribing Information; April
2014. Purdue Pharma, LP, Stamford, CT, USA. Reference ID: 3490236. 6. US Food and Drug Administration: Advisory Committee Briefing Materials For
Public Release: NDA 22-272 (reformulated OxyContin® tablets) Purdue Pharma L.P 2009. 7. US Food and Drug Administration. Therapeutic equivalence-

related terms. Available at: www.fda.gov/ohrms/dockets/ac/05/briefing/2005-4137B1_07_Nomenclature.pdf. Accessed February 2017.

Oxycodone

PHARMACOLOGY AND
PHARMACOKINETICS
Characteristics of oxycodone hydrochloride

NP, neuropathic pain; PK, pharmacokinetic.

1. Riley J et al. Oxycodone: A review of its use in the management of pain. Curr Med Res Opin 2008;24:175-192; 2. Bennett MI. Opioids. In: Bennett
MI (ed). Neuropathic Pain. Oxford: Oxford University Press; 2006:109. 3. Levy MH, et al. Advancement of opioid analgesia with controlled-release
oxycodone. Eur J Pain 2001;5(Suppl. A):113-116; 4. OxyContin® US Prescribing Information; April 2014. Purdue Pharma, LP, Stamford, CT, USA.
Reference ID: 3490236. 5. OxyNorm ® Summary of Product Characteristics; 14 August 2015. Napp Pharmaceuticals Ltd, Cambridge, United Kingdom.
Available at: http://www.medicines.ie/document.aspx?documentId=4290. Accessed October 2016.6. Kaiko RF, et al. Pharmacokinetic-
pharmacodynamic relationships of controlled-release oxycodone. Clin Pharmacol Ther 1996;59:52-61. 7. Curtis GB, et al. Relative potency of
controlled-release oxycodone and controlled-releases morphine in a postoperative pain model. Eur J Clin Pharmacol 1999;55:425-429.
Pharmacokinetics

Oral bioavailability

• Oxycodone has a high oral bioavailability compared to other strong opioids, including
morphine (60 – 87% for oxycodone1 vs. 15 – 69% for morphine2-4), to give
dependable pain relief.

• Pharmacokinetic studies have shown that the absorption of oxycodone from

oxycodone PR tablets is consistent5 and dose proportional,6 allowing for more
predictable dose titration compared to morphine CR tablets.5

1. OxyContin ® US Prescribing Information; April 2014. Purdue Pharma, LP, Stamford, CT, USA. Reference ID: 3490236. 2. Gourlay GK, et al. A
comparative study of the efficacy and pharmacokinetics of oral methadone and morphine in the treatment of severe pain in patients with cancer. Pain
1986;25:297-312. 3. Säwe J, et al. Morphine kinetics in cancer patients. Clin Pharmacol Ther 1981;30:629-635. 4. Säwe J, et al. Oral morphine in
cancer patients: in vivo kinetics and in vitro hepatic glucuronidation. Br J Clin Pharmacol 1985;19:495-501. 5. Colucci RD, et al. Relative variability in
bioavailability of oral controlled-release formulations of oxycodone and morphine. Am J Ther 2001;8:231-236. 6. Benziger DP, et al. Dose
proportionality of 10, 20, and 40 mg controlled-release oxycodone hydrochloride tablets (OxyContin ®) [abstract]. Pharmacotherapy 1995;15:391.
Pharmacokinetics

Consistent pharmacokinetic profile

• Absorption of oxycodone from oxycodone CR tablets is significantly more

consistent than the absorption of morphine from morphine CR tablets.1

• Absorption of oxycodone from oxycodone CR tablets is dose proportional,

allowing for predictable dose titration.2

• Age and gender do not significantly alter the pharmacokinetics.3

1. Colucci RD, Swanton RE, Thomas GB, Kaiko RF. Relative variability in bioavailability of oral controlled-release formulations of oxycodone and
morphine. Am J Ther 2001;8:231-236.Säwe J, et al. Morphine kinetics in cancer patients. Clin Pharmacol Ther 1981;30:629-635. 2. Benziger DP, et al.
Dose proportionality of 10, 20, and 40 mg controlled-release oxycodone hydrochloride tablets (OxyContin ®) [abstract]. Pharmacotherapy 1995;15:391.
3. Kaiko RF, et al. Pharmacokinetic-pharmacodynamic relationships of controlled-release oxycodone. Clin Pharmacol Ther 1996;59:52-61.
 Pharmacokinetics

Special patient populations

A. Hepatic Impairment
A study of OXYNEO in patients with hepatic impairement demonstrated greater
plasma concentration than those seen at equivalent doses in persons with normal
hepatic function.
Therefore, in the setting of hepatic impairement, start dosing patients at 1/3 to ½
the usual starting dose followed by careful dose titration.

B. Renal Impairement
In patients with renal impairement, as evidenced by decreased creatinine clearance
(<60ml/min), the concentration of oxycodone in the plasma are approximately 50%
higher than in subjects with normal renal function.
Follow a conservative approach to dose initiation and adjust according to the clinical
situation.

Oxyneo Approved Product Information. Indonesia. 2016.

EFFICACY IN
CANCER PAIN
Moderate-to-severe cancer pain
Efficacy and tolerability of oxycodone CR tablets

Subjects:
• 216 patients (126 male; 90 female) aged 22-84 years with a cancer pain score of ≥4
(numerical rating scale)
Study design:
• Prospective, open-label, multicentre clinical trial carried out in 10 hospitals in Zhejiang
Province, China.

