Clinical beta

FMBM is currently in clinical beta. Content is for professional review/testing and must not replace local protocols, senior clinical judgment, or official prescribing references.

Drug Monograph

Codeine

USE IF: Mild—moderate pain (step 2), dry cough, short-term use only

AVOID IF: Children <12, breastfeeding, CYP2D6 URM/PM, MAOI use

Codeine

Weak opioid (prodrug to morphine via CYP2D6)

OpioidProdrugCYP2D6AntitussiveCombination products

Indication

Mild–moderate pain (step 2), dry cough, short-term use only

At a glance

INDICATION -> Step-up analgesic when paracetamol/NSAIDs are insufficient

ADULT DOSE -> 30–60 mg q4–6h

MAX DOSE -> 240 mg/day (EMA preferred)

CONTRA -> Children <12, breastfeeding, CYP2D6 URM/PM concerns, MAOI use

ANTIDOTE -> Naloxone

Quick facts

Onset

30–45 min (PO)

Duration

Peak ~1 h; duration 4–6 h; half-life 2.5–4 h.

Routes

PO, PR, IM (rare)

Pregnancy

Use short-term only

Renal

Reduce dose

Hepatic

Avoid severe impairment

Do not miss

Time to action: 30—45 min

Max dose

  • 240 mg/day.

Critical risks

  • CYP2D6 ultrarapid metabolizer toxicity.
  • Respiratory depression.
  • Infant death risk in breastfeeding exposure.

Antidote

  • Naloxone.

High-risk scenarios

  • CYP2D6 inhibitors.
  • OSA.
  • Children.
  • Elderly.

Key interactions

  • SSRIs (CYP2D6 impact).
  • MAOI.
  • Benzodiazepines.

Indications

Primary

  • Mild–moderate pain
  • Cough suppression

Secondary

  • Step-down analgesia
  • Cancer pain step 2

Other

  • Diarrhea (limited use)

Dosing

Standard: 30—60 mg q4—6h

Max daily dose

  • 240 mg/day (EMA preferred).
  • Use short-term only; avoid prolonged use due to dependence and variable metabolism.

Adult - PO

  • Pain: 30–60 mg q4–6h (max 240 mg/day).
  • Cough: 15–30 mg q4–6h.

Adult - IV

  • Not used.

Pediatric

  • <12: contraindicated.
  • 12–18: 0.5–1 mg/kg q6h (max 240 mg/day); avoid in OSA.

Renal adjustment

  • CrCl 10–50: reduce dose by 25%.
  • CrCl <10: reduce by 50% or avoid.

Hepatic adjustment

  • Mild impairment: reduce dose.
  • Severe impairment: avoid.

Warnings

Clinical warnings

  • Respiratory depression (black box context).
  • CYP2D6 variability can cause toxicity or no effect.
  • Addiction/misuse risk.
  • Neonatal withdrawal.
  • Serotonin syndrome risk with MAOI.
  • Constipation (class effect).
  • Combination-product toxicity risk (paracetamol).

Adverse effects

  • Common: nausea, constipation, drowsiness, dizziness.
  • Serious: respiratory depression, severe sedation, dependence.

Contraindications / caution

Do not use

  • Children <12.
  • Breastfeeding.
  • Post-tonsillectomy/adenoidectomy (<=18 years) (absolute contraindication).
  • CYP2D6 ultrarapid metabolizers are contraindicated (risk of morphine toxicity).
  • MAOI use.
  • Respiratory depression.

Use caution / avoid high doses

  • CYP2D6 poor metabolizer (reduced effect).
  • Elderly.
  • CKD.
  • Liver disease.
  • OSA.

Drug interactions

  • CYP2D6 inhibitors (e.g., fluoxetine, paroxetine) significantly reduce analgesic effect -> avoid or switch opioid.
  • MAOI -> contraindicated.
  • Benzodiazepines -> increased respiratory depression risk.
  • Alcohol -> additive CNS depression.
  • Warfarin -> INR changes (especially with combo products).

Special populations

Pediatrics

<12 contraindicated; 12–18 only with strict caution.

Pregnancy

Short-term use only; avoid near term.

Breastfeeding

CONTRAINDICATED.

Elderly

Start low (e.g., 15 mg q6h).

Liver disease

Avoid severe impairment.

Renal impairment

Reduce dose; avoid severe renal dysfunction when possible.

Administration

  • PO preferred.
  • Take with food if GI upset.
  • Always calculate total paracetamol dose in combination products.
  • Keep minimum 4–6 h between doses.

Monitoring

  • Renal function.
  • LFTs.
  • INR when on warfarin.
  • Respiratory rate.
  • Sedation level.
  • Pain control.
  • Bowel function.
  • Total paracetamol intake from all products.

Overdose / toxicity

IF SUSPECTED CODEINE OVERDOSE: ABC first.

Recognition

  • Risk rises with doses >240 mg/day.
  • Miosis + respiratory depression + coma.
  • Consider coexisting paracetamol toxicity in combination products.

Immediate actions

  • Naloxone for opioid toxicity.
  • Activated charcoal within <=2 h when airway is protected.
  • Start NAC if paracetamol overdose is suspected/confirmed.

Antidote

  • Naloxone.

Decontamination

  • Activated charcoal <=2 h if appropriate.

Escalation

  • Naloxone infusion for recurrent toxicity/re-narcotization.

Clinical pearls

Common mistakes, resistance logic, and bedside traps

Genetics first

  • Most unpredictable opioid (genetics-driven).
  • URM -> toxicity; PM -> little/no effect.

Do not chase dose

  • Do NOT keep increasing dose if ineffective; switch agent.

Breastfeeding

  • Avoid in breastfeeding (absolute contraindication).

Hidden APAP

  • Combination products can cause hidden paracetamol overdose.

Short course

  • Aim for short duration (e.g., max 3 days for acute pain when possible).

Pain severity

  • Not suitable for severe pain.

Regional misuse risk

  • High misuse potential in Gulf region.

Pharmacokinetics

  • High oral absorption (~90%).
  • Hepatic metabolism via CYP2D6 and CYP3A4.
  • Renal excretion.
  • Active metabolite: morphine.

Mechanism of action

  • Prodrug converted by CYP2D6 to morphine.
  • Morphine metabolite is a mu-opioid receptor agonist.
  • Analgesia is genotype-dependent.

Common brand names

Saudi Arabia

Fevadol Plus · Solpadeine · Actifed Compound · Codeine phosphate (generic)

Global

Tylenol #3 / #4 · Panadeine · Co-codamol · Codeine Contin

Common trade names are curated examples only — formulations and availability vary. Verify the exact product name with your local pharmacy and national regulator before prescribing or dispensing.

Country practice notes

  • Widely used in Gulf in combination products (Solpadeine, Fevadol Plus).
  • SFDA controlled-drug framework with stricter regulation updates.
  • High CYP2D6 variability in MENA can cause unpredictable response/toxicity.
  • Misuse/dependence is a recognized public-health issue in Saudi Arabia.
  • OTC availability is progressively restricted across GCC.

Saudi Arabia — confirm with local formulary.