Codeine phosphate

Class: analgesic – opioid (metabolised to morphine, noting that there is individual variability in hepatic metabolism)

Indications (NB some may be unlicensed): step 2 in the WHO analgesic ladder (pain), cough, diarrhoea

Contraindications/cautions: avoid use with other opioid analgesics; caution renal impairment; hepatic impairment

Adverse reactions: as for morphine – very constipating; drowsiness

Metabolism/clearance: metabolised by metabolising enzyme CYP2D6 mainly in the liver to an active metabolite – morphine. Minor metabolism by 3A. Caution in ultra-rapid metabolisers – may result in morphine toxicity; poor metabolisers may experience reduced therapeutic effect

Interactions:

• decreased clinical effect/toxicity of codeine (due to decreased blood concentrations of morphine – an active metabolite) may occur with some CYP metabolising enzyme inhibitors (see above) e.g. bupropion, fluoxetine, paroxetine (not citalopram), quinine
• additive CNS effects with other CNS depressants e.g. benzodiazepines (e.g. lorazepam), phenothiazines (e.g. chlorpromazine), tricyclic antidepressants (e.g. amitriptyline), other opioids, alcohol
• inhibition of the antidiarrhoeal effects of codeine may occur with concomitant metoclopramide/domperidone

Syringe driver: N/A

Mechanism of action: metabolised to morphine (analgesic action) and other active metabolites; codeine reduces intestinal motility by binding opioid receptors in intestinal tract; cough suppression by acting on cough centre in the medulla

Peak effect: 2 to 4 hours Duration: 4 to 8 hours

Notes:

• combination products are not recommended
• 10% of dose is converted to morphine in “normal” metabolisers i.e. 60 mg codeine = 6 mg morphine
• 5 to 10% of the Caucasian population may be unable to metabolise codeine to morphine
• combination with other opioids is illogical
• dihydrocodeine slow release is available although it is not often used in palliative care