• Patients with a pain score of 4-6 received oral oxycodone PR tablets at an initial dosage
of 5 mg every 12 hours, while those with a score of ≥7 initially received 10 mg every 12
hours.

• Doses were then titrated on an individual basis.

Pan H, et al. Efficacy and tolerability of oxycodone hydrochloride controlled-release tablets in moderate to severe cancer pain. Clin Drug Investig
2007;27:259-267.
Moderate-to-severe cancer pain
Efficacy and tolerability of oxycodone PR tablets

Results:
• Onset of analgesic action occurred within 1 hour in 198 cases (91.7%) of patients,
and within 30 minutes in 65 cases (30.1%).1

• Pain score decreased

significantly from baseline
after 1 week (p<0.01) and
remained low for study
duration (week 4).

• Adverse events were most

frequently noted in the first
week by 25.5% of patients,
but decreased over time.
Opioid-naive cancer patients
Efficacy and tolerability of oxycodone CR tablets

Subjects:
• 22 cancer patients (19 male; 3 female) with pain but who had not taken opioid
analgesics in the previous 2 weeks

Study design:
• Open-label, dose titration study in Japan to assess the efficacy and tolerability of
oxycodone PR tablets, starting with a 5 mg tablet every 12 hours.
• Length of time and dose required to reach stable and adequate pain control were
evaluated.
• Patients scored their pain using two different pain measurements – a 4-point
categorical scale (CAT) and a Visual Analogue Scale (VAS)*

* CAT scale: 0 = no pain, 1 = slight pain, 2 = moderate pain, 3 = severe pain.

VAS: 0 mm = no pain, 100 mm = worst possible pain.
Koizumi W, et al. Efficacy and tolerability of cancer pain management with controlled release oxycodone tablets in opioid-naive cancer pain patients,
starting with 5 mg tablets. Jpn J Clin Oncol 2004;34:608-614.
Opioid-naive cancer patients
Efficacy and tolerability of oxycodone CR tablets

Results:
• 5 mg oxycodone CR tablet gave significant pain relief 1 hour after the first dose

• Subsequent pain scores remained significantly lower than the pre-

dose scores during the following 12-hour period.

Koizumi W, et al. Efficacy and tolerability of cancer pain management with controlled release oxycodone tablets in opioid-naive cancer pain patients,
starting with 5 mg tablets. Jpn J Clin Oncol 2004;34:608-614.
Cancer pain
Long-term administration of oxycodone CR tablets

Subjects:
• 87 cancer patients who had previously participated in a double-blind study for
oxycodone PR tablets.
• Patients received oxycodone CR tablets at doses necessary to control pain (dose
titration was allowed).

Study design:
• Open-label, 3-month study to assess acceptability and side effects of oxycodone
PR tablets
Cancer pain
Long-term administration of oxycodone CR tablets

• Oxycodone CR
tablets were effective
for long-term therapy
of chronic cancer
pain.

• Patients’ mean pain

intensity remained
slight-to-moderate
throughout the study.

• Acceptability of
therapy was fair to
good throughout the
study.

Citron ML, et al. Long-term administration of controlled-release oxycodone tablets for the treatment of cancer pain. Cancer Invest 1998;16:562-571.
Cancer pain
Long-term administration of oxycodone CR tablets

• 50% of patients
reported treatment-
related AEs, mostly
mild in severity and
typical of opioid
analgesics.

• Significant decrease
in opioid-related AEs
over the study
duration (57% of
patients in week 1,
26% in week 12).

Citron ML, et al. Long-term administration of controlled-release oxycodone tablets for the treatment of cancer pain. Cancer Invest 1998;16:562-571.
Cancer pain
Switching morphine non-responders to oxycodone

Subjects:
• 186 cancer patients who required morphine for pain relief
Study design:
• Prospective observational controlled study carried out at two tertiary cancer
treatment centres in the UK.
• ‘Responders’ were those patients who had been treated with morphine for at least
4 weeks with good analgesia and minimal side effects.
• ‘Non-responders’ were patients who experienced uncontrollable pain or intolerable
side effects that were unresponsive to adjuvant medication.
• ‘Non-responders’ were switched to oxycodone tablets as a first-line therapy,
followed by either fentanyl or methadone.
Cancer pain
Switching morphine non-responders to oxycodone

Results:
• 26% of patients (48/186) had a
poor response to morphine.
• 77% (37/48) of the non-responders
responded well to oxycodone
tablets.
• A further 8% (4/48) required a
second or third switch.
Cancer pain
Switching morphine non-responders to oxycodone

Results:
• 12.5% (6/48) did not respond to any
opioid used in the study, and a
further 1 was lost to follow up.
• Pain, confusion, drowsiness,
nightmares and nausea were the
most common reasons for switching.
Cancer patients with intolerable adverse effects
Opioid rotation from oral morphine to oral oxycodone

Subjects:

• 25 cancer patients with difficulty continuing morphine therapy due to inadequate

analgesia and/or intolerable side effects

Study design:

• Prospective, multicentre, open-label, dose titration trial

• Investigating the efficacy of switching from oral morphine to oral oxycodone PR.

• Patients previously receiving oral morphine were switched to twice-daily oxycodone

PR tablets at a dose equivalent to the daily dose of morphine.

• Titration was deemed successful if adequate pain control with minimal side effects
was achieved within a maximum of 10 days.

