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.

Recommendation

Do not use codeine-containing medicines in children under 12 as it is associated with a risk of respiratory side effects related to opiate toxicity. Codeine is not recommended for adolescents (12 to 18) who have problems with breathing eg neurorespiratory problems.

Contraindicated in all patients of any age known to be CYP2D6 ultra-rapid metabolisers (esp common in Africans, else 1-2%) who convert codeine into morphine.

CYP2D6 substrates include tricyclics, SSRIs, opioids, antipsychotics, beta-blockers, Chlorphenamine (!) among others. Rifampicin and dexamethasone are the only inducers, inhibitors include SSRIs. Effect depends on whether a drug needs cytochrome P450 to activate it in the first place, and whether oxidation products are more or less active than original form.

[MHRA]