[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [Opioids and antagonists](https://durgical.com/en/pharmacology/classes/opioids-and-antagonists/) › Codeine

[Pharmacology](https://durgical.com/en/pharmacology/) · [Opioids and antagonists](https://durgical.com/en/pharmacology/classes/opioids-and-antagonists/)

# Codeine

A weak opioid for mild to moderate pain and cough. It is a prodrug: CYP2D6 turns it into morphine, which makes it dangerous in ultra-rapid metabolisers.

Updated 2026-11-01

- Class: [Opioids and antagonists](https://durgical.com/en/pharmacology/classes/opioids-and-antagonists/)
- Receptor: μ-opioid receptor (through the morphine it forms)
- ATC code: R05DA04
- WHO Model List of Essential Medicines

## ⚠ High-alert medication

An error with this medicine can cause serious harm: double checks and protocols are used.

◎**μ-opioid receptor (through the morphine it forms)**Codeine

ⓘ The figure shows morphine, codeine's active metabolite, in the μ receptor bound to its Gi protein; the viewer crops the image to the receptor.

**Target in 3D:** μ-opioid receptor (through the morphine it forms). PDB structure 8EF6 (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/8EF6) · Drag to rotate · pinch to zoom

## Mechanism of action

Codeine (3-methylmorphine) has little affinity for the μ receptor. Its pain relief depends on hepatic CYP2D6 O-demethylating it to morphine, which activates the μ receptor. Because of CYP2D6 polymorphisms, poor metabolisers get little analgesia and ultra-rapid metabolisers make too much morphine, with a risk of respiratory depression. It also suppresses the cough reflex in the brainstem.

- Hepatic CYP2D6 turns part of the codeine into morphine
- Morphine activates the μ receptor in the pain pathway
- Less pain transmission and a weaker cough reflex
- Ultra-rapid metaboliser: excess morphine and respiratory depression

## Pharmacokinetics

**Absorption**
Well absorbed by mouth.

**Metabolism**
Liver: mostly glucuronidation to codeine-6-glucuronide; a part becomes morphine (CYP2D6, active) and another norcodeine (CYP3A4).

**Elimination**
Kidney, as metabolites.

## Indications

- Mild to moderate pain when other analgesics are not enough, often combined with paracetamol
- Cough (as an antitussive)

## Adverse effects

### Common

- Drowsiness, dizziness and sedation
- Nausea and vomiting
- Constipation
- Sweating

### Serious (rare, important)

- Life-threatening respiratory depression, above all at the start or after a dose increase
- Addiction, abuse and misuse, with risk of overdose and death
- Neonatal opioid withdrawal syndrome with prolonged use in pregnancy
- Adrenal insufficiency with prolonged use
- Severe hypotension
- Fatal respiratory depression in ultra-rapid metaboliser children, above all after tonsillectomy or adenoidectomy

## Contraindications

- Children younger than 12 years
- Postoperative management of tonsillectomy or adenoidectomy in under-18s
- Significant respiratory depression
- Acute or severe bronchial asthma without monitoring or resuscitation equipment
- Known or suspected gastrointestinal obstruction, including paralytic ileus
- Hypersensitivity to the drug
- Use of monoamine oxidase inhibitors within the last 14 days

## Key interactions

**Benzodiazepines, alcohol and other central nervous system depressants**
Add up to profound sedation, respiratory depression, coma and death.

**CYP3A4 inhibitors**
More codeine left for CYP2D6 and more morphine: a stronger or longer effect.

**CYP3A4 inducers, or stopping an inhibitor**
Less morphine: weaker pain relief or withdrawal.

**Monoamine oxidase inhibitors (current or within the last 14 days)**
Contraindicated: risk of serotonin syndrome or opioid toxicity.

## What is monitored

- Respiratory rate and sedation level
- Bowel habits
- Signs of toxicity in the breastfed infant if the mother receives it

## Administration and safety

- Check whether the product is a combination with paracetamol so that total paracetamol is not exceeded.
- Not used in children under 12 or after tonsillectomy in under-18s.
- Controlled medicine: the order is verified, every dose recorded and leftovers kept secure.

## Nursing care

- Before each dose: respiratory rate, oxygen saturation and sedation level; hold the dose and report excessive sedation or slow breathing.
- Keep naloxone at hand and teach the family to recognise an overdose.
- Prevent constipation from the start and track bowel habits.
- Prevent falls: dizziness, drowsiness and orthostatic hypotension.
- Breastfeeding is not recommended during treatment: an infant can be poisoned if the mother is an ultra-rapid metaboliser.

## Pregnancy and breastfeeding

Prolonged use in pregnancy can cause neonatal opioid withdrawal syndrome, which is expected and treatable; the newborn is watched after birth.

## Memory aid

Codeine = «morphine on credit»: CYP2D6 makes the loan. A slow bank gives no relief; an ultra-rapid one pays it all at once and the child stops breathing.

## Test yourself

Think of the answer, then tap the question to see it.

## Why can codeine be fatal in some children?

Ultra-rapid CYP2D6 metabolisers turn more codeine into morphine and can develop severe respiratory depression; so it is contraindicated under 12 and after tonsillectomy in under-18s.

## What happens to codeine analgesia in a CYP2D6 poor metaboliser?

Little morphine is formed and pain relief is poor.

## How can a CYP3A4 inhibitor increase codeine's effect?

By slowing the route to norcodeine it leaves more codeine for CYP2D6, which makes more morphine.

[Add to my cards (3)](https://durgical.app/estudiar/?add=/en/pharmacology/codeine/)

## Related drugs

- [Morphine](https://durgical.com/en/pharmacology/morphine/)
- [Tramadol](https://durgical.com/en/pharmacology/tramadol/)
- [Paracetamol](https://durgical.com/en/pharmacology/paracetamol/)

[← Back to the class: Opioids and antagonists](https://durgical.com/en/pharmacology/classes/opioids-and-antagonists/)

Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: [Codeine: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a682065.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [CODEINE SULFATE tablet](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5819bdf7-300e-45b8-8f3a-447b53656293) (DailyMed (U.S. National Library of Medicine), 2026); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 23 (McGraw Hill, 2023); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=R05DA04) (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.

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