Narabayashi M, et al.; Advisory Committee for Oxycodone Study. Opioid rotation from oral morphine to oral oxycodone in cancer patients with
intolerable adverse effects: An open-label trial. Jpn J Clin Oncol 2008;38:296-304.
Cancer patients with intolerable adverse effects
Opioid rotation from oral morphine to oral oxycodone

Switching to oral oxycodone was an effective opioid rotation strategy in Japanese

cancer patients who had difficulty in continuing oral morphine because of
inadequate analgesia and/or the occurrence of intolerable side effects.

• After switching to oxycodone PR tablets, 84% (21/25) patients achieved adequate

pain control by study end.

• Average time to pain control was 2.3 days.

Narabayashi M, et al.; Advisory Committee for Oxycodone Study. Opioid rotation from oral morphine to oral oxycodone in cancer patients with
intolerable adverse effects: An open-label trial. Jpn J Clin Oncol 2008;38:296-304.
Cancer patients with intolerable adverse effects
Opioid rotation from oral morphine to oral oxycodone

Switching to oral oxycodone was an effective opioid rotation strategy in Japanese

cancer patients who had difficulty in continuing oral morphine because of
inadequate analgesia and/or the occurrence of intolerable side effects.

• Acceptability of treatment
improved after switching to
oxycodone PR tablets, from poor
at baseline to fair at study end.
• By the end of the study, all
patients but one indicated that
their previously intolerable
morphine-induced side effects
were tolerable during oxycodone
PR tablet therapy.

Narabayashi M, et al.; Advisory Committee for Oxycodone Study. Opioid rotation from oral morphine to oral oxycodone in cancer patients with
intolerable adverse effects: An open-label trial. Jpn J Clin Oncol 2008;38:296-304.
 Moderate-to-severe cancer pain
Oxycodone CR tablets provide satisfactory efficacy

Subjects:

• 1,823* (1,121 male; 701 female) Chinese cancer patients with moderate-to-severe pain

Study design:

• Multicentre, open-label, prospective, self-controlled post-marketing surveillance trial

• Patients received oxycodone PR tablets twice daily over 8 weeks.

• Dosage was dependent on pain score – patients with a VAS score of 4-6 received 5 mg
oxycodone CR every 12 hours; patients with a VAS score of 7-10 received 10 mg
oxycodone CR tablets every 12 hours.

• Patients who had experienced inadequate pain control or intolerable side effects using
other analgesics could be switched to an equivalent dose of oxycodone CR tablets.
*Gender of 1 subject was unknown because of missing data.

#Indonesia Approved Indication is for the treatment of severe pain patient with cancer and post operative pain.
Yu SY; OxyContin ® Tablets Postmarketing Surveillance Study Group China. Postmarketing surveillance study of OxyContin ® tablets for relieving
moderate to severe cancer pain. Oncology 2008;74(suppl 1):46-51.
 Moderate-to-severe cancer pain
Oxycodone CR tablets provide satisfactory efficacy

Oxycodone CR tablets demonstrated a fast onset of cancer pain control and

good efficacy in relieving both moderate and severe cancer pain.

Pain relief within 1 hour was achieved Markedly improved: VAS pain score reduction of ≥75%;
in 86.0% of patients with moderate Response: 50-74% reduction;
pain, 90.9% of those with severe pain, Partial response: 25-49% reduction; non-response: <25% reduction.
and 89.1% of 1,822 patients overall.
#Indonesia Approved Indication is for the treatment of severe pain patient with cancer and post operative pain.
Yu SY, et al. OxyContin ® Tablets Postmarketing Surveillance Study Group China. Postmarketing surveillance study of OxyContin ® tablets for
relieving moderate to severe cancer pain. Oncology 2008;74(suppl 1):46-51.
EFFICACY IN POST
OPERATIVE PAIN
EFFICACY Controlled Release Tablet Oxycodone For Post Op Pain
after Knee or Hip Replacement

Controlled Release Tablet oxycodone every 12 hours is as effective as Standard Therapy

a. hospital stay was shorter
b. analgesic administration in the hospital was used less frequently
c. Pain intensity is lower with oxycodone compared to standard therapy

Justin de V, et. al. Efficacy and safety of controlled-release oxycodone and standard therapies for postoperative pain after knee or hip replacement. Canadian journal of surgery.
2005Aug 1;48(4):277.2005
 OXYCODONE vs Standard Therapy

Justin de V, et. al. Efficacy and safety of controlled-release oxycodone and standard therapies for postoperative pain after knee or hip replacement. Canadian journal of surgery.
2005Aug 1;48(4):277.2005
Oxycodone compared to tramadol for
post operative pain

STEFAN WIRZ, et . al. Post-operative pain therapy with controlled release oxycodone or controlled release tramadol following orthopedic
surgery: A prospective, randomized, double blind investigation . 2005. The Pain Clinic, Vol. 17, No. 4, pp. 367-376
Conclusion

Oxycodone was shown to cause less nausea and emesis than tramadol.

STEFAN WIRZ, et . al. Post-operative pain therapy with controlled release oxycodone or controlled release tramadol following orthopedic
surgery: A prospective, randomized, double blind investigation . 2005. The Pain Clinic, Vol. 17, No. 4, pp. 367-376
A PREFERRED CHOICE
TO MORPHINE?
Oxycodone CR tablets – more consistent absorption
compared to morphine

SD: Standard deviation

• Coefficients of variation were calculated based on 5 oxycodone CR studies and 7

morphine PR studies. The coefficients of variation for morphine PR tablets were
approximately 33% higher than those for oxycodone PR tablets.

• The absorption of oxycodone from oxycodone PR tablets is therefore significantly more

consistent than the absorption of morphine from morphine CR tablets.

