Analgesics contraindicated in children

Restricted use in children because of reports of morphine toxicity : MHRA

September 6, 2013 – 11:04

Relax centrum

Article date: July 2013 Summary
Codeine should only be used to relieve acute moderate pain in children older than 12 years and only if it cannot be relieved by other painkillers such as paracetamol or ibuprofen alone.
Furthermore, a significant risk of serious and life-threatening adverse reactions has been identified in children with obstructive sleep apnoea who received codeine after tonsillectomy or adenoidectomy (or both). Codeine is now contraindicated in all children younger than 18 years who undergo these procedures for obstructive sleep apnoea

Codeine is used for pain relief in adults and children and is considered to be suitable for persistent pain of up to moderate intensity. It is commonly used in combination with other drugs—mainly paracetamol, but also aspirin, caffeine, or ibuprofen. However, despite its established use, there remains substantial lack of knowledge about its safety and efficacy—particularly in the paediatric population.


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. People can be classified as: poor; intermediate; extensive; or ultra-rapid metabolisers. Different plasma morphine concentrations in patients’ blood lead 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.

Poor metabolisers convert very little codeine into morphine and therefore have little or no pain relief. 7–10% of Caucasians are poor metabolisers, but this proportion varies with ethnic origin.

Individuals who are ultra-rapid metabolisers or extensive metabolisers have an excessive amount of morphine in their blood, which can lead to severe side effects due to its effects on the brain and on breathing. Prevalence of ultra-rapid metabolisers also varies by ethnic origin: it is less common in northern European countries (including the UK) and is more common in Spain, Italy, Greece, Africa, and the Middle East (see table).


Prevalence of ultra-rapid metabolisers (%)

African or Ethiopian


African American










Northern European


European review

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.Ciszkowski C, et al. N Engl J Med 2009; 361: 827–28. Kelly LE, et al. Pediatrics 2012; 129: 1343–47.


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