[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [Nonsteroidal anti-inflammatory drugs (NSAIDs)](https://durgical.com/en/pharmacology/classes/nonsteroidal-anti-inflammatory-drugs/) › Diclofenac

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# Diclofenac

A widely used NSAID for joint pain and inflammation. It is almost as COX-2 selective as celecoxib and can harm the liver.

Updated 2026-11-01

- Class: [Nonsteroidal anti-inflammatory drugs (NSAIDs)](https://durgical.com/en/pharmacology/classes/nonsteroidal-anti-inflammatory-drugs/)
- Enzyme: Cyclooxygenase 2 (COX-2), also acting on COX-1
- ATC code: M01AB05

✂**Cyclooxygenase 2 (COX-2), also acting on COX-1**Diclofenac

ⓘ The figure shows diclofenac in the active site of mouse COX-2, which keeps the same site as the human enzyme.

**Target in 3D:** Cyclooxygenase 2 (COX-2), also acting on COX-1. PDB structure 1PXX (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/1PXX) · Drag to rotate · pinch to zoom

## Mechanism of action

Diclofenac, a phenylacetic acid derivative, inhibits the cyclooxygenases and lowers the prostaglandins of inflammation, pain and fever. Although it was not designed to be selective, its preference for COX-2 resembles that of celecoxib, so it shares the coxibs' higher thrombotic risk.

- Binds the active site of COX-2 (and, less, COX-1)
- Lowers prostaglandin synthesis in inflamed tissue
- Less nociceptor sensitisation and less inflammation
- Less vascular prostacyclin: a thrombotic tilt, like the coxibs

## Pharmacokinetics

**Absorption**
Rapid absorption; because of hepatic first-pass metabolism only about half the dose reaches the circulation. Also used topically.

**Distribution**
More than 99% bound to proteins, mainly albumin.

**Metabolism**
Liver, mainly by CYP2C9 to 4'-hydroxydiclofenac, then conjugated.

**Elimination**
Urine and bile, as metabolites.

**Half-life**
About 2 hours.

## Indications

- Osteoarthritis [Knee Osteoarthritis →](https://durgical.com/en/conditions/knee-osteoarthritis/)
- Rheumatoid arthritis [Rheumatoid arthritis →](https://durgical.com/en/conditions/rheumatoid-arthritis/)
- Ankylosing spondylitis [Ankylosing spondylitis →](https://durgical.com/en/conditions/ankylosing-spondylitis/)

## Adverse effects

### Common

- Diarrhoea, constipation, gas or bloating
- Headache and dizziness
- Ringing in the ears
- Raised liver enzymes

### Serious (rare, important)

- Cardiovascular thrombotic events (heart attack, stroke), which can appear early and increase with duration of use
- Gastrointestinal ulcer, bleeding and perforation, sometimes without warning symptoms
- Acute kidney injury and hyperkalaemia
- Anaphylaxis and serious skin reactions
- Hepatotoxicity: fulminant hepatitis, necrosis and liver failure, mostly in the first months

## Contraindications

- Hypersensitivity to the drug
- Asthma, urticaria or another allergic reaction after acetylsalicylic acid or another NSAID
- The setting of coronary artery bypass graft (CABG) surgery

## Key interactions

**Voriconazole and other CYP2C9 inhibitors**
Increase exposure to diclofenac.

**Anticoagulants (warfarin), antiplatelet agents, SSRIs and SNRIs**
Add to the risk of bleeding.

**ACE inhibitors, ARBs and diuretics**
Blunt their antihypertensive and diuretic effect; in older or volume-depleted patients they can precipitate acute kidney injury.

**Lithium**
Raise its blood levels by lowering renal clearance.

**Digoxin**
May raise its concentration and prolong its half-life.

## What is monitored

- Liver enzymes in long-term use
- Kidney function and potassium
- Blood pressure and oedema
- Signs of gastrointestinal bleeding

## Administration and safety

- Different diclofenac products (sodium, potassium, delayed-release) release the drug differently and are not interchangeable.
- Topical forms also exist; check that the patient is not receiving diclofenac by another route or another NSAID at the same time.

## Nursing care

- Before starting: history of ulcer, bleeding, kidney or cardiovascular disease, or asthma with NSAIDs.
- Watch for black stools, vomiting blood, abdominal pain and signs of anaemia.
- Watch blood pressure, oedema, urine output and creatinine, above all in older patients or those on diuretics.
- Teach the signs of liver injury: nausea, fatigue, itching, jaundice, dark urine and right upper abdominal pain.

## Pregnancy and breastfeeding

From about week 20 it can cause fetal kidney dysfunction with oligohydramnios, and from about week 30 premature closure of the ductus arteriosus; so use is limited between those weeks and avoided late in pregnancy.

## Memory aid

DICLOfenac = «a Disguised CLOne of the coxibs»: almost as COX-2 selective as celecoxib, with its thrombotic risk, and watch the liver too.

## Test yourself

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

## Why does diclofenac carry a cardiovascular risk similar to the coxibs?

Because its COX-2 selectivity resembles celecoxib's: it lowers vascular prostacyclin without fully blocking platelet thromboxane.

## Which adverse effect of diclofenac calls for monitoring liver enzymes?

Hepatotoxicity, which usually appears in the first months and can progress to fulminant hepatitis or liver failure.

## Which enzyme mainly metabolises diclofenac?

CYP2C9; its inhibitors, such as voriconazole, increase exposure to the drug.

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

## Related drugs

- [Celecoxib](https://durgical.com/en/pharmacology/celecoxib/)
- [Ibuprofen](https://durgical.com/en/pharmacology/ibuprofen/)
- [Naproxen](https://durgical.com/en/pharmacology/naproxen/)

## Related conditions

- [Knee Osteoarthritis](https://durgical.com/en/conditions/knee-osteoarthritis/)
- [Rheumatoid arthritis](https://durgical.com/en/conditions/rheumatoid-arthritis/)
- [Ankylosing spondylitis](https://durgical.com/en/conditions/ankylosing-spondylitis/)

[← Back to the class: Nonsteroidal anti-inflammatory drugs (NSAIDs)](https://durgical.com/en/pharmacology/classes/nonsteroidal-anti-inflammatory-drugs/)

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

Sources: [Diclofenac: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a689002.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [DICLOFENAC SODIUM tablet, delayed release](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0e5c6669-390f-4c32-b9b8-13ed3c517462) (DailyMed (U.S. National Library of Medicine), 2026); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 42 (McGraw Hill, 2023); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=M01AB05) (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/diclofenac/