Colucci RD, et al. Relative variability in bioavailability of oral controlled-release formulations of oxycodone and morphine. Am J Ther 2001;8:231-236.
Oxycodone CR tablets have higher bioavailability
compared to morphine CR tablets

• The main difference between the pharmacokinetics of oxycodone CR and morphine CR

tablets is in the oral bioavailability: 60-87% for oxycodone and 15-69% for morphine
(various other values for morphine bioavailability have been quoted in the literature).

Biancofiore G. Oxycodone controlled release in cancer pain. Ther Clin Risk Manage 2006;2(3):229-234.
Oxycodone PR tablets and morphine CR tablets
have comparable efficacy

• Oxycodone PR tablets have comparable efficacy to morphine CR tablets in controlling

cancer pain.1

SE, standard error.

* Categorical scale: 0 = no pain, 1 = slight, 2 = moderate, 3 = severe; † Significant decrease vs. baseline (P≤0.005); + Categorical scale: 1 = very
poor, 2 = poor, 3 = fair, 4 = good, 5 = excellent; ‡ Significant increase vs. baseline (P = 0.0001); §Significant increase vs. baseline (P = 0.0061)

1. Mucci-LoRusso P, et al. Controlled-release oxycodone compared with controlled release morphine in the treatment of cancer pain: A randomized,
double-blind, parallel-group study. Eur J Pain 1998;2:239-249.
Switching from morphine

• Proactive identification and management of patients who require opioid switching

significantly improves pain control and is reproducible across different clinical
settings.

• Switching to oxycodone significantly improves pain control in patients who experience

• uncontrolled pain or intolerable side effects with morphine.1

Riley J, Ross JR, Rutter D, et al. No pain relief from morphine? Individual variation in sensitivity to morphine and the need to switch to an alternative
opioid in cancer patients. Support Care Cancer 2006;14:56-64.
Switching therapy when receiving opioids

• The risk and impact of switching were compared in patients receiving long-acting
analgesics.

• Rates of switching at 6 months were:

– Patients without cancer: 11% (oxycodone tablets), 19% (fentanyl), 26%
(morphine)
– Compared with morphine, patients receiving oxycodone tablets or fentanyl were
significantly less likely to switch treatment

• Total healthcare charges were significantly higher for patients who switched therapy
than those who did not.

Berger A. Therapy Switching in Patients Receiving Long-Acting Opioids. Annals of Pharmacotherapy, 2004;38(3):389–395.
Need to switch to an alternative opioid in
cancer patients treated with morphine

Overall, successful pain control was achieved in 179 (96%) of the 186 patients
enrolled in the study.

Riley J, et al. No pain relief from morphine? Individual variation in sensitivity to morphine and the need to switch to an alternative opioid in cancer
patients. Support Care Cancer 2006;14:56-64.
TOLERABILITY
AND SAFETY
Adverse event profile

• The adverse event (AE) profile of oxycodone tablets is qualitatively similar to other
strong opioids.
• Most frequently reported AEs during clinical trials in cancer and chronic non-cancer
pain include constipation, nausea, vomiting, sedation, dizziness and pruritus.1-5
• Overall incidence of opioid-related common AEs decreases over time in cancer
patients treated with oxycodone PR tablets for 3 months.1

1.Citron ML, et al. Long-term administration of controlled-release oxycodone tablets for the treatment of cancer pain. Cancer Invest 1998;16:562-571.
2.Watson CP, Babul N. Efficacy of oxycodone in neuropathic pain. A randomized trial in postherpetic neuralgia. Neurology 1998;50:1837-1841. 3. Watson
CP, et al. Controlled-release oxycodone relieves neuropathic pain: a randomized controlled trial in painful diabetic neuropathy. Pain 2003;105:71-78.; 4.
McCroskery E, et al. Open-label, clinical-use study of controlled-release (CR) oxycodone in patients with post-operative pain. Proceedings of the 9th World
Congress on Pain; Aug 22-27, 1999; Vienna, Austria. Seattle: IASP Press ®; 1999:606. 5. Roth SH, et al. Around-the-clock, controlled-release oxycodone
therapy for osteoarthritis-related pain: placebo-controlled trial and long-term evaluation. Arch Intern Med 2000;160:853-860.
Adverse event profile

• The decrease in AEs

occurs with stable pain
control, despite an
increase in total daily
dose of oxycodone.1

• WHO recommends all

patients treated with
opioids receive a
laxative to counteract
opioid-induced
constipation.2

1. Citron ML, et al. Long-term administration of controlled-release oxycodone tablets for the treatment of cancer pain. Cancer Invest 1998;16:562-571.
2. World Health Organization. Cancer pain relief with a guide to opioid availability. 2nd ed. Geneva: WHO; 1996.
Adverse event profile

• Other studies have shown that oxycodone CR tablets have a good safety profile in
patients with cancer1 and non-cancer pain,2,3 over the longer term (2-3 months) and
at high doses.4

• Respiratory depression is a potentially fatal side effect with all opioid analgesics.5
– Appropriate monitoring and careful prescribing should minimise the risk
– Oxycodone CR tablets must never be crushed, chewed or broken as this could
lead to a potentially fatal overdose.5

1. Citron ML, et al. Long-term administration of controlled-release oxycodone tablets for the treatment of cancer pain. Cancer Invest 1998;16:562-571.
Markenson JA, et al. Treatment of persistent pain associated with osteoarthritis with controlled-release oxycodone tablets in a randomized controlled
clinical trial. Clin J Pain 2005;21:524-535. Richards P, et al. Controlled-release oxycodone relieves moderate to severe pain in a 3-month study of
persistent moderate to severe back pain. Pain Med 2002;3:176. [Abstract] 4.Ferrarese F, et al. Pain treatment with high-dose, controlled-release
oxycodone: An Italian perspective. Ther Clin Risk Manag 2008;4:665-67 5.OxyContin ® US Prescribing Information; April 2014. Purdue Pharma, LP,
Stamford, CT, USA. Reference ID: 3490236.
Managing adverse events

Constipation

• As with all opioids, constipation is one of

the more common side effects.

