Pharmacology · Nonsteroidal anti-inflammatory drugs (NSAIDs)

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)
Enzyme: Cyclooxygenase 2 (COX-2), also acting on COX-1
ATC code: M01AB05

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

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

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 →
Rheumatoid arthritis Rheumatoid arthritis →
Ankylosing spondylitis Ankylosing spondylitis →

Adverse effects

Common

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

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.

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)

← Back to the class: Nonsteroidal anti-inflammatory drugs (NSAIDs)

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 (MedlinePlus (U.S. National Library of Medicine), 2026); DICLOFENAC SODIUM tablet, delayed release (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 (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.