[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/) › Hydrocodone

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

# Hydrocodone

A semi-synthetic μ agonist for severe pain and, in some countries, cough; often combined with paracetamol. Part of it is activated to hydromorphone.

Updated 2026-11-01

- Class: [Opioids and antagonists](https://durgical.com/en/pharmacology/classes/opioids-and-antagonists/)
- Receptor: μ-opioid receptor
- ATC code: R05DA03

## ⚠ High-alert medication

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

◎**μ-opioid receptor**Hydrocodone

ⓘ The figure shows morphine in the μ receptor; hydrocodone, a codeine derivative, occupies the same site. There is no structure of hydrocodone in the receptor.

**Target in 3D:** μ-opioid receptor. 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

Hydrocodone is a semi-synthetic μ agonist related to codeine. It activates the μ receptor and reduces pain transmission; it also suppresses the cough reflex. In the liver CYP2D6 converts it to hydromorphone, which is more potent, and CYP3A4 to norhydrocodone.

- Activates the μ receptor in the pain pathway
- CYP2D6 makes hydromorphone, a more potent agonist
- Less pain transmission and a weaker cough reflex
- CYP3A4 inactivates it: its inhibitors raise levels

## Pharmacokinetics

**Absorption**
By mouth; immediate-release (often with paracetamol) and extended-release forms exist.

**Metabolism**
Liver: CYP3A4 to norhydrocodone and CYP2D6 to hydromorphone.

## Indications

- Severe, persistent pain needing an opioid when other options are not enough (extended-release form)
- Acute pain, in combination with paracetamol
- Cough (in antitussive combinations)

## Adverse effects

### Common

- Nausea, vomiting and abdominal pain
- Sweating
- Lower sexual desire or erectile dysfunction

### 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

## Contraindications

- 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

## Key interactions

**CYP3A4 inhibitors (macrolides, azoles, ritonavir), or stopping inducers (rifampicin, carbamazepine, phenytoin)**
Raise opioid levels and can cause a fatal overdose.

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

## What is monitored

- Respiratory rate and sedation
- Bowel habits
- Total paracetamol if it is a combination product

## Administration and safety

- Extended-release capsules are swallowed whole; crushing, chewing or dissolving the beads releases a potentially fatal dose.
- With combination products, paracetamol from all sources is added up.
- 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.
- Teach the patient to lock the medicine away and dispose of leftovers safely.

## 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

HYDROcodone = «a codone that turns into HYDRO(morphone)»: CYP2D6 powers it up, CYP3A4 switches it off.

## Test yourself

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

## Which more potent metabolite does hydrocodone form, and through which enzyme?

Hydromorphone, through CYP2D6.

## What extra risk does combining hydrocodone with paracetamol carry?

Paracetamol hepatotoxicity if several sources of it are added up.

## What happens if extended-release hydrocodone capsules are crushed?

The whole dose is released at once and a fatal overdose can follow.

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## Related drugs

- [Oxycodone](https://durgical.com/en/pharmacology/oxycodone/)
- [Hydromorphone](https://durgical.com/en/pharmacology/hydromorphone/)
- [Codeine](https://durgical.com/en/pharmacology/codeine/)

[← 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: [Hydrocodone: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a614045.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [HYDROCODONE BITARTRATE capsule, extended release](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a7b8ea07-e926-f0a5-c20d-92f23ed350d0) (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=R05DA03) (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake

Representative model, for educational purposes only.

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