• Unlike the other side effects that resolve

over time, constipation tends to persist.

• Prescribe a stool softener or laxative.

• Advise patients to drink plenty of fluids

regularly and maintain an active lifestyle
to help reduce constipation.

American Pain Foundation. Treatment Options: A Guide for People Living with Pain. Baltimore, MD: American Pain Foundation; 2006.
Managing adverse events

Nausea and vomiting

• Nausea and vomiting are common side effects

of opioids.1

• Anti-emetic therapy can be prescribed.1,2

1. McNicol E. Opioid side effects IASP Pain Clinical Updates April 2007:Volume 15, Issue 2. 2. OxyContin® 5 mg, 10 mg, 15 mg, 20 mg, 30 mg, 40
mg, 60 mg, 80 mg and 120 mg prolonged release tablets. Summary of Product Characteristics. Updated 12 Oct 2015.
Managing adverse events

Drowsiness / Dizziness

• Another common side effect of oxycodone.1,2

• The common side effects usually resolves

after a few days.3

• As oxycodone can make you sleepy, dizzy, or

lightheaded. Advise patients to avoid:2
– Driving or operating heavy machinery
until they know how oxycodone affects
them.
– Drinking alcohol, as it may cause
oxycodone overdose.
1. McNicol E. Opioid side effects IASP Pain Clinical Updates April 2007:Volume 15, Issue 2. 2.OxyContin ® US Prescribing Information; April 2014.
Purdue Pharma, LP, Stamford, CT, USA. Reference ID: 3490236. 3. American Pain Foundation. Treatment Options: A Guide for People Living with
Pain. Baltimore, MD: American Pain Foundation; 2006.
 Possible drug interactions

CYP3A4 is the major isoenzyme involved in noroxycodone formation. Co- administration of

OXYNEO (10mg single dose) and the CYP3A4 inhibitor ketoconazole (200mg BID) increased
oxycodone AUC and Cmax by 170% and 100%,
Respectively.

CYP3A4 Inducers
A published study showed that the co-administration of rifampin, a drug metabolizing enzyme
inducer, decreased oxycodone AUC and Cmax values by 88% and 63%, respectively.

CYP2D8 Inhibitors
Oxycodone is metabolized in part to oxymorphone via CYP2D6. While this pathway may be
blocked by a variety of drugs such as certain cardiovascular drugs, such blockade has not been
shown to be clinical significance with Oxyneo.

Oxyneo Approved Product Information. Indonesia. 2016

Drug safety

Possible concerns with opioid analgesics

The risk of tolerance and physical dependence may increase with

chronic use. Addiction may also be a problem in a small number of
patients. Therefore, oxycodone PR tablets should be used with
particular care in patients with a history of alcohol and drug abuse.1,2

1. OxyContin® 5 mg, 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, 60 mg, 80 mg and 120 mg prolonged release tablets. Summary of Product Characteristics.
Updated 12 Oct 2015. 2. OxyContin® Australian Prescribing Information; November 2011. Mundipharma Pty. Ltd. Sydney, Australia.
Drug safety

Tolerance

• Tolerance may be suspected if a patient's dose begins to increase during chronic

treatment with no obvious underlying reason for the increase (e.g. disease
progression).1-3

• Patients may develop tolerance to oxycodone with chronic use. However, many
patients with chronic pain can be maintained on stable doses of opioids over a
long period of time.4

• In an 18-month study in patients with persistent stable osteoarthritis pain, no

continued increase in doses of oxycodone PR tablets was reported.5

1. Dumas EO and Pollack GM. Opioid Tolerance Development: A Pharmacokinetic/Pharmacodynamic Perspective. The AAPS Journal.
2008;10(4):537. 2. Jage J. Opioid tolerance and dependence—do they matter?. Eur J Pain 2005;9:157-162. 3. Mao J, Chen L. Opioid tolerance and
dependence. In: Smith HS (ed). Drugs for Pain. Philadelphia: Hanley and Belfus, Inc. 2003:153-156 4. Bannwarth B, Risk-benefit assessment of
opioids in chronic noncancer pain. Drug Saf 1999;21(4):283-296. 5. Roth SH, et al. Around-the-clock, controlled-release oxycodone therapy for
osteoarthritis-related pain: placebo-controlled trial and long-term evaluation. Arch Intern Med 2000;160:853-860.
Drug safety

Dependence

• Physical dependence should not be confused with addiction.1

• Physical dependence only becomes apparent after stopping therapy.

• The symptoms of withdrawal peak at around 48–72 hours after initial
discontinuation of treatment.

• Withdrawal can be avoided by a slow downward titration of the opioid dose – a

20% to 30% reduction of total daily dose every 2 to 3 days until discontinuation.

