codeine phosphate + paracetamol: clinical use

Prescribing considerations

• Confirm that prescription, pharmacy and self-care products do not also contain paracetamol or another opioid.
• Assess respiratory disease, hepatic and renal function, bowel-obstruction risk, head injury, seizure history, alcohol use, frailty and concurrent CNS depressants.
• Assess individual and family histories of substance-use disorder and relevant mental-health conditions; repeated codeine exposure can cause tolerance, dependence and opioid-use disorder.
• Analgesic failure or disproportionate toxicity may reflect CYP2D6 phenotype. Known ultra-rapid metabolism is contraindicated.
• Review ongoing need, function, adverse effects, tolerance, hyperalgesia and evidence of dependence. Plan gradual withdrawal after prolonged regular exposure.
• Apply the contraindications and excipient warnings for the selected product because licences differ.

Contraindications and cautions

• Hypersensitivity to either active ingredient or product excipients.
• Known CYP2D6 ultra-rapid metabolism.
• Breastfeeding.
• Children younger than 12 years.
• Use after tonsillectomy or adenoidectomy for obstructive sleep apnoea in anyone younger than 18 years.
• Acute respiratory depression; selected products also contraindicate acute asthma, obstructive airway disease or other situations in which opioids should not be used.
• The selected capsule product contraindicates moderate-to-severe renal or hepatic impairment and lists further restrictions including acute alcoholism, head injury, raised intracranial pressure and obstructive gastrointestinal conditions.

Monitoring

• Observe for sedation and respiratory depression, particularly with other CNS depressants, respiratory compromise or frailty.
• Monitor pain response, function, adverse effects, tolerance, hyperalgesia, dependence and drug-seeking behaviour when treatment continues.
• For prolonged use, selected product information advises monitoring full blood count and liver and renal function.
• Consider acid-base assessment for unexplained high-anion-gap metabolic acidosis, especially with severe illness, renal impairment, malnutrition, chronic alcohol use or flucloxacillin.

Clinical pharmacology

Paracetamol is an analgesic and antipyretic acting predominantly through central pathways. Codeine is a weak opioid prodrug whose analgesic activity depends substantially on CYP2D6 conversion to morphine; genetic variability contributes to differences in efficacy and toxicity.

Formulation and product differences

• Selected products include conventional tablets, hard capsules, effervescent tablets and film-coated Migraleve Yellow tablets.
• Effervescent tablets must be dissolved before use and may contain clinically relevant sodium and sorbitol; check the individual product information where sodium restriction or hereditary fructose intolerance is relevant.
• Migraleve Yellow contains codeine and paracetamol. In combination Migraleve packs, Pink tablets additionally contain buclizine, so the colours are not interchangeable.
• Licensed indications and some contraindications differ between selected products.

Capsule

Route: Oral

Strengths: 15 mg + 500 mg, 30 mg + 500 mg

Tablet

Route: Oral

Strengths: 15 mg + 500 mg, 30 mg + 500 mg