Diclofenac is a widely used Nonsteroidal Anti-Inflammatory Drug (NSAID), a type of medication used to treat pain, inflammation, and fever. It is a phenylacetic acid derivative and is available in various forms, including oral tablets, topical gels, and injections.
The drug was first synthesized in 1973 by the Swiss company Ciba-Geigy (now part of Novartis). The problem it was designed to solve was the need for a highly active NSAID with good tolerability, and its structure was rationally designed based on other NSAIDs to have specific chemical characteristics, such as a phenylacetic acid group and a phenyl ring with chlorine atoms.
Diclofenac works primarily by inhibiting the activity of cyclooxygenase (COX) enzymes, specifically COX-1 and COX-2. These enzymes are responsible for the biosynthesis of prostaglandins, which are lipid compounds that mediate inflammation, pain, and fever. By blocking the COX enzymes, diclofenac reduces prostaglandin synthesis, thereby alleviating these symptoms.
In the Indian context, diclofenac is critically connected to the catastrophic decline of the country's vulture populations, including the critically endangered Gyps species like the white-rumped vulture (Gyps bengalensis). When the drug was widely used to treat livestock for pain and inflammation, vultures that fed on the carcasses of treated cattle ingested the drug, which caused fatal kidney failure and visceral gout. This environmental crisis led the Government of India to ban the veterinary use of diclofenac in 2006.
The regulation of diclofenac has changed significantly in India since the initial ban. Because multi-dose vials of diclofenac for human use were being illegally diverted for veterinary purposes, the Ministry of Health and Family Welfare issued a Gazette notification on July 17, 2015, restricting the packaging of diclofenac for human use to single-dose vials only. This was a crucial step to prevent the misuse of the drug, which continued to threaten the vultures. The ban on veterinary use remains, and the government has promoted the use of alternative NSAIDs, such as meloxicam, which is safe for vultures. Furthermore, in 2023, the government also banned other veterinary drugs, aceclofenac and ketoprofen, because they metabolize into diclofenac and are also toxic to vultures.