Page 88 WHO - Guidelines on the pharmacological treatment of persisting pain in children with medical illness

Risks/benefits
Benefits
The potential benefit of having access to effective opioid analgesics outweighs the benefits of codeine A1
in this age group.
Risks
The risks associated with strong opioids are recognized, but are acceptable in comparison to the
uncertainty associated with codeine and tramadol.
Uncertainty: if there is new evidence for tramadol or an alternative intermediate potency opioid, then
this benefit-risk assessment can be reconsidered.
A2 A2

Values and acceptability
In favour
The panel placed high value on effective treatment of pain.
Against
The panel acknowledged continuing barriers to access to strong opioids in many settings, but a
strong recommendation in this regard could overcome this negative sentiment and promote wider
access to opioids for pain relief. A3
Uncertainty: none.

Cost
Although tramadol is now off patent in many markets and generics have been launched, the problem
of market authorization for children remains in several countries. Codeine is widely available and
inexpensive, but presents potential lack of efficacy and/or safety problems in an unpredictable A4
proportion of patients. Although access to strong opioids is variable, price is not generally a
significant barrier.
Uncertainty: none.

Feasibility
Child-appropriate dosage forms for opioids are available with the exception of very young infants.
Liquid preparations allow for easier dose titration, but concern about cost, stability, portability and A5
storage remain.
The dosage forms reported in the 2010 EMLc are as follows:
• granules: modified release (to mix with water), 20 mg, 30 mg, 60 mg, 100 mg, 200 mg
• injection: 10 mg (morphine hydrochloride or morphine sulfate) in 1 ml ampoule
• oral liquid: 10 mg (morphine hydrochloride or morphine sulfate)/5 ml
• tablet: 10 mg (morphine sulfate)
• tablet (prolonged release): 10 mg, 30 mg, 60 mg, 100 mg, 200 mg (morphine sulfate). A6
Strong opioids are not available in all countries.
Uncertainty: none.

Research agenda
1. Research on potential alternatives to codeine as a second step in a three-step approach is
needed.
2. Long-term safety data of non-steroidal anti-inflammatory drugs and paracetamol is needed. A7

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