Download Opioid rotation - an update on the evidence

Opiod rotation an update
Augusto Caraceni
Director Palliative care, Pain Therapy,
Rehabilitation Fondazione IRCCS Istituto
Nazionale Tumori di Milano
Definition
Rotation
or switch ? The term switch is
now preferred to indicate a change from
one opioid to another one although
rotation was a more enticing way to say
the same thing
Entia non sunt multiplicanda sine necessitate
Sources of variation in opioid analgesia
Age
Race
Pain intensity
Pain site
Pain characteristics
Plasma disposition
Kaiko et al 1988
Tolerance
Pharmacodynamics
Metabolites
Pharmacokinetics
Genetic variance
Individual response
Methadone plasma levels and analgesia in two different subjects
Inturrisi 1988
Tolerance (?)
equianalgesic dose
Tolerance can affect equianalgesic dose ratio
R = 2.6
40
30
R = 2.0
20
Morphine
Metopon
10
0
Before
The key concept
could be incomplete
cross tolerance
Mercadante 2009
After
Morphine 77 mg day for
8 days
Houde 1966
Clinical indication
Poor
opioid responsiveness is defined by
a unsatisfactory level of analgesia
despite gradual dose titration due to the
onset of unmanageable side effects
Frequency
Mercadante
2009
Mueller-Busch 2005
Riley J 2006
Walsh D 2002
Cherny 1995
%
34
12
25
15
80
n
345
412
186
275
100
Clinical indication
Uncontrolled pain with side effects 51%
Side effects with adequate pain control 29%
Uncontrolled pain despite rapid escalation 15%
Mercadante et al J Pain Sympt Manage 2009
What is the evidence ?
Quigley C 2007 Cochrane review covering the
literature 1966-2004
14 prospective studies *
15 retrospective studies
22 case reports
399 patients*
Updating the review 2004-2009
7
prospective observational trials 229
patients
1995-2004
14 reports
399 cases
2004-2009
7 reports
229 cases
Clinical practice conclusions
Most switches occurs when pain is not well
controlled and side effects are significant
Some only to avoid excessive side effects
Switching most often is done to methadone
Succes rate ranges from 40 to 80%
Indelicato RA & Portenoy RK J Clin Oncol 2002; 20: 348
Moryl N, Foley KM, Coyle N. “…pain crisis: this is much of
a crisis as a code” JAMA 2008 26 ; 299: 1457
Equipotency - Equianalgesia
“Relative potency is the ratio of doses
of two drugs required to produce a
given level of effect”
Houde et al 1966 In Lasagna L (ed) International encyclopedia
of pharmacology and therapeutics. Section 6 Clinical
Pharmacology, Pergamon Press NY, pp 59-99
Dose ratio ? The example of methadone
Review (including retrospective data) on 658 pts
Ratio from Morphine oral equivalent dose (OME)
to oral methadone varies > 4:1 ; 5:1 10:1
Methadone dose is dependent on previus OME
RATIO is dependent on OME
Individual variability is however very high
Weschules DJ Pain Medicine 2008
Expert Advice
..“Practically speaking, the equianalgesic dose ratio
controversy reflects, in part, an attempt to develop simple
cook-book guidelines for dosing opioids that do not reflect
the complicated and still poorly understood pharmacologic
aspects of drug dosing and drug metabolism.
Equianalgesic tables have been debated, debunked,
misinterpreted and misrepresented”...
Foley KM and Houde R, Methadone in cancer pain management:
individualize dose and titrate to effect J Clin Oncology 1998, 16: 3213
Conclusions for research
The
level of evidence is poor
No controlled randomized trial
Definition of patient population
Poor opiod response definition
Switch from what to what
Equianalgesic ratio
Outcome measures