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Structural formula
Structural formula of diclofenac
Non-proprietary name Diclofenac
other names
  • 2- {2 - [(2,6-dichlorophenyl) amino] phenyl} ethanoic acid ( IUPAC )
  • 2- {2 - [(2,6-dichlorophenyl) amino] phenyl} acetic acid
Molecular formula
External identifiers / databases
CAS number
  • 15307-86-5
  • 15307-79-6 (diclofenac sodium salt)
  • 15307-81-0 (diclofenac potassium salt)
EC number 239-348-5
ECHA InfoCard 100,035,755
PubChem 3033
ChemSpider 2925
DrugBank DB00586
Wikidata Q244408
Drug information
ATC code
Drug class

Non-steroidal anti-inflammatory drug

Mechanism of action

Cyclooxygenase - inhibitor

Molar mass
  • 296.15 g · mol -1
  • 318.1 g · mol -1 (diclofenac sodium salt)
  • 334.2 g · mol -1 (diclofenac potassium salt)
Melting point

approx. 280 ° C (diclofenac sodium salt / decomposition)

pK s value



practically insoluble in water (2.37 mg l −1 at 25 ° C)

safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances
06 - Toxic or very toxic


H and P phrases H: 301
P: 301 + 310
Toxicological data

62.5 mg kg −1 ( LD 50ratoral )

As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Diclofenac (name derived from the English chemical name 2- [2- (2,6- Dic h lo rophenylamino) phen yl] ac etic acid ) is a drug selected from the group of non-opioid analgesics , of mild to moderate pain and inflammation is used, for example, for rheumatism , bruises , strains , lumbago , arthrosis , arthritis and sweat gland abscesses . Its effect is based on a nonselective inhibition of cyclooxygenases (COX), which form the inflammatory mediators , the prostaglandins , in the body . Chemically it belongs to the phenylacetic acids . In drugs, diclofenac is used in the form of various salts, e.g. B. as the sodium salt or diethylammonium salt .


Alfred Sallmann and Rudolph Pfister synthesized various substituted 2- (phenylamino) phenylacetic acids, including 2- {2 - [(2,6-dichlorophenyl) amino] phenyl} acetic acid , at the Swiss company JR Geigy AG in the 1960s . The compounds have been protected by patents as active ingredients against rheumatism and arthritis. Instead of the decarboxylation of N - (2,6-dichlorophenyl) anthranilic acid, a reduction with lithium alanate and chain extension using cyanide is also described. The synthesis of diclofenac is now carried out using a much simpler process via 2,6-dichlorodiphenylamine (CAS No. 15307-93-4) from 2,6-dichlorophenol via a Smiles rearrangement with subsequent Stollé reaction with chloroacetyl chloride (see reaction scheme ). Nine years later, this entire process was registered again by an Indian company using a phenoxyacetic ester. Parts of the process patent, the Smiles rearrangement, were claimed by Chinese authors four years after the initial filing.

major synthetic routes for diclofenac


Diclofenac has a fever-reducing ( antipyretic ), analgesic ( analgesic ), anti-inflammatory ( antiphlogistic ) and anti-rheumatic effect. The reason for this is an inhibition of the cyclooxygenases COX-1 and COX-2 , which are no longer able to produce inflammatory prostaglandins . Diclofenac may be directly involved in lipoxygenase metabolism and suppress the formation of leukotrienes . The analgesic effect of diclofenac is increased by piperine , an ingredient in pepper. The reason for this is possibly an increased bioavailability .


The most common use of Diclofenac is for pain or inflammation associated with injuries or diseases of the musculoskeletal system. In this area in particular, pain caused by injuries or inflammation often cannot be clearly differentiated from one another. Possible areas of application for Diclofenac are acute joint inflammation including gout attacks , chronic inflammation of the joints or painful swellings or inflammations after injuries or operations. In addition, Diclofenac is used for inflammatory forms of rheumatism and soft tissue rheumatism. It is also sold as a "pain gel" (for pain, inflammation and rheumatism).

As a gel (trade name Solaraze ), Diclofenac is used to treat actinic keratosis .

