Download oxycodone/naloxone controlled release

January 17, 2012
Formulary Drug Listing Decisions
OXYCODONE/NALOXONE CONTROLLED RELEASE
Indication (s)
Drug Profile
Products available in
Canada:
TARGIN™
(oxycodone/naloxone
controlled release)
Manufacturer:
Purdue Pharma
n There are no long-term trials (beyond
12 weeks) investigating the efficacy
The relief of moderate to severe pain in
of oxycodone/naloxone CR in chronic
adults who require continuous, aroundpain.
the-clock opioid analgesia for several
days or more. The naloxone component is n Oxycodone/naloxone CR has been
associated with improvements in
indicated for the relief of opioid-induced
constipation outcomes compared to
constipation (OIC).
OxyContin®. However, outcomes such
as patient well-being or quality of life
DAC Recommendation
have not been investigated.
The Drug Advisory Committee (DAC)
n The efficacy of oxycodone/naloxone CR
recommended that oxycodone/naloxone
has not been compared adequately to
controlled release (CR) NOT be listed on
OxyContin® plus a preventative bowel
any WSIB formulary as there are no trials
regimen.
providing evidence that it demonstrates
an advantage to comparators currently
n Oxycodone/naloxone CR is associated
listed on the WSIB formularies.
with adverse effects consistent with
opioid therapy.
The WSIB Decision
n Although naloxone may theoretically
Based on the DAC’s recommendation, the
WSIB has decided NOT to list oxycodone/
naloxone CR on any of the WSIB formularies at this time.
Formulary Status
Oxycodone/naloxone CR IS NOT listed on
any WSIB formularies at this time.
Recommendation Highlights
n Oxycodone/naloxone CR is a combi-
nation product containing the opioid
analgesic oxycodone and is currently
approved for the treatment of moderate to severe pain in adults who require
continuous, around-the-clock opioid
analgesia for several days or more.
Naloxone is an opioid antagonist that
has been added to alleviate oxycodoneinduced constipation.
lower the risk of opioid abuse, studies
pertaining to the abuse potential of
oxycodone/ naloxone CR have not been
published.
n No cost-effectiveness studies were
located.
n The DAC concluded that an indepen-
dent review of the clinical efficacy,
safety, and cost-effectiveness of oxycodone/naloxone CR did not indicate any
therapeutic or non-therapeutic advantage in the treatment of chronic noncancer pain over appropriate comparators available on WSIB formularies.
Consequently, the DAC recommended
that oxycodone/ naloxone CR NOT be
listed on any WSIB formulary.
n Oxycodone/naloxone CR appears to
provide similar (but not superior) analgesic efficacy to OxyContin®.
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DETAILED DISCUSSION
Background
Oxycodone/naloxone controlled release (CR)
is a long-acting combination opioid product
marketed as Targin™ in Canada. Oxycodone
is a mu opioid receptor agonist that provides
analgesic relief. Naloxone is an opioid receptor antagonist, added to counteract oxycodone-induced constipation. Naloxone has
limited oral systemic bioavailability; its effect
is limited to the gastrointestinal tract and,
as such, it will not induce opioid withdrawal
when taken orally. However, non-oral routes
of administration can induce withdrawal
effects.
Summary of Committee
Considerations
The DAC considered an external, independent review of the clinical efficacy, safety, and
cost-effectiveness of oxycodone/naloxone CR
in the treatment of chronic non-cancer pain
(CNCP). The review included published and
unpublished randomized controlled trials
(RCTs) that were at least single-blind.
Three RCTs comparing oxycodone/naloxone
CR to OxyContin® or placebo were included
in the review. The studies enrolled subjects
reporting moderate to severe pain secondary
to musculoskeletal (mainly lower back pain or
osteoarthritis) or neurological conditions. All
trials were of 12 weeks duration. Bowel function was the primary outcome investigated
in two trials, while occurrence of pain events
was the primary outcome in the third trial.
No significant differences between oxycodone/naloxone CR and OxyContin® were reported in any of the trials in mean daily oxycodone doses, measures of pain, or the need
for rescue medications. Inadequate reporting
of treatment estimates, lack of non-inferiority
design, and the short duration of the trials
were notable limitations in demonstrating
equivalent analgesic efficacy between oxycodone/naloxone CR and OxyContin®.
Oxycodone/naloxone CR was associated with
better bowel function compared to OxyContin® (e.g., lower constipation-related effects,
higher frequency of bowel movements, and
lower use of laxatives). The clinical relevance
of these effects with respect to patient wellbeing and quality of life were not assessed.
It is uncertain if subjects taking OxyContin®
concurrently used an adequate preventative
bowel regimen. As such, the clinical benefit of
oxycodone/naloxone CR versus Oxycontin®
and an adequate preventative bowel regimen
has not been established (guidelines generally recommend preventative bowel regimens
be prescribed with opioids).
The most commonly reported adverse effects
for oxycodone/naloxone CR across all trials
were gastrointestinal (constipation, diarrhea,
nausea, and vomiting). The abuse potential
of oxycodone/naloxone CR has not been
investigated in any published trials. Although
the naloxone component of the product may
confer a potentially lower risk of abuse and
addiction compared to other opioids, studies
demonstrating such an advantage are lacking.
No cost-effectiveness studies were identified.
The Canadian Guideline for Safe and Effective
Use of Opioids for Chronic Non-cancer Pain
recommends a stepped approach when initiating opioids in individuals who have been
thoroughly assessed and screened.
The Ontario Drug Benefit Program does not
list oxycodone/naloxone CR as a general
benefit. The drug is currently under consideration by the Common Drug Review.
Based on the available evidence, the DAC
concluded that there was no compelling
evidence demonstrating a therapeutic or
non-therapeutic advantage for oxycodone/
naloxone CR over opioid comparators (plus
a preventative bowel regimen) in the treatment of CNCP. Furthermore, several alternative drug classes and laxatives are available
on the WSIB formularies that can meet the
treatment needs of the majority of injured/ill
workers. Hence the DAC recommended that
oxycodone/naloxone CR not be listed on any
WSIB formularies.
Revised: January 29, 2013
The WSIB will consider all relevant facts and circumstances, and shall make its decision based upon the merits and
justice of a particular case.
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