1. Mao J, Chen L. Opioid tolerance and dependence. In: Smith HS (ed). Drugs for Pain. Philadelphia: Hanley and Belfus, Inc. 2003:153-156.
Drug safety

Addiction

• Fear of addiction is one of the key causes of reluctance to use opioid analgesics1

• Addiction is a psychological and behavioral process and must not be confused with
physical dependence1

• The most important features of addiction are:1,2

– Loss of control over drug use
– Compulsive drug use
– Continued use despite drug-related harm to self and others

1. Bannwarth B, Risk-benefit assessment of opioids in chronic noncancer pain. Drug Saf 1999;21(4):283-296. 2. Mao J, et al. Opioid tolerance and
dependence, In Drugs for Pain, Smith HS, Editor. 2003, Hanley and Belfus, Inc: Philadelphia. 153-156.
Drug safety

Addiction

• Factors that may put the patient at increased risk of opioid abuse/addiction include:
– a personal/family history of substance
– prescription medication and alcohol abuse
– major psychosocial issues (e.g. psychological/psychiatric disorder)

• The use of opioids to treat predominant emotional distress should be avoided.

1. OxyContin® Australian Prescribing Information; November 2011. Mundipharma Pty. Ltd. Sydney, Australia.
ADMINISTRATION
INFORMATION
 Administering oxycodone CR tablets

• Initiate dosing regimen for each patient individually, taking into account the patient’s prior analgesic
treatment experience, and risk factor of abuse, misuse and addiction.

• Monitor patients closely for respiratory depression, especially for the first 24-72 hours of initiating
oxyneo therapy.

• Must take oxyneo tablets whole, ensure complete swallowing immediately after placing in the
mouth.

• Starting dosage for patients who are not opioid tolerant is 10mg orally every 12 hours.

• Patients who are opioid tolerant are those receiving (≥1 week) at least:
• 60mg oral morphine/day
• 25 mcg transdermal fentanyl/hour
• 30mg oral oxycodone/day
• 8mg oral hydromorphone/day
• 25mg oral oxymorphone/day
• Or an equianalgesic dose of another opioid.

BPOM Approval Oxyneo Product Information Document

Titration of oxycodone CR tablets

• Long-acting opioids are increasingly recommended to begin the initial drug titration1,2
and studies have shown that oxycodone PR is as readily titrated as an IR formulation.2

• Oxycodone PR tablets have a short elimination half-life which allows for steady-state
• plasma levels of oxycodone to be reached after approximately 24 hours.3

1. Caraceni A, et al.; European Palliative Care Research Collaborative (EPCRC); European Association for Palliative Care (EAPC). Use of opioid
analgesics in the treatment of cancer pain: Evidence-based recommendations from the EAPC. Lancet Oncol 2012;13:e58-e68. 2. Salzman RT, et al.
Can a controlled-release oral dose form of oxycodone be used as readily as an immediate-release form for the purpose of titrating to stable pain
control? J Pain Symptom Manage 1999;18:271-279. 3. OxyContin® Australian Prescribing Information; November 2011. Mundipharma Pty. Ltd.
Sydney, Australia.
Titration of oxycodone CR tablets

When titrating, oxycodone PR tablets should be administered as follows: 1,2

Adequate relief in T-I-M-E

• Titrate patients every 1 to 2 days, if necessary.
• Increase the dose of oxycodone PR tablets by 25%-50% if necessary. Do not
increase the dosing frequency.
• Manage exacerbations of pain with IR medication.
• Elevate the dose of oxycodone PR tablets if more than two doses of IR opioid
medications per day are required.

1.OxyContin® 5 mg, 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, 60 mg, 80 mg and 120 mg prolonged release tablets. Summary of Product Characteristics.
Updated 12 Oct 2015. 2. OxyContin® US Prescribing Information; April 2014. Purdue Pharma, LP, Stamford, CT, USA. Reference ID: 3490236.
Opioid switching

Opioid switching

• Patients taking an alternate opioid can be switched to oxycodone CR tablets using

the oral oxycodone equivalent of the analgesic being used. This total daily dose
should be equally divided into two 12-hourly oxycodone CR tablets doses.1

• Patients who do not respond to morphine or experience intolerable side effects can
be successfully converted to oxycodone CR tablets with fewer side effects.2

1. OxyContin® Australian Prescribing Information; November 2011. Mundipharma Pty. Ltd. Sydney, Australia. 2. Riley J, et al. No pain relief from
morphine? Individual variation in sensitivity to morphine and the need to switch to an alternative opioid in cancer patients. Support Care Cancer
2006;14:56-64.
Guide for switching:
Calculate the equianalgesic starting dose

Oral oxycodone daily dose1 x1

Oral morphine daily dose1 x 0.5

Total daily 12-hourly daily
Oral tramadol daily dose1,2 x 0.05
dose of dose of
Oral pethidine daily dose1
= OxyContin ® ÷2 OxyContin ®
x 0.1
tablets = tablets
Oral methadone daily dose1 x 1.49

Oral codeine daily dose1 x 0.15

25 µg/h fentanyl 15 mg/q 12h OxyContin ® tablets

50 µg/h fentanyl 30 mg/q 12h OxyContin ® tablets

1. OxyContin® Australian Prescribing Information; November 2011. Mundipharma Pty. Ltd. Sydney, Australia. 2. Centers for Disease Control and
Prevention, Atlanta, GA, May 2014. Available at https://www.cms.gov/Medicare/Prescription-Drug-
Coverage/PrescriptionDrugCovContra/Downloads/Opioid-Morphine-EQ-Conversion-Factors-March-2015.pdf Accessed February 2017.
SUMMARY
Treatment of cancer pain remains a challenge

• Chronic pain is a global health problem1,2 and a leading cause of disability.3

• Many patients are suffering needlessly from poorly controlled chronic cancer4,5 and
non-cancer pain.3

