Overview
Codeine phosphate is an opioid analgesic used for the management of mild to moderate pain when alternative treatments are inadequate. It works by binding to opioid receptors in the central nervous system to reduce pain perception. Due to risks of addiction, respiratory depression, and overdose, it should be prescribed at the lowest effective dose for the shortest duration.
Mechanism of Action
Codeine is a prodrug that is metabolized by CYP2D6 to morphine, which acts as an agonist at mu-opioid receptors in the central nervous system. This binding inhibits neurotransmitter release, reducing pain signal transmission and altering pain perception.
Indications
- Management of mild to moderate pain where treatment with an opioid is appropriate and alternative treatments are inadequate
Common Doses
- Codeine 15 mg/Acetaminophen 300 mg
- Codeine 30 mg/Acetaminophen 300 mg
- Codeine 60 mg/Acetaminophen 300 mg
Dosage
Typical adult dosage: Codeine 15-60 mg combined with acetaminophen 300-1000 mg every 4 hours as needed for pain. Maximum daily dose: Codeine 360 mg, Acetaminophen 4000 mg. Use lowest effective dose for shortest duration.
Contraindications
- Children younger than 12 years
- Post-operative management in children younger than 18 years following tonsillectomy/adenoidectomy
- Significant respiratory depression
- Acute or severe bronchial asthma in unmonitored setting
- Concurrent use of MAOIs or within 14 days
- Known or suspected gastrointestinal obstruction
- Hypersensitivity to codeine or acetaminophen
Side Effects
- Drowsiness, dizziness, sedation
- Nausea, vomiting, constipation
- Respiratory depression
- Pruritus, rash, sweating
- Hypotension, bradycardia
- Serotonin syndrome (with serotonergic drugs)
- Adrenal insufficiency
- Seizures
- Withdrawal symptoms with abrupt discontinuation
Interactions
- CYP2D6 inhibitors (e.g., paroxetine, fluoxetine) - may reduce efficacy or cause withdrawal
- CYP3A4 inhibitors (e.g., ketoconazole, erythromycin) - may increase toxicity
- Benzodiazepines and other CNS depressants - increased risk of respiratory depression
- MAOIs - risk of serotonin syndrome or opioid toxicity
- Serotonergic drugs - risk of serotonin syndrome
Counseling Points
- Take only as prescribed; do not increase dose without medical advice
- Avoid alcohol and other CNS depressants
- Recognize signs of overdose: extreme sleepiness, confusion, shallow breathing
- Store securely away from children and others
- Dispose of unused medication properly
- Use lowest effective dose for shortest duration
- Have naloxone available if at risk for overdose