For those of you who follow the daily approvals page (here), on November 21, 2024, there was a flurry of supplemental labeling approvals listed for drug products that contain non-steroidal anti-inflammatory drugs (NSAIDs), from aspirin to Zipsor (diclofenac potassium). In today’s CDER Drug Safety-related Labeling Changes (SrLC), the new, revised warning that must be included was made more obvious; see example below for indomethacin (note underlined and bolded text):
NSAIDs, including indomethacin, can cause serious skin adverse reactions such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. NSAIDs can also cause fixed drug eruption (FDE). FDE may present as a more severe variant known as generalized bullous fixed drug eruption (GBFDE), which can be life-threatening. These serious events may occur without warning. Inform patients about the signs and symptoms of serious skin reactions, and to discontinue the use of indomethacin at the first appearance of skin rash or any other sign of hypersensitivity. Indomethacin is contraindicated in patients with previous serious skin reactions to NSAIDs.
While serious skin adverse reaction warnings have appeared in labeling for NSAIDs for years, this new warning is now becoming standard for inclusion for all products for which this Adverse Drug Event (ADE) is possible. No background on the changes to date was provided; however, I am certain that if your firm has an NSAID on the market, you likely received a letter asking that this revision be made.
One sources notes that “Fixed drug eruptions are linked to anti-infective (ß-lactam antibiotics, tinidazole, and acyclovir), analgesics (acetaminophen (paracetamol), mefenamic acid, and metamizole), non-steroidal anti-inflammatory drugs (NSAIDs), anti-epileptic (carbamazepine), psychoactive (barbiturates, codeine, and others), and other miscellaneous medications (omeprazole, contrast media, loratadine, and allopurinol)” (see here) and they can be very serious in nature. Based on this new warning and the potential for other drug classes to cause the same reaction, we are likely to see ADE warnings for other drug products be revised shortly.
