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Opioid Analgesia Pregnancy: Avoid in third trimester — neonatal opioid withdrawal and respiratory depression risk; use with caution and only if essential

Codeine Phosphate

Brand names: Codeine Linctus, Codeine Phosphate Tablets

Adult dose

Dose: 30–60 mg
Route: Oral
Frequency: Every 4–6 hours
Max: 240 mg/24h
Use with caution in pregnancy — avoid at term (neonatal respiratory depression, neonatal abstinence syndrome). Short-term use acceptable in second trimester for severe pain where alternatives are inadequate.

Paediatric dose

Dose: 0.5–1 mg/kg mg/kg
Route: Oral
Frequency: Every 4–6 hours
Max: 60 mg per dose; 240 mg/day
MHRA 2013: codeine contraindicated in children <12 years for pain relief; contraindicated in children 12–18 years after tonsillectomy/adenoidectomy for OSA — ultra-rapid CYP2D6 metabolisers at risk of morphine toxicity

Dose adjustments

Renal

Reduce dose and increase interval in renal impairment — active metabolite (morphine-6-glucuronide) accumulates

Hepatic

Use with caution — impaired conversion and clearance

Paediatric weight-based calculator

MHRA 2013: codeine contraindicated in children <12 years for pain relief; contraindicated in children 12–18 years after tonsillectomy/adenoidectomy for OSA — ultra-rapid CYP2D6 metabolisers at risk of morphine toxicity

Clinical pearls

  • MHRA 2013: codeine contraindicated in breastfeeding — ultra-rapid CYP2D6 metabolisers can produce fatal morphine concentrations in breast milk
  • MHRA 2013: contraindicated in children <12 years for pain; contraindicated 12–18 years post-tonsillectomy/adenoidectomy
  • Avoid in third trimester — neonatal opioid withdrawal syndrome and respiratory depression at birth
  • Short-term use in second trimester acceptable when paracetamol inadequate; document clinical reasoning
  • ~10% of population are ultra-rapid CYP2D6 metabolisers (North African/Middle Eastern heritage higher prevalence)

Contraindications

  • Ultra-rapid CYP2D6 metabolisers (risk of morphine toxicity)
  • Breastfeeding (MHRA 2013)
  • Children <12 years for pain
  • Near term in pregnancy
  • Respiratory depression

Side effects

  • Constipation
  • Nausea
  • Vomiting
  • Sedation
  • Respiratory depression (overdose)
  • Neonatal abstinence syndrome (prenatal exposure)

Interactions

  • MAOIs — avoid concurrent use (serotonin syndrome risk)
  • CNS depressants — additive sedation
  • CYP2D6 inhibitors (fluoxetine, paroxetine) — reduce conversion to morphine

Monitoring

  • Respiratory rate
  • Level of sedation
  • Neonatal wellbeing if used near term

Reference: BNFc; BNF 90; MHRA Drug Safety Update (2013) Codeine; BNFc. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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