Codeine Phosphate

How it works

Codeine is a prodrug metabolised by CYP2D6 to morphine, which acts as a mu-opioid receptor agonist to produce analgesia; some direct opioid effect also contributes.

Prescribing in practice

• Ultra-rapid CYP2D6 metabolisers convert codeine to morphine excessively; it is contraindicated in breastfeeding mothers and in children under twelve, and is not recommended after tonsillectomy/adenoidectomy in under-18s with obstructive sleep apnoea, owing to fatal respiratory depression.
• It carries the usual opioid risks of respiratory depression, dependence, tolerance and constipation, with additive sedation alongside other CNS depressants.
• Efficacy is unpredictable as CYP2D6 poor metabolisers gain little analgesia while CYP2D6 inhibitors reduce conversion to morphine.

Monitoring

Monitor pain control, sedation, respiratory status and bowel function, and review for signs of dependence with prolonged use.

Counselling the patient

• Do not exceed the prescribed dose and avoid combining with alcohol or other sedating medicines.
• Take a laxative or increase fibre and fluids if constipation occurs.
• Breastfeeding mothers should not use it; seek advice about excessive drowsiness in the infant.

Evidence & guidelines

The MHRA has restricted codeine use in children and breastfeeding women because of the risk of morphine toxicity in ultra-rapid metabolisers.