Side effects

Typical side effects are stomach and intestinal complaints caused by an inhibition of COX-1, which occurs in the gastric mucosa, among other things. In addition, blood formation disorders and hypersensitivity reactions can occur, such as hypersensitivity of the skin to sunlight. In addition, there may be strong increases in liver values ​​(for example transaminases ). As dizziness and fatigue can occur, caution should be exercised when operating machines and participating in road traffic. When used as a topical drug for the treatment of tendinitis ( tennis elbow ), allergic reactions due to reddening of the skin with pain formation can occur. In individual cases the function of the kidneys is impaired ( nephrotoxicity , analgesic nephropathy , uremia toxin ). Diclofenac rarely causes hives , and very rarely does hair loss occur. Heart attacks are very rare. In the United States, according to a ruling by the US Food and Drug Administration , the product information for preparations to be used on the skin must indicate that systemic side effects can occur.

In very rare cases, diclofenac has an acute relapsing effect in inflammatory bowel diseases ( Crohn's disease , ulcerative colitis ). In people with histamine intolerance , the allergen-specific histamine release can be increased in allergy sufferers.

In 2018 a cohort study from Denmark showed :

  • The risk of upper gastrointestinal bleeding after 30 days with diclofenac was similar to that with naproxen, but significantly higher than with no NSAID administration, paracetamol and ibuprofen.

In dogs treated with diclofenac, there are more gastrointestinal side effects compared to treatment with other nonsteroidal anti-inflammatory drugs (NSAID) approved for dogs .


Using other nonsteroidal anti-inflammatory drugs - such as acetylsalicylic acid or ibuprofen - or taking them with glucocorticoids increases the risk of gastrointestinal side effects. There are also interactions with lithium , phenytoin and cardiac glycosides , the serum levels of which are increased by diclofenac. Since these are substances with a narrow therapeutic range , overdoses can occur. Diclofenac can weaken the effects of medicines used to reduce water and blood pressure .

So far, no interactions between anti-coagulant substances such as phenprocoumon and diclofenac have been found in clinical studies , but it is recommended that the coagulation status be monitored closely when used at the same time .

Contraindications and restrictions on use

A contraindication to the use of diclofenac exists if there is hypersensitivity to the active substance or if reactions such as bronchospasm , asthma or nettle rash have become known after taking other non-steroidal anti-inflammatory drugs (NSAP) or acetylsalicylic acid in the past . In addition, diclofenac should not be taken before major surgery, as it increases the risk of bleeding. Diclofenac must not be used in the last trimester (3 months) of pregnancy.

There are insufficient studies of the use of diclofenac in children and adolescents, so it is not recommended for patients under 15 years of age.

Since 2005, various studies and meta-studies have been published which have shown an increase in the risk of a life-threatening heart attack by a factor of 1.55 after taking diclofenac. In 2012, the European Medicines Agency (EMA) completed its reassessment of the cardiovascular risk profile of NSAIDs. Thereafter, diclofenac was shown to have a slightly increased risk of cardiovascular events. As a result, the Pharmacovigilance Committee developed new instructions for use for systemically administered diclofenac-containing drugs, according to which high-risk patients ( heart failure of NYHA stages II to IV, ischemic heart disease , peripheral artery disease or a disease of the cerebral vessels ) should not take diclofenac and have significant risk factors for cardiovascular diseases the indication must be given special consideration. The risk of arterial thrombotic events was classified as comparable to that of the COX-2 inhibitors . In Australia, too, the state drug safety authority TGA ( Therapeutic Goods Administration ) issued warning notices regarding cardiovascular risks in April 2015 after a safety review.

Use in veterinary medicine

Use in dogs and cats can cause massive gastrointestinal damage, sometimes fatal. The damage caused by administration of this drug is one of the most common iatrogenic emergencies in dogs.

The EU maximum residue level regulation for food of animal origin allows the use of diclofenac in cattle and pigs, whereby maximum residue levels are set for the food obtained.


