Page 94 WHO - Guidelines on the pharmacological treatment of persisting pain in children with medical illness

Cost
Immediate-release oral morphine is relatively inexpensive but may not be commercially available
in all countries. Morphine powder for extemporaneous preparation may be available, but requires A1
access to pharmacists and suitable diluents, and its compounding may be subject to legal restrictions.
The stability of such preparations needs to be investigated.
Uncertainty: none.

Feasibility
No problem of feasibility, rather affordability for prolonged-release morphine formulation. A2 A2
Uncertainty: none.

Research agenda
Research into appropriate formulations for the extemporaneous preparation of oral liquid morphine
is needed. Dissemination of available evidence on the preparation of stable extemporaneous
formulations is encouraged.
A3

A2.2.6 Opioid rotation and opioid switching
Clinical question
In children with persisting pain due to medical illnesses, what is the evidence to support opioid rotation
policies to prevent dose escalation and side-effects?
Recommendations A4
10. Switching opioids and/or route of administration in children is strongly recommended in the
presence of inadequate analgesic effect with intolerable side-effects.
11. Alternative opioids and/or dosage forms as an alternative to oral morphine should be available to
practitioners, in addition to morphine, if possible.
12. Routine rotation of opioids is not recommended.
Strong recommendations, low quality of evidence A5

Domains and considerations

Quality of evidence
No systematic reviews or randomized control trials were found in children. A Cochrane Review
exclusively looked for and found no RCTs on opioid switching or rotation in adults and children.
Identified case reports, uncontrolled and retrospective studies were examined in order to determine A6
the current level of evidence (116). The review concluded that although for patients suffering chronic
cancer pain opioid switching may be the only option for enhancing pain relief and minimizing
opioid toxicity, there is a current lack of an evidence base for this therapeutic strategy. A systematic
review published in 2006 (117), identified one retrospective study of opioid switching in 22 children
with cancer pain. This review described a positive response to switching in patients intolerant
to a particular opioid, but noted that RCTs are lacking and that the observations were based on
uncontrolled data. A7
Uncertainty: yes, in relation to the potential utility of rotation policies; no, in relation to switching of
opioid and/or route of administration in the presence of inadequate effect or intolerable side-effects.

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