Diclofenac, sold under the brand name Voltaren among others, is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain and inflammatory diseases such as gout.
[9] It is also available as the fixed-dose combination diclofenac/misoprostol (Arthrotec) to help protect the stomach; however, proton pump inhibitors such as omeprazole are typically first-line since they are at least as effective as misoprostol, but with better tolerability.
[14][15][16] Common side effects include abdominal pain, gastrointestinal bleeding, nausea, dizziness, headache, and swelling.
[15] Diclofenac is used to treat pain related to arthritis, dysmenorrhea, rheumatic diseases and other inflammatory disorders,[9] kidney stones and gallstones.
[28] In October 2020, the US Food and Drug Administration (FDA) required the prescription label to be updated for all nonsteroidal anti-inflammatory medications to describe the risk of kidney problems in fetuses that result in low amniotic fluid.
[28] Following the identification of increased risks of heart attacks with the selective COX-2 inhibitor rofecoxib in 2004, attention has focused on all the other members of the nonsteroidal anti-inflammatory drug group, including diclofenac.
Research results are mixed, with a meta-analysis of papers and reports up to April 2006 suggesting a relative increased rate of heart disease of 1.63 compared to nonusers.
As of January 2015, the MHRA announced that diclofenac would be reclassified as a prescription-only medicine (POM) due to the risk of cardiovascular adverse events.
[32] A subsequent large study of 74,838 Danish users of nonsteroidal anti-inflammatory drugs or coxibs found no additional cardiovascular risk from diclofenac use.
[33] A very large study of 1,028,437 Danish users of various nonsteroidal anti-inflammatory drugs or coxibs found the "Use of the nonselective NSAID diclofenac and the selective cyclooxygenase-2 inhibitor rofecoxib was associated with an increased risk of cardiovascular death (odds ratio, 1.91; 95% confidence interval, 1.62 to 2.42; and odds ratio, 1.66; 95% confidence interval, 1.06 to 2.59, respectively), with a dose-dependent increase in risk.
[43] Diclofenac has a relatively high lipid solubility, making it one of the few nonsteroidal anti-inflammatory drugs that are able to enter the brain by crossing the blood-brain barrier.
In practice, the use of some COX-2 inhibitors with their adverse effects has led to massive numbers of lawsuits alleging wrongful death by heart attack, yet other significantly COX-selective nonsteroidal anti-inflammatory drugs, such as diclofenac, have been well tolerated by most of the population.
[citation needed] Besides the COX-inhibition, several other molecular targets of diclofenac possibly contributing to its pain-relieving actions have recently been identified.
[59] In the United States, 1% diclofenac gel was approved by the FDA in 2007 as a prescription drug for the temporary relief of the pain of osteoarthritis of joints in the hands, knees, and feet.
The mechanism is presumed to be kidney failure;[66] however, toxicity may be due to direct inhibition of uric acid secretion in vultures.
At a meeting of the National Wildlife Board in March 2005, the Government of India announced it intended to phase out the veterinary use of diclofenac.
[76] "The loss of tens of millions of vultures over the last decade has had major ecological consequences across the Indian subcontinent that pose a potential threat to human health.
In many places, populations of feral dogs have increased sharply from the disappearance of Gyps vultures as the main scavenger of wild and domestic ungulate carcasses.
When the substance enters freshwater, it has an environmental impact and is considered more difficult to remove in wastewater treatment plants than, for example, ibuprofen.
In some species of birds, diclofenac causes accumulation of uric acid crystals in internal organs—especially the liver and kidneys—resulting in visceral gout, as well as cellular damage and necrosis.