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Drug Update
Tapentadol
Sujatha MB1
www.kjoonline.org
Govt. Medical College
Thrissur,Kerala, India
1
Assoc. Professor of
Pharmacology
Correspondence should
be sent to:
[email protected]
Introduction
Tapentadol is a novel centrally acting synthetic
analgesic with mu-opioid receptor agonism and
norepinephrine reuptake inhibition in a single
molecule. It is approved for the treatment of
moderate to severe pain in adults, 18 years of age
or older.
It is well known that mu-opioid receptor
agonists and norepinephrine reuptake inhibitors
have analgesic effects, although the pain conditions
in which these two drug classes are most efficacious
may be different. It appears that, overall, mu-opioid
agonists are predominantly effective against acute,
moderate to severe pain, whereas, norepinephrine
reuptake inhibitors are particularly effective against
chronic pain.This implies that a compound that
combines both mechanism of action holds the
promise of being effective against a large spectrum
of pain conditions,ranging from acute to chronic
pain.
Chemical structure
Chemically, Tapentadol is 3-3(dimethylamino)-1(ethyl-2-methylpropyl) phenol
monohydrochloride.(Figure. 1)
Mechanism of action
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It is structurally and mechanistically similar
to Tramadol .It displays a dual mode of action,
has mild opioid activity and possesses monoamine
reuptake inhibitor activity also. (Figure. 2)
Combining mu-opioid receptor agonism
with monoamine reuptake inhibition is an
approach to improve the therapeutic range of
opioids. The different complementary mechanism
of action may additively or even synergistically
enhance the analgesic efficacy and or attenuate the
side effect of mu-opioid receptor agonists by
reducing the requirement for mu-opioid receptor
activation.(Opioid sparing effect). The facilitation
of mono aminergic transmission in descending
pain inhibitory pathways in the spinal cord seems
to be an important mechanism because
compounds that block the reuptake of
norepinephrine and/or serotonin are efficacious
in the treatment of chronic painful conditions and
can enhance the analgesic effect of morphine.
This is of particular relevance because
neuropathic pain is generally considered to be
unresponsive to opiates and or difficult to treat
effectively because of mu- opioid receptor related
side effects. Attempts to circumvent this problem
initially led to the development of Tramadol.
Tramadol is an atypical, racemic opioid that
combines weak mu-opioid receptor(MOR)
activation with inhibition of norepinephrine and
serotonin reuptake. This combination of
complementary mechanisms of action results in
potent analgesic activity. Thus the broad analgesic
profile of Tapentadol and its relative resistance to
tolerance development may be due to a dual mode
of action consisting of both Mu-opioid receptor
activation and Nor epinephrine reuptake inhibition.
Kinetics
Kerala Journal of
Orthopaedics
2012;25:119-122
© Kerala Journal of
Orthopaedics
Figure. 1. Chemical structure of Tapentadalol
Kerala Journal Of Orthopaedics Volume 25 | Issue 2 | July 2012
Tapentadol is administered orally. It is
metabolised predominantly by glucuronidation.
The metabolite is devoid of any analgesic activity
and is mainly excreted in urine in the conjugated
form. The plasma half life is approximately 4 hrs
after oral administration.
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Drug Update
Sujatha et.al: Tapentadol
Figure. 2. Mechanism of action of Tapentadalol
Therapeutic use
Tapentadol immediate release tablets have been approved
by the FDA in 2008 for the relief of moderate to severe acute
pain in adults and in 2011, for chronic pain in an extended
release form.
The approval was based on data from clinical studies
involving more than 2,100 patients. This showed that
Tapentadol provided significant relief of moderate to severe
acute pain compared to a placebo and that the medicine was
generally well tolerated.
The studies were conducted in different patient groups,
including those who had a bunionectomy, a standard foot surgery
associated with predictable levels of moderate to severe pain,
and in those with pain from end-stage joint disease.
120
(Figure courtesy: Medscape.com)
A Phase 3 safety study of Tapentadol immediate-release
tablets evaluated Tapentadol in patients with low back pain or
pain from osteoarthritis of the hip or knee. It demonstrated
that Tapentadol offers pain relief and is generally well tolerated.
All trials utilised a 0-10 point scale for pain intensity (none
to worst) and 0-5 point scale for pain relief (none to complete).
Patients were assessed at time intervals and the sum of numerical
values for these pain scales were the basis of evaluating efficacy.
Secondary endpoints of total pain relief from baseline, time to
pain relief, time to first rescue medication and the need for rescue
medication were important clinically relevant endpoints.
These published phase II and phase III studies used active
control medications including Oxycodone, morphine or
NSAIDs.
Kerala Journal of Orthopaedics Volume 25 | Issue 2 | July 2012
Drug Update
Sujatha et.al: Tapentadol
Adverse effects
The most common side effects reported with Tapentadol
are nausea, vomiting, dizziness, headache & somnolence. In
clinical trials, Tapentadol has been shown to provide equianalgesic
effect with a lower incidence of side effects compared to
Oxycodone and morphine.
Precautions & contraindications
Tapentadol is contraindicated in any situation where muopioid receptors are contraindicated. ie. in significant respiratory
depression, acute or severe bronchial asthma, in patients with
paralytic ileus or in patients concurrently using or within 14 days
of using monoamine oxidase inhibitors.
every 4-6 hrs depending upon pain intensity.
Extended release tablets – 100-250 mg twice daily.
Conclusion
Tapentadol is a new analgesic drug with a dual mode of
action and is effective in the treatment of both acute and chronic
moderate to severe pain in adults. Its dual mode of action
provides analgesia at similar levels of more potent narcotic
analgesics with more tolerable side effect profile.
Patients receiving other opioid analgesics, general
anaestetics, Phenothiazines, Tranquilizers or other CNS
depressants concomitantly with Tapentadol may exhibit an
additive CNS depression. When such combined therapy is
contemplated, a dose reduction of one or both agents should
be considered.
Like other drugs with mu-opioid agonist activity,
Tapentadol should not be used in patients with head injury,
increased intracranial tension etc. Tapentadol should be used
with caution in patients with pancreatic or biliary tract disease
and moderate hepatic impairment.
Tapentadol should be prescribed with care in patients with
a history of seizure disorder or any condition that would put
the patient at risk of seizure. The development of a potentially
life threatening serotonin syndrome may occur with the
concurrent use of serotonergic drugs like Selective serotonin
reuptake inhibitors(SSRI), Serotonin-norepinephrine reuptake
inhibitors(SNRI), Triptans etc.
Because elderly patients are more likely to have decreased
renal and hepatic function, consideration should be given to
start elderly patients with the lower range of recommended doses.
Tapentadol can be abused in a manner similar to other
opioid agonists. This risk is increased with concurrent abuse of
Tapentadol with alcohol and other substances. Monitor patients
closely for signs of abuse and addiction.
Tapentadol may impair the mental or physical abilities
required for the performance of potentially hazardous tasks such
as driving a car or operating machinery.
Dosage and administration
Tapentadol immediate release tablets - 50mg- 100mg orally
Kerala Journal Of Orthopaedics Volume 25 | Issue 2 | July 2012
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Source of funding: Nil; Conflict of interest: Nil
Cite this article as:
Sujatha MB. Tapentadol.Kerala Journal of Orthopaedics 2012;25:119-122
122
Kerala Journal of Orthopaedics Volume 25 | Issue 2 | July 2012