see also:

• opiates and opioids

• codeine phosphate is an opioid analgesic which is also sometimes used as an antitussive agent.
• its analgesic effect is thought to be due to its partial metabolic conversion to morphine
• structurally similar to morphine and oxycodone so should be avoided in patients with hypersensitivities to these
• codeine is metabolised in the liver via:
  • glucuronidation to codeine-6-glucuronide which is the main metabolic pathway
  • O-demethylation to morphine catalysed by CYP2D6 (~10% of the codeine dose in most patients) is the main therapeutic pathway
    • unfortunately, 5-10% of the Caucasian population are deficient in this pathway “slow metabolisers” which means in these patients they will not get the same analgesic benefit.
      • <1% of those from eastern Asia are deficient, while up to 20% of Africans are.
    • furthermore, some are ultrafast metabolisers increasing risk of respiratory depression:
      • 5-30% of Africans
      • up to 20% of Arabians
      • 7-10% of southern Europeans
      • 1-4% of western Europeans
    • patients on CYP2D6 inhibitors such as many antidepressants, may also be slow metabolisers
    • patients on enzyme inducers such as phenytoin may have increased effects as they metabolise codeine faster to the active form
  • N-demethylation to normorphine catalysed by CYP3A4
  • N-demethylation to norcodeine then glucuronidation to norcodeine glucuronide, or O-demethylation to normorphine
• plasma half-life of codeine is 2-4 hours

• adults 30mg every 4-6hrs when used as codeine phosphate tablets
• more commonly it is used in tablets containing 8-15mg codeine with another analgesic such as paracetamol (eg. Panadeine or Panadeine forte) or aspirin (eg. Aspalgin)

• see opiates and opioids
• common dose related adverse effects include nausea, vomting, constipation and dizziness
• elderly are particularly susceptible to sedation, confusion and increased falls
• slow metabolisers are at risk of inadequate analgesia
• patients with obstructive sleep apnoea, or COPD with risk of type 2 respiratory failure, and those given high dose or who are ultrafast metabolisers, have risk of life-threatening respiratory depression, particularly when used with other respiratory depressant drugs such as benzodiazepines
• avoid in lactating mothers as there have been cases of neonatal death which may be related to mother being an ultrafast metaboliser
• do NOT use cough suppressant doses in those under the age of 18 years as risks outweigh the benefits
• avoid in young children