Download cannabinoids: cesamet®, marinol®, and sativex

May 11, 2009
Formulary Drug Listing Decisions
CANNABINOIDS:
CESAMET®, MARINOL®, AND SATIVEX®
Indication (s)
Treatment of severe nausea and
vomiting associated with cancer
chemotherapy. (Marinol, Cesamet)
Treatment of AIDS-related anorexia.
(Marinol)
Adjunctive treatment of neuropathic
pain in multiple sclerosis (MS), and for
adjunctive pain treatment in patients
with advanced cancer. (Sativex)
Drug Profile
Products available in
Canada:
CESAMET® (nabilone)
Manufacturer: Valeant
Canada Ltd.
MARINOL® (dronabinol)
Manufacturer: Solvay
Pharma
SATIVEX® (delta-9-tetrahydrocannabinolcannabidiol)
Manufacturer: GW
Pharma/Bayer
DAC Recommendation
The DAC recommended that the three
synthetic cannabinoid products not
be listed on any WSIB formularies, as
there is no evidence to suggest that
they offer any advantage to comparators currently on WSIB formularies.
The WSIB Decision
Based on the DAC’s recommendations,
the WSIB has decided NOT to list
Cesamet®, Marinol®, or Sativex® on
any formulary at this time.
Formulary Status
Cesamet®, Marinol®, and Sativex®
ARE NOT listed on any WSIB formularies at this time.
Recommendation Highlights
The term cannabinoids refers to the
three synthetic cannabinoid medications currently available in Canada
– Cesamet®, Marinol®, and Sativex®.
Of these agents, only Sativex® is
approved by Health Canada for the
treatment of pain of any type (see
indications).
Only Cesamet® has been directly
compared with another pain medication in a randomized, controlled
trial. Compared to the weak opioid
dihydrocodeine, Cesamet® was less
effective and was associated with
more adverse effects in the treatment of neuropathic pain.
Studies have not demonstrated any
therapeutic or safety advantage of
using cannabinoid medications over
conventional pain medications.
The daily costs of the cannabinoid
agents is significantly greater than
that of most conventional pain
medications proven effective and
safe. No pharmacoeconomic studies
relevant to the WSIB were located.
The DAC concluded that an independent review of the clinical efficacy,
safety, and cost-effectiveness of
Cesamet®, Marinol®, and Sativex® in
the treatment of chronic non-cancer
pain (CNCP) did not demonstrate
any significant therapeutic or
non-therapeutic advantage over
appropriate comparators available in
Canada. Consequently, DAC recommended that these products NOT be
listed on any WSIB formulary.
Page 1 of 2
DETAILED DISCUSSION
Background
The term cannabinoids refers to the three
synthetic medications whose active ingredient
is derived from the cannabis plant (Cannabis
sativa). Cesamet® is chemically similar to
the active ingredient in marijuana, delta9-tetrahydrocannabinol (delta-9-THC). Sativex®
and Marinol® both contain the active ingredient
delta-9-THC. The cannabinoids complex effects
on the central nervous system are thought to be
mediated by their action at the cannabinoid 1
receptor (CB1).
The effects of delta-9-THC in humans are
diverse. They are thought to include appetite
stimulation, antiemesis, analgesia, muscle
relaxation, euphoria, reduction in intraocular
pressure, reflux, fatigue, tachycardia, anxiety,
and disorientation.
Although cannabinoid products may be
prescribed to treat pain, concerns exist in the
medical literature regarding their long-term use
and potential for serious adverse effects and
drug interactions.
a single-dose trial (i.e., a single dose of Marinol® or placebo was given to subjects on three
separate occasions and pain relief was assessed
8 hours later). Sativex® showed only clinically
modest effects in two placebo-controlled trials,
one in allodynia and one in brachial plexus
avulsion.
The DAC also considered safety issues associated with these medications. The cannabinoids
have significant neurological adverse effects,
including dizziness, somnolence, ”feeling
drunk”, vertigo, euphoria, dysphoria, disorientation, hallucination, paranoia, anxiety, amnesia,
confusion, and others. Furthermore, caution is
urged in prescribing these agents to individuals
on concomitant psychoactive medications (due
to the potential for additive effects) and those
with a current or past history of psychiatric
illness.
Summary of Committee Considerations
National and international guidelines for the
treatment of CNCP were also considered. In
general, evidence-based guidelines do not mention the use of cannabinoids. The exception is a
Canadian guideline for neuropathic pain, which
lists cannabinoids as a fourth-line treatment
option.
The DAC considered an external, independent
review of the clinical efficacy, safety, and
cost-effectiveness of Cesamet®, Marinol®, and
Sativex® in the treatment of CNCP. The review
included published and unpublished, randomized controlled trials (RCTs) that were at least
single-blind.
The Ontario Drug Benefit (ODB) Program funds
Sativex® under the Exceptional Access Program
only for individuals with multiple sclerosis who
meet their criteria. Cesamet® is listed under
antiemetic and antinauseant medications. ODB
lists Marinol® only for its approved indications
(not for pain).
Five RCTs were included in the review – one
active comparator trial and 4 placebo-controlled
trials. Cesamet® was compared with the weak
opioid dihydrocodeine (not available in Canada)
in chronic neuropathic pain and shown to
be less effective and to cause more adverse
effects. Cesamet® was also evaluated versus
placebo for fibromyalgia pain, and was shown
to reduce pain according to the Fibromyalgia
Impact Questionnaire (FIQ). There are no RCTs
evaluating Marinol® or Sativex® against active
comparators. Marinol® has only been evaluated against placebo as adjunctive therapy in
patients with chronic pain already on opioids in
Based on the published and unpublished
evidence, the DAC concluded that there was
no compelling evidence demonstrating a
therapeutic or non-therapeutic advantage for
cannabinoids in the treatment of illness/injuries
common to the WSIB population. Furthermore,
cannabinoids are associated with numerous
safety issues. Hence, the DAC recommended
that Cesamet®, Marinol®, and Sativex® 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.
Page 2 of 2