codeine + ibuprofen: clinical use

Prescribing considerations

• Reserve for acute moderate pain inadequately relieved by appropriate single-ingredient analgesics.
• Review gastrointestinal, renal, hepatic, cardiovascular, respiratory and bleeding risks, including concurrent medicines.
• Assess vulnerability to opioid toxicity, misuse or dependence.
• Use particular caution in older or debilitated patients, dehydration, asthma, inflammatory bowel disease and previous ulceration.
• Persistent or worsening pain requires reassessment.

Contraindications and cautions

• Hypersensitivity to codeine, ibuprofen, aspirin or another NSAID, including previous NSAID-associated asthma, urticaria, rhinitis or angioedema
• Active or recurrent peptic ulcer or bleeding, or previous NSAID-associated gastrointestinal bleeding or perforation
• Severe renal, hepatic or heart failure
• Respiratory depression, chronic constipation or raised intracranial pressure
• Known CYP2D6 ultra-rapid metabolism
• Concurrent or recent MAOI use
• Children younger than 12 years; and patients younger than 18 years after tonsillectomy or adenoidectomy for obstructive sleep apnoea
• Last trimester of pregnancy and breastfeeding

Monitoring

• Assess pain response and whether continued treatment remains appropriate.
• Watch for sedation, respiratory depression, constipation, misuse, tolerance, withdrawal and hyperalgesia.
• Monitor for gastrointestinal bleeding, fluid retention, worsening blood pressure, renal impairment and severe skin reactions in at-risk patients.
• Where clinically indicated, consider renal function, hepatic function, blood pressure and blood count.
• After exposure for several days from 20 weeks of pregnancy, specialist assessment may include fetal amniotic-fluid and ductus-arteriosus monitoring.

Clinical pharmacology

Ibuprofen reversibly inhibits cyclo-oxygenase-mediated prostaglandin synthesis and platelet aggregation. Codeine has low intrinsic affinity for μ-opioid receptors and relies partly on CYP2D6 conversion to morphine, causing clinically important variability in analgesia and toxicity.

Formulation and product differences

• Selected products are immediate-release oral tablets containing ibuprofen with codeine phosphate.
• The Boots product is a white, capsule-shaped film-coated tablet embossed “I +”; Nurofen Plus is described as a tablet.
• The codeine component may be described as codeine phosphate or codeine phosphate hemihydrate, depending on the product documentation.

Tablet

Route: Oral

Strengths: 200 mg + 12.8 mg