Metabolism varies between individuals
The risk of post-surgical respiratory depression after codeine use is thought to be linked to an individual’s rate of codeine metabolism. Codeine is metabolised to morphine via the cytochrome CYP450 enzyme CYP2D6 and genetic differences in the expression of this enzyme, according to racial or ethnic group, determine the extent to which codeine is metabolised. Patients considered to be ultra-rapid metabolisers will have higher levels of the active metabolite, which can lead to toxic effects.
Advice from the MHRA
The MHRA has issued the following advice for healthcare professionals:
- Remain aware that different patients may respond differently to codeine.
- Advise carers of patients taking codeine to seek professional help if symptoms of toxicity occur (eg, reduced levels of consciousness, lack of appetite, somnolence, constipation, respiratory depression, pin-point pupils, nausea and vomiting).
A European Medicines Agency review of the safety of codeine-containing medicines licensed for pain relief in children is ongoing.