• Pain is poorly recognised and under-treated.3-6

• Pain affects patient’s lives in many different ways.3

1. International Association for the Study of Pain; European Federation of IASP Chapters. Unrelieved pain is a major global healthcare problem.
www.iasp-pain.org/AM/Template.cfm?Section=Home&Template=/CM/ContentDisplay.cfm&ContentID=2908. 2. Goldberg DS, McGee SJ. Pain as a
global public health priority. BMC Public Health 2011;11:770. 3. Breivik H, et al. Survey of chronic pain in Europe: Prevalence, impact on daily life, and
treatment. Eur J Pain 2006;10:287-333. 4. van den Beuken-van Everdingen MH, et al. Prevalence of pain in patients with cancer: A systematic review
of the past 40 years. Ann Oncol 2007; 18:1437–1449. 5. ACHEON Working Group, Kim YC, et al. Current practices in cancer pain management in
Asia: A survey of patients and physicians across 10 countries. Cancer Med 2015;4:1196-1204. 6. European Pain in Cancer Survey, European
Association of Palliative Care. Half of European cancer patients have moderate-to-severe pain: One in five patients does not receive treatment. J Pain
Palliative Care Pharmacother 2007;21:51-53.
Treatment of cancer pain remains a challenge

Opioid analgesics are key components for treating moderate-to-severe pain,1 but
significant barriers to opioid access exist in many countries.2,3

In 2010, 79% of the world’s population WHO estimates that 5 billion people
had less than adequate access to opioid have no or insufficient access to
analgesics for pain relief.4 treatment for moderate-to-severe pain.5

1. Seya MJ, et al. A first comparison between the consumption of and the need for opioid analgesics at country, regional, and global levels. J Pain
Palliat Care Pharmacother 2011;25:6-18. 2. Berterame S, et al. Use of and barriers to access to opioid analgesics: A worldwide, regional, and national
study. Lancet 2016; 387: 1644–1656. 3. Hastie BA, et al. An examination of global and regional opioid consumption trends 1980-2011. J Pain Palliat
Care Pharmacother. 2014 ;28:259-75. 4. Duthey B, Scholten W. Adequacy of opioid analgesic consumption at country, global, and regional levels in
2010, its relationship with development level, and changes compared with 2006. J Pain Symptom Manage 2014;47:283-297. 5. International
Association for the Study of Pain. Declaration of Montreal. Seattle, WA: 2010; http://www.iasp-pain.org/DeclarationofMontreal?navItemNumber=582.
Current prescribing patterns may not be
appropriate for all patients

• Although morphine is recommended as

the first choice of opioid to treat
moderate-to-severe pain,1 the clinical
response to morphine is highly
variable.2

• Up to 30% of patients treated with oral

morphine report unsuccessful
outcomes.3

• Switching to alternative opioids to find

a better balance between analgesia
and side effects is becoming routine in
clinical practice.2

1. World Health Organization. Cancer pain relief with a guide to opioid availability. 2nd ed. Geneva: The Organization; 1996. 2. Riley J, Ross JR,
Rutter D, et al. No pain relief from morphine? Individual variation in sensitivity to morphine and the need to switch to an alternative opioid in cancer
patients. Support Care Cancer 2006;14:56-64. 3. Mercadante S, Bruera E. Opioid switching: A systematic and critical review. Cancer Treat Rev. 2006
Jun;32(4):304-15. Epub 2006 Apr 19
Oxycodone CR tablets: Summary

• Oxycodone CR tablets are indicated for the treatment of severe pain in patient with
cancer and post operative pain.

• Oxycodone CR tablets combine a prompt onset of action with sustained duration

of effect.6
1. Parris WC, et al. The use of controlled-release oxycodone for the treatment of chronic cancer pain: A randomized, double blind study. J Pain
Symptom Manage 1998;16:205-211. 2. Citron ML, et al. Long-term administration of controlled-release oxycodone tablets for the treatment of cancer
pain. Cancer Invest 1998;16:562-571. 3. Roth SH et al. Around-the-clock, controlled-release oxycodone therapy for osteoarthritis-related pain:
placebo-controlled trial and long-term evaluation. Arch Intern Med 2000;160:853-860. 4. Kaplan R, Parris WC, Citron ML, et al. Comparison of
controlled-release and immediate-release oxycodone tablets in patients with cancer pain. J Clin Oncol 1998;16:3230-3237. 5. Heiskanen TE, et al.
Morphine or oxycodone in cancer pain. Acta Oncol 2000;39:941-947. 6. Stambaugh JE, et al. Double-blind, randomised comparison of the analgesic
and pharmacokinetic profiles of controlled- and immediate-release oral oxycodone in cancer pain patients. J Clin Pharmacol 2001 May;41(5):500-6.
Oxycodone CR tablets: Advantages

• Oxycodone has a high oral bioavailability compared to other strong opioids,

including morphine (60 – 87% for oxycodone1 vs. 15 – 69% for morphine2-4), to give
dependable pain relief.

