FDA Side Effect Update: NSAIDs and Life-Threatening Reactions

Welcome to the FDA Side Effects Update. This series is designed to keep you informed about the latest safety advisories and newly documented side effects of your NSAIDs medications.

How to Read This Report

This report is prepared using the most recent information posted in the SrLC database. It highlights recent safety labeling changes. It includes only newly reported side effects and safety information; additional side effects and warnings will appear on the drug label. Not all recent changes to the SrLC database or the label may be listed here. For all changes and the complete list of warnings and side effects, please click on the drug label link.

Each of the items (approval and update dates, drug names, etc.) contained in this report are obtained from the SrLC. The side effects and medication descriptions are simplified and made clearer, if needed. Sometimes, additional sources, like a medical dictionary, may be used to translate technical medical phrases. Other sources (company news, FDA press releases, etc.) may be used to learn about some label changes.

Side Effect Update for Prescription NSAIDs

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used pain medicines. Available both over-the-counter and in prescription-only formulations, NSAID medications are used to treat fever, muscle pain, arthritis pain, headaches, menstrual cramps, pain caused by injuries or surgery, and more.

NSAID medications may be taken as capsules, tablets, liquid, topical creams, and by I.V. or injection in a hospital setting.

In the fourth quarter of 2022, the FDA reported that it had received a number of NSAID-related adverse events reports for a serious skin reaction called “generalized bullous fixed drug eruption” and that it would “evaluate the need for regulatory action.” Fixed drug eruption is a serious skin rash or blistering reaction to a drug that usually occurs in the same location each time the person uses the medication.

In July 2024, the FDA began to notify NSAID manufacturers that labels should be updated to include warnings about fixed drug eruptions. The required updates only include prescription NSAIDs, not over-the-counter versions like Advil, Aleve, and Motrin. Over-the-counter NSAID labels include a general warning about potential skin reactions, but do not specify the risk of “fixed drug eruptions.”

Starting on November 21, 2024, more than 50 safety updates for prescription NSAIDs were filed with the FDA. Here are descriptions of the updates for some of the more commonly prescribed medications in the category. Please check the SRLC database to search for additional NSAID drugs.

Arthrotec (active ingredient: diclofenac sodium; misoprostol)

Initial FDA Approval: 1997

Side Effect Update Date: November 21, 2024

Medication Description: Treats osteoarthritis and rheumatoid arthritis in adult patients at high risk of developing NSAID-induced gastric and duodenal ulcers.

Updated Side Effects/Safety Information: Warns of the risk of a serious skin reaction called 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.

FDA Safety Announcement: Arthrotec FDA Safety Label Change and Revised Drug Label
The revised drug label contains a complete list of FDA-approved indications, side effects, warnings, and more.

Cambia (active ingredient: diclofenac potassium) powder

Initial FDA Approval: 1998

Side Effect Update Date: November 21, 2024

Medication Description: Treats attacks of migraine headaches in adults.

Updated Side Effects/Safety Information: Warns of the risk of a serious skin reaction called 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.

Essential Extras: Administered from a one-dose packet with powder that is mixed with water.

FDA Safety Announcement: Cambia FDA Safety Label Change  and Revised drug label
The revised drug label contains a complete list of FDA-approved indications, side effects, warnings, and more.

Celebrex (active ingredient: celexocib)

Initial FDA Approval: 1998

Side Effect Update Date: November 21, 2024

Medication Description: Treats osteoarthritis (OA), rheumatoid arthritis (RA), juvenile rheumatoid arthritis (JRA) ankylosing spondylitis, acute pain, menstrual cramps.

Updated Side Effects/Safety Information: Warns of the risk of a serious skin reaction called 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.

FDA Safety Announcement: Celebrex FDA Safety Label Change and Revised drug label
The revised drug label contains a complete list of FDA-approved indications, side effects, warnings, and more.

Daypro (active ingredient: oxaprozin) caplets

Initial FDA Approval: 1992

NSAIDs  Side Effect Update Date: November 21, 2024

Medication Description: Treats osteoarthritis (OA) and rheumatoid arthritis (RA)

Updated Side Effects/Safety Information: Warns of the risk of a serious skin reaction called 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.

FDA Safety Announcement: Daypro FDA Safety Label Change and Revised drug label
The revised drug label contains a complete list of FDA-approved indications, side effects, warnings, and more.

