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Codeine + bupropion/fluoxetine/paroxetine — ↓ activation

Interaction at a glance

• Analgesia may fail despite codeine dose
• Do not chase effect with more codeine

Mechanism

• Codeine needs CYP2D6 → morphine
• Strong 2D6 inhibitors block activation
• morphine formation falls

Management

• Analgesia may fail despite codeine dose

Management / timing

• Do not chase effect with more codeine
• Use analgesic not dependent on CYP2D6

Self-check

• What is the main clinical risk of Codeine + bupropion/fluoxetine/paroxetine?
  Analgesia may fail despite codeine dose.
• What is the main mechanism of the Codeine + bupropion/fluoxetine/paroxetine interaction?
  Strong 2D6 inhibitors block activation; morphine formation falls.

Drugs in this interaction (4)

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