• Exhibits fewer side effects than morphine, including constipation and

nausea/vomiting.5

• Absorption of oxycodone from oxycodone PR tablets is significantly more consistent

than the absorption of morphine from morphine PR tablets.6

1. OxyContin ® US Prescribing Information; April 2014. Purdue Pharma, LP, Stamford, CT, USA. Reference ID: 3490236. 2. Gourlay GK, et al. A
comparative study of the efficacy and pharmacokinetics of oral methadone and morphine in the treatment of severe pain in patients with cancer. Pain
1986;25:297-312. 3. Säwe J, et al. Morphine kinetics in cancer patients. Clin Pharmacol Ther 1981;30:629-635. 4. Säwe J, et al. Oral morphine in
cancer patients: in vivo kinetics and in vitro hepatic glucuronidation. Br J Clin Pharmacol 1985;19:495-501. 5. Yong L, et al. A meta-analysis
comparing the efficacy and safety of oxycodone hydrochloride sustained-release tablets and morphine immediate-release tablets in titration therapy
for moderate to severe cancer pain. Chin Clin Oncol 2016;21:585-592. 6. Colucci RD, Swanton RE, Thomas GB, Kaiko RF. Relative variability in
bioavailability of oral controlled-release formulations of oxycodone and morphine. Am J Ther 2001;8:231-236.
Oxycodone CR tablets: Efficacy

• Oxycodone CR tablets have a rapid onset of action,

within one hour in 92% of patients.1

• The 12-hour sustained-release of oxycodone CR

tablets provides continuous, round-the-clock pain
relief.2

• Predictable and reliable pharmacokinetic profile,3 with

steady-state plasma levels reached within
approximately 24 hours.4

• Oxycodone CR tablets have a tolerable side-effect

profile that diminishes over time.5

1. Pan H, et al. Efficacy and tolerability of oxycodone hydrochloride controlled-release tablets in moderate to severe cancer pain. Clin Drug Invest
2007;27:259-267. 2. Koizumi W, et al. Efficacy and tolerability of cancer pain management with controlled release oxycodone tablets in opioid-naive
cancer pain patients, starting with 5 mg tablets. Jpn J Clin Oncol 2004;34:608-614. 3. Levy MH et al. Advancement of opioid analgesia with controlled-
release oxycodone. Eur J Pain 2001;5(Suppl. A):113-116; 4. Reder RF, et al. Steady-state bioavailability of controlled-release oxycodone in normal
subjects. Clin Ther 1996;18:95-105. 5. Citron ML, et al. Long-term administration of controlled-release oxycodone tablets for the treatment of cancer
pain. Cancer Invest 1998;16:562-571
Oxycodone CR tablets: Safety

• Oxycodone CR tablets have a predictable

pharmacodynamic profile,1 with no ceiling effect to
analgesia.2

• The lack of clinically significant metabolite activity of

oxycodone1 contributes to oxycodone’s favourable
adverse event profile.

• No dose adjustment is required for elderly patients.2,3

• The range of dose strengths allows conservative

administration in patients with mild renal or hepatic
impairment.3,4

1. Levy MH, et al. Advancement of opioid analgesia with controlled-release oxycodone. Eur J Pain 2001;5(Suppl. A):113-116 2. Salzman RT, et al.
Can a controlled-release oral dose form of oxycodone be used as readily as an immediate-release form for the purpose of titrating to stable pain
control? J Pain Symptom Manage 1999;18:271-279. Oxycodone Approved Product Information. Indonesia. April 2016. 4. Kaiko R, et al. Clinical
pharmacokinetics of controlled-release
oxycodone in renal impairment [abstract]. Clin Pharmacol Ther 1996;59:130.
Reformulated oxycodone CR tablets: Safety

• The abuse-deterrent formulation (ADF*) of reformulated oxycodone CR tablets

potentially reduces the risk of intentional misuse of the active ingredient,
oxycodone.1-3

• RESISTECTM technology is an extended-release formulation with a unique

polymer and processing that confers resistance to crushing, and high viscosity in
aqueous solutions.4

• The reformulated oxycodone CR tablets* are therapeutically equivalent to the

original oxycodone PR tablets.5,6

* Abuse deterrent formulation not available in all countries

1. Coplan PM, et al. Changes in oxycodone and heroin exposures in the National Poison Data System after introduction of extended-release 2.
oxycodone with abuse-deterrent characteristics. Pharmacoepidemiol Drug Saf 2013;22:1274-1282. 3. Cassidy TA, et al. Changes in prevalence of
prescription opioid abuse after introduction of an abuse-deterrent opioid formulation. Pain Med 2014;15:440-451. 4. Buer LM, et al. Does the new
formulation of OxyContin® deter misuse? A qualitative analysis. Subst Use Misuse 2014;49:770-774. Data on file, Mundipharma 5. US Food and Drug
Administration: Advisory Committee Briefing Materials For Public Release: NDA 22-272 (reformulated OxyContin® tablets) Purdue Pharma L.P 2009 6.
US Food and Drug Administration. Therapeutic equivalence-related terms. Available at: www.fda.gov/ohrms/dockets/ac/05/briefing/2005-
4137B1_07_Nomenclature.pdf. Accessed January 2014.
Oxycodone CR tablets: Ease of titration

• Oxycodone CR tablets have a short elimination

half-life, with steady-state plasma levels of
oxycodone reached after approximately 24 hours,1
allowing for rapid titration.

• Choice of formulations and range of tablet strengths

increases flexibility and allows tailored individual
pain relief.2

• Colour coding of tablets allows easy identification.2

• Immediate-release formulation available for

breakthrough pain in cancer pain management.3

1. OxyContin® Australian Prescribing Information; November 2011. Mundipharma Pty. Ltd. Sydney, Australia. 2. OxyContin® 5 mg, 10 mg, 15 mg, 20
mg, 30 mg, 40 mg, 60 mg, 80 mg and 120 mg prolonged release tablets. Summary of Product Characteristics. Updated 12 Oct 2015. 3. OxyNorm®
Summary of Product Characteristics; 14 August 2015. Napp Pharmaceuticals Ltd, Cambridge, United Kingdom. Available at:
http://www.medicines.ie/document.aspx?documentId=4290Accessed October 2016.
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