For the reliable qualitative and quantitative determination of Diclofenac in a wide variety of test materials such as B. water and wastewater samples or fish plasma, the coupling processes between HPLC , gas chromatography and mass spectrometry are used after suitable sample preparation .

Impact on the environment

70 percent of the diclofenac ingested by humans is excreted unchanged by the body in the urine. Since around 90 tonnes of the active ingredient are consumed in Germany every year, around 63 tonnes of diclofenac reach the surface waters and thus into the water cycle via the sewage treatment plants , where only part of the diclofenac is broken down. As part of a study from 2008, diclofenac concentrations in the one to three-digit nanogram per liter range were measured in European rivers. In 2019, diclofenac was detected in all 40 examined rivers in Austria (0.00042 - 1.1 μg / l). Toxicity studies have shown harmful effects on the liver and kidneys of certain fish species. For trout z. B., even half a microgram of diclofenac per liter of water leads to kidney damage.

The treatment of cattle with diclofenac in India, for example, unexpectedly led to a drastic decline in vulture populations in the 1990s and made protective measures necessary for the animals. The birds ingested the active ingredient through the pet carcasses. The affected vultures showed symptoms similar to gout at first, until they died of kidney failure . Use in veterinary medicine has been banned in India since March 2005. Following the approval of diclofenac for veterinary medicine in the EU in 2014, warnings of similar consequences have been issued in Spain, which is home to the largest vulture populations in Europe. Meloxicam , which is non-toxic for vultures, can be used instead of diclofenac .

Due to this increased environmental relevance, Diclofenac is one of the so-called "Chemicals of Emerging Concern" (CECs), ie substances that can potentially have a significant impact on humans and the environment, and has been included in the EU's "Watch List" of substances to be monitored with priority. The Predicted No Effect Concentration (PNEC) for diclofenac is 0.05 µg / l. In Germany, the diclofenac concentration was analyzed at 24 measuring points in surface waters in 2016. The PNEC was exceeded at 21 of the 24 measuring points (annual average).

Due to the environmentally harmful properties and the low benefit of diclofenac preparations (creams, gels) that are to be applied to the skin, the Swedish Medicines Commission advised against their use in 2019. Only a little of the active ingredient is absorbed at all, but the majority is washed off

Sales accrual

In Germany, drugs containing diclofenac require a prescription ; Exceptions are formulations with a diclofenac concentration of up to 5 percent for application on the skin, plasters for external use without further addition of pharmaceutically active ingredients in an amount of active ingredient of up to 140 mg per divided dosage form, and peroral dosage forms in single doses of up to 25 mg per divided form and a daily dose of up to 75 mg for lowering fever (for a maximum duration of use of three days) and for pain relief (for a maximum duration of use of four days).

In Austria, drugs containing diclofenac require a prescription, except for external use against pain and swelling after blunt injuries, muscle tension and lumbago.

Commercial preparations

The original preparation of the Geigy company is called Voltaren (D, A, CH). Other drug names are Agilomed (A), Algefit (A), Allvoran (D), Arthrex (D), Dedolor (A), Deflamat (A), Deflamm (A), Diclac (D), Diclo (D), Difene ( A), Difen-Stulln (D, CH), Dolostrip (A), Dolpasse (A), Ecofenac (CH), Effekton (D), Effigel (CH), Fenisole (CH), Flam-X (CH), Flector (D, CH), Fortenac (CH), Inflamac (CH), Jutafenac (D), Monoflam (D), Olfen (CH), Pennsaid (A), Primofenac (CH), Relowa (CH), Rewodina (D) , Sandoz pain gel (D), Solaraze (D, A), Tonopan (CH), Tratul (A), Vifenac (CH), Voltadol (A), Voltfast (CH), numerous generic drugs (D, A, CH)
Combination preparations
Arthrotec (D, A, CH), Combaren (D), Voltaren Plus (D), Dolo-Neurobion (A), Flectoparin (CH), Neodolpasse (A), Neurofenac (A), Olfen (CH), Tobrafen (CH ), Voltamicin (CH), numerous generics (D, A, CH)

Web links

Commons : Diclofenac  - collection of images, videos and audio files

Individual evidence

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