The U.S. Food and Drug Administration (FDA) announced on May 16, 2025, that it will add warnings to prescription information for cetirizine (Zyrtec) and levocetirizine (Xyzal) regarding the risk of severe pruritus following discontinuation after long-term use. The agency is also requesting manufacturers add similar warnings to over-the-counter (OTC) versions of these popular antihistamines.
The FDA's decision follows the identification of 209 global cases of severe itching after stopping these medications between April 2017 and July 2023. The vast majority (197) of these cases occurred in the United States.
Rare but Serious Reaction Pattern Identified
According to the FDA's safety review, the itching typically occurs within days of discontinuing the medications after daily use for at least several months, though often after years of continuous treatment. Notably, affected patients did not experience pruritus before starting these antihistamines.
While the exact mechanism remains unknown, the FDA believes there is a causal link between stopping cetirizine or levocetirizine and the onset of pruritus. The agency noted that in some cases, the itching was severe enough to require medical intervention.
"Although reports of pruritus were rare, some patients experienced serious cases requiring medical intervention," the FDA stated in its announcement. The agency further advised that symptoms may improve upon restarting the medication, suggesting a potential rebound mechanism.
Widespread Use Amplifies Concern
The warning takes on particular significance given the widespread use of these medications. Cetirizine and levocetirizine are approved to treat seasonal allergic rhinitis in children aged 2 years and older and adults. They are also indicated for perennial allergic rhinitis and chronic idiopathic urticaria in patients as young as 6 months.
Most of these antihistamines are available over the counter, with more than 60 million purchases reported in 2022 alone. According to market research firm Numerator, nearly two-thirds (64%) of U.S. households purchased OTC allergic rhinitis medications between May 2023 and May 2024.
Guidance for Healthcare Providers
The FDA is advising healthcare professionals to inform patients about this potential risk, particularly when prescribing or recommending these medications for chronic use. Clinicians should explain that itching typically occurs within a few days of stopping these medications after daily use for extended periods.
"Encourage patients to contact you if they experience severe itching after stopping cetirizine or levocetirizine," the FDA advised healthcare providers. The agency also recommended discussing the benefits and risks of these medications before initiating treatment.
Patient Considerations
For patients currently taking these medications, the FDA is not recommending discontinuation unless advised by a healthcare provider. However, patients should be aware of this potential side effect if they plan to stop using the medication.
The updated labeling will indicate that pruritus symptoms may improve with restarting the medications, which could provide temporary relief while developing a longer-term discontinuation strategy with medical supervision.
Timing and Onset of Symptoms
Patients commonly reported experiencing pruritus after discontinuing the medications following three months of use, though some cases occurred after just one month of daily use. The itching can be widespread and, in some cases, severe enough to significantly impact quality of life.
This new safety warning highlights the importance of monitoring for unexpected effects even with commonly used and generally well-tolerated medications, particularly when used chronically or discontinued after extended periods.
