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NERVOUS SYSTEM › ANALGESICS › OPIOIDS › Opioids in combination with non-opioid analgesics
codeine and other non-opioid analgesics
N02AJ09
Forms & Strengths
- Tablets: Codeine phosphate 8 mg to 60 mg combined with acetaminophen 300 mg to 500 mg
- Tablets: Codeine phosphate 30 mg combined with aspirin 325 mg
- Oral Solution: Codeine phosphate 10 mg/5 mL combined with acetaminophen 120 mg/5 mL
Adult Dosing
- Codeine/Acetaminophen: 1 to 2 tablets every 4 hours as needed for pain
- Maximum daily dose: 4000 mg of acetaminophen and 360 mg of codeine per 24 hours
- Codeine/Aspirin: 1 to 2 tablets every 4 hours as needed, maximum 12 tablets per 24 hours
Pediatric Dosing
- Contraindicated in children under 12 years of age for all indications
- Contraindicated for post-operative management in children following tonsillectomy and/or adenoidectomy
- Not recommended in adolescents aged 12 to 18 years with compromised respiratory function
Indications
- Management of acute, moderate to moderately severe pain where non-opioid analgesics are insufficient
- Short-term relief of pain when combination opioid and non-opioid therapy is warranted
Mechanism of Action
- Codeine acts as a mu-opioid receptor agonist with weak affinity, exerting analgesic effects primarily after O-demethylation to morphine via CYP2D6
- Non-opioid analgesic component (acetaminophen or NSAID) inhibits prostaglandin synthesis centrally and peripherally to provide complementary analgesia
Contraindications
- Significant respiratory depression
- Acute or severe bronchial asthma in an unmonitored setting or absence of resuscitative equipment
- Known or suspected gastrointestinal obstruction, including paralytic ileus
- Hypersensitivity to codeine, acetaminophen, or aspirin
- Post-operative pain management in children younger than 18 years following tonsillectomy or adenoidectomy
- Known CYP2D6 ultra-rapid metabolizers
Adverse Reactions
- Central nervous system depression, somnolence, dizziness, sedation
- Respiratory depression and apnea
- Constipation, nausea, vomiting, abdominal pain
- Hypotension, orthostatic hypotension, syncope
- Hepatotoxicity associated with the acetaminophen component in high doses
- Gastric ulceration and bleeding associated with the aspirin component
Drug Interactions
- Concomitant use with CNS depressants (alcohol, benzodiazepines, other opioids) increases risk of profound sedation, respiratory depression, coma, and death
- CYP2D6 inhibitors (e.g., bupropion, fluoxetine) may decrease efficacy of codeine by reducing conversion to morphine
- CYP3A4 inducers (e.g., rifampin, carbamazepine) may increase metabolism and alter efficacy
- Use with MAO inhibitors may precipitate severe adverse reactions or central nervous system excitation
- Anticoagulants combined with the aspirin component increase bleeding risk
Curated Content: Needs Vetting Before Put to Clinical Use