Codeine not to be used in children under twelve: MHRA
11 July 2013
Codeine-containing medicines should only be used in children over 12 years old to treat acute (short lived) moderate pain, and only if it cannot be relieved by other painkillers such as paracetamol or ibuprofen, the Medicines and Healthcare products Regulatory Agency (MHRA) has confirmed, following completion of a European review.
Where it is used in children, it should be used at the lowest effective dose and only for the shortest period of time recommended by the doctor. This is because some patients may be at an increased risk of rare but serious adverse reactions as a result of the way the body handles codeine and younger children may be particularly susceptible.
It has also been concluded that codeine should not be used at all in any patient under 18 years old who undergoes the removal of tonsils or adenoids for the treatment of sleep apnoea. This is due to an increased risk of severe breathing difficulties.
'This is important new advice for the use of codeine for pain relief in children,' said Dr Sarah Branch, Deputy Director of the MHRA’s Vigilance and Risk Management of Medicines Division. 'Whilst codeine is not commonly used in children, the evidence is clear that there is risk of side effects in children, and other painkillers should be used whenever possible.'
Codeine is converted to morphine in the liver by the CYP2D6 enzyme. There are many genetic variations of CYP2D6, which affect the extent of this conversion in individuals. Different plasma morphine concentrations in patients’ blood leads not only to different levels of pain relief, but also to a variable and unpredictable risk of side effects due to morphine’s action on the brain and respiratory centre.
A European review of the safety of codeine-containing medicines licensed for pain relief in children (age 0–18 years) began in October 2012. This review was triggered by concerns of an increased risk of morphine toxicity when susceptible children receive codeine for pain after surgery. These concerns follow the reporting of three fatalities and one life-threatening case of respiratory depression in children given codeine after tonsillectomy or adenoidectomy in the treatment of obstructive sleep apnoea.
The conclusions of the review (see http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2013/06/news_detail_00 1813.jsp&mid=WC0b01ac058004d5c1) are reflected in the following new advice for healthcare professionals:
* Codeine should only be used to relieve acute moderate pain in children older than twelve years and only if it cannot be relieved by other painkillers such as paracetamol or ibuprofen
* Codeine is contraindicated in all children (ie, younger than 18 years) who undergo tonsillectomy or adenoidectomy (or both) for obstructive sleep apnoea
* Codeine is not recommended for use in children whose breathing might be compromised, including those with: neuromuscular disorders; severe cardiac or respiratory conditions; upper respiratory or lung infections; multiple trauma; or extensive surgical procedures. The symptoms of morphine toxicity may be increased in these settings.
* In children aged 12–18 years, the maximum daily dose should not exceed 240 mg. This may be taken in divided doses, up to four times a day at intervals of no less than six hours. It should be used at the lowest effective dose for the shortest period. Duration of treatment should be limited to 3 days and if no effective pain relief is achieved, treatment should be reviewed by a physician
* Information should be given to parents and caregivers on how to recognise the signs of morphine toxicity, and advice should be given to stop giving the child codeine and to seek medical attention immediately if their child is showing these signs or symptoms
* Symptoms of codeine toxicity include: reduced levels of consciousness; somnolence; respiratory depression; ‘pin-point’ pupils; lack of appetite; constipation; or nausea and vomiting
* Codeine is contraindicated in all patients of any age known to be CYP2D6 ultra-rapid metabolisers
* Codeine should not be used by breastfeeding mothers because it can pass to the baby through breast milk and potentially cause harm