Duexis (active ingredient: famotidine; ibuprofen)

Initial FDA Approval: 2011

Side Effect Update Date: November 21, 2024

Medication Description: Treats osteoarthritis (OA) and rheumatoid arthritis (RA) while decreasing the risk of developing an ulcer from ibuprofen use.

Updated Side Effects/Safety Information: Warns of the risk of a serious skin reaction called 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.

FDA Safety Announcement: Duexis FDA Safety Label Change and Revised drug label
The revised drug label contains a complete list of FDA-approved indications, side effects, warnings, and more.

Feldene (active ingredient: piroxicam)

Initial FDA Approval: 1982

Side Effect Update Date: November 21, 2024

Medication Description: Treats osteoarthritis (OA) and rheumatoid arthritis (RA)

Updated NSAIDs Side Effects/Safety Information: Warns of the risk of a serious skin reaction called 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.

FDA Safety Announcement: Feldene FDA Safety Label Change and Revised drug label
The revised drug label contains a complete list of FDA-approved indications, side effects, warnings, and more.

Indocin (indomethacin) oral suspension and indomethacin (indomethacin) (various formulations)

Initial FDA Approval: 1985 (oral suspension formulation); 1965 (capsules)

Side Effect Update Date: November 21, 2024

Medication Description: Treats moderate to severe rheumatoid arthritis (RA) including acute flares; ankylosing spondylitis; osteoarthritis; acute painful shoulder; gouty arthritis

Updated Side Effects/Safety Information: Warns of the risk of a serious skin reaction called 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.

FDA Safety Announcement: Indocin Safety Label Change and Revised Drug Label

Indomethacin FDA Safety Label Change and Revised drug label
The revised drug label contains a complete list of FDA-approved indications, side effects, warnings, and more.

Meloxicam (active ingredient: meloxicam) oral suspension

Initial FDA Approval: 2004

Side Effect Update Date: November 21, 2024

Medication Description: Treats osteoarthritis (OA), rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA)

Updated Side Effects/Safety Information: Warns of the risk of a serious skin reaction called 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.

FDA Safety Announcement: Meloxicam FDA Safety Label Change and Revised Label
The revised drug label contains a complete list of FDA-approved indications, side effects, warnings, and more.

Naprosyn (naproxen) tablets and EC-NAPROSYN (naproxen) delayed release tablets, and ANAPROX DS (naproxen sodium) tablets

Initial FDA Approval:1976

Side Effect Update Date: November 21, 2024

NSAIDs Description: Treats moderate to severe rheumatoid arthritis (RA); ankylosing spondylitis; osteoarthritis; bursitis; gout; menstrual cramps; pain management.

Updated NSAIDs  Side Effects/Safety Information: Warns of the risk of a serious skin reaction called 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.

FDA Safety Announcement: Naprosyn FDA Safety Label Change and Revised Drug Label (covers all 3 versions of naproxen)
The revised drug label contains a complete list of FDA-approved indications, side effects, warnings, and more.

Zipsor (diclofenac potassium) tablets

Initial FDA Approval: 1988

Side Effect Update Date: November 21, 2024

NSAIDs Description: Treats mild to moderate acute (not chronic) pain in adults and children age 12 and up.

Updated Side Effects/Safety Information: Warns of the risk of a serious skin reaction called 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.

FDA Safety Announcement: Zipsor FDA Safety Label Change and Revised Drug Label
The revised drug label contains a complete list of FDA-approved indications, side effects, warnings, and more.

Essential Safety Extras for All NSAIDs Prescription Drugs:

All include a boxed warning for “serious cardiovascular and gastrointestinal events.”

FDA NSAIDs Safety Communication: FDA strengthens warning that non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) can cause heart attacks or strokes

In October 2020, the FDA released a safety communication stating that use of NSAIDs around 20 weeks or later in pregnancy may cause rare but serious kidney problems in an unborn baby. This can lead to low levels of amniotic fluid surrounding the baby and possible complications.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): Drug Safety Communication – Avoid Use of NSAIDs in Pregnancy at 20 Weeks or Later | FDA

FDA safety information page on NSAIDs: Nonsteroidal Anti-inflammatory Drugs (NSAIDs) | FDA