WC500185968

Regulatory details:
PRAC Rapporteur: Julie Williams (UK)
PRAC Co-Rapporteur: Martin Huber (DE)
Administrative details:
Procedure number: EMEA/H/A-31/1394
MAH(s): various
Background
A referral procedure under Article 31 of Directive 2001/83/EC for codeine-containing medicines (see
PRAC Minutes February 2015), when used for the treatment of cough and/or cold in paediatric
patients, is to be concluded. A final assessment of the data submitted was produced by the
Rapporteurs according to the agreed timetable.
Discussion
The PRAC discussed the conclusions reached by the Rapporteurs together with the available evidence
on the risk of opioid toxicity after exposure to codeine when used in the treatment of cough and/or
cold in paediatric patients. The opinion from the Paediatric Committee (PDCO) and responses from the
Healthcare Professionals’ organisations (HCPOs), consulted during the procedure, were also taken into
account.
Based on the available data, the PRAC considered that the use of codeine in pain relief could be
associated with serious adverse events of opioid toxicity due to the variable and unpredictable
metabolism of codeine to morphine and that children below 12 years are at risk of life-threatening
respiratory depression and those who are ultra-rapid metabolisers are at special risk.
The PRAC also noted that there was limited evidence supporting the efficacy of codeine in cough and
cold and that these were generally self-limiting conditions in children. Treatment guidelines
recommend treatment of persistent chronic cough in paediatric patients based on aetiology. Having
considered the available evidence, the PRAC concluded that the use of codeine-containing medicinal
products for the treatment of cough and/or cold in the paediatric population is not recommended due
to the nature of the conditions and the views of clinical experts. The PRAC considered that the current
evidence suggested that children below 12 years with ultra-rapid metaboliser status are at special risk
of life-threatening respiratory depression and therefore, concluded that the use of codeine-containing
medicinal products for the treatment of cough and/or cold is contraindicated in children below 12
years. The PRAC further considered that the use of codeine is not recommended in children aged 12
years to 18 years with compromised respiratory function. In line with the restrictions introduced as an
outcome of the Article 31 referral procedure for codeine used for pain relief in children
(EMA/350259/2013), the PRAC also concluded that all codeine-containing medicinal products for the
treatment of cough and/or cold should be contraindicated in women when breastfeeding, as well as in
patients known to be CYP2D6 1 ultra-rapid metabolisers.
As a consequence, the PRAC concluded that the benefit-risk balance of the medicinal products
containing codeine for cough and/or cold remains favourable, subject to the inclusion of the
restrictions, warnings and other agreed changes to the product information relating to use in children.
Summary of recommendation(s)/conclusions
The PRAC adopted by consensus a recommendation, to be considered by the CMDh, to vary the
marketing authorisations for codeine-containing medicines indicated for the treatment of cough in
1 Cytochrome P450 2D6
Pharmacovigilance Risk Assessment Committee (PRAC)
EMA/PRAC/257790/2015 Page 13/89