NSAIDs Marketed In US Will Have Stronger Label Warning About Risks During Late Pregnancy

In Drug Safety Communication, FDA says it is requiring labeling changes for Rx as well as OTC NSAIDs due to risk of rare but serious kidney problems in an unborn baby.

Manufacturers of OTC NSAIDs marketed in the US will be required to change labeling to more strongly warn against using the drugs during the last three months of pregnancy because the ingredients may cause problems in the unborn child or complications during delivery.

The Food and Drug Administration on 15 October announced in a Drug Safety Communication that it is requiring labeling changes for Rx as well as nonprescription nonsteroidal anti-inflammatory drugs due to the risk of rare but serious kidney problems in an unborn baby, which can lead to low levels of a woman’s amniotic fluid and the potential for pregnancy-related complications.

The FDA already requires OTC NSAID Drug Fact labels to include a warning to avoid using the products during the last three months of pregnancy because the medicines may cause problems in the unborn child or complications during delivery and a statement advising pregnant and breastfeeding women to ask a health care professional before using the drugs.

The requirement for a stronger warning is based on the FDA's review of medical literature and cases reported to it about low amniotic fluid levels or kidney problems in unborn babies associated with NSAID use during pregnancy.

NSAID ingredients available OTC in the US include aspirin, ibuprofen, naproxen and diclofenac, although the FDA’s requirement for label warnings doesn’t apply to low-dose aspirin, 81 mg. The agency noted low-dose aspirin may be needed by some pregnant women and should be taken under the direction of a health care professional. 

The FDA Center for Drug Evaluation and Research says OTC NSAIDs manufacturers will have 30 days to respond to the center with their plans for complying with the Drug Facts label changes notification. Each of those firms will be allowed “a period for discussion with the agency” to determine how its NSAID product DFls will be changed, a CDER representative told HBW Insight.

Similar to the agency and OTC manufacturers' discussions for previous DFl changes, CDER will discuss with NSAID marketers about how they will state stronger warnings about use during pregnancy and when they expect to make the changes.

Bayer Aspirin and other otc nsaids, other than low-dose (81 mg) aspirin, will change label warnings to more strongly advise avoiding use during the last three months of pregnancy.

The Consumer Healthcare Products Association noted the change adds a pregnancy-related warning to OTC NSAID DFls. “CHPA recognizes that FDA is strengthening the existing warning for pregnant women on the OTC Drug Facts Label for NSAIDs. Our members will work with FDA to update labels accordingly,” said the trade groups in a statement. 

For safety labeling changes to Rx NSAIDs, though, the FDA expects the process to be completed “as soon as possible.” The agency is requiring changes to NSAIDs prescribing information to describe the risk of kidney problems in unborn babies that result in low amniotic fluid and to recommend limiting NSAID use to between about 20 weeks to 30 weeks of pregnancy because of the risk.

Another NSAID DFl Change

NSAIDs are among the most commonly used OTCs and requiring a label warning about use during pregnancy will have numerous manufacturers making DFl changes for hundreds of products.

Aspirin, ibuprofen and naproxen are available OTC as oral products while diclofenac is available nonprescription only as a topical.

The products include reliable sales leaders for large pharma firms’ consumer health businesses such as ibuprofen brands Tylenol for Johnson & Johnson and Advil for GlaxoSmithKline plc and naproxen-containing Aleve for Bayer AG, which also makes the iconic Bayer Aspirin.

Diclofenac became available OTC for the first time in the US earlier in 2020 with the FDA’s approval of GSK’s supplemental new drug application for Voltaren Arthritis Pain containing a 1% concentration. The OTC switch didn’t come with market exclusivity and generic equivalents from multiple manufacturers already are available.  (Also see "OTC Switch Brands Voltaren, Pataday Are Fast On Their Feet Following US Approval To Drive Sales" - HBW Insight, 13 Oct, 2020.)

The DFl change is the second required for OTC NSAIDs in five years. In 2015, the FDA required that labels warn non-aspirin NDAIDs “cause an increased risk” of heart attack or stroke, a change from labeling of “may” cause a higher risk. (Also see "FDA Wants Stronger Cardiovascular Warning For OTC NSAIDs" - HBW Insight, 10 Jul, 2015.)

FDA said then that DFls labels on OTC non-aspirin NSAIDs already included information on heart attack and stroke risk, but it requested updates to the labels based on its review of information showing that non-aspirin NSAIDs increase the chance of a heart attack or stroke.

Changes to OTC NSAIDs labeling in response to the 2015 requirement still are being proposed and evaluated by CDER. (Also see "OTC Decisions In April: Naproxen CV Risk Warning, Sun US Line Rises, Perrigo Omeprazole 'Melt In Mouth' Flag" - HBW Insight, 6 May, 2020.)

As with the warning against use during pregnancy, the agency required stronger warnings about cardiovascular risks on prescription NSAIDS’ Drug Facts labels.