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The US Food and Drug Administration (FDA) is warning that patients who stop taking cetirizine (Zyrtec) or levocetirizine (Xyzal) after long-term use may experience rare but severe itching.

The agency said in a drug safety communication that between 2017 and 2023, it had received reports of 209 cases worldwide (197 in the United States) of pruritus developing within a few days of stopping cetirizine (n = 180), levocetirizine (n = 27), or both (n = 2). Patients had used the medications daily for periods ranging from 1 week to as long as 23 years, the agency said.

According to the FDA, the number of pruritus cases increased with duration of use. The itching often affected individuals’ quality of life and ability to function. Serious adverse outcomes included disability, such as being bedridden (48 cases), hospitalization (3), and thoughts of suicide or self-harm (2). “The underlying mechanism for this risk is unknown, but our evaluation supports a causal relationship between stopping cetirizine or levocetirizine and pruritus,” said the agency.

Antihistamines are frequently used, with the FDA estimating that 26.8 million cetirizine and levocetirizine prescriptions were dispensed in the United States in 2022, with an additional 62.7 million over-the-counter (OTC) cetirizine and levocetirizine products bought by consumers at retail outlets. Thus, the itching “appears to be rare compared to how often the medicine is used,” said the agency.

Pruritus resolved for most people either by restarting the medication or tapering off after restarting, said the agency. The FDA will require manufacturers to add a warning to prescription and OTC labeling about the risk of itching and the potential to resolve it by restarting the medication.

The agency advised individuals planning on long-term use of either of the medications to “discuss the benefits and risks with your healthcare professional.”

Adam Friedman, MD, professor and chair of Dermatology at George Washington University School of Medicine and Health Sciences, Washington, DC, said the warning was “full of missing holes.”

The agency’s warning doesn’t specify the dose, what the medication was being used for, or if there were specific demographic features among those who had pruritus, Friedman told Medscape Medical News. “I really struggle with interpreting this data in a meaningful way,” he said.

He also wonders whether clinicians should be concerned about other antihistamines like loratadine or fexofenadine.

In addition, the mechanism for pruritus is a mystery, said Friedman. “If the agency is saying that people are using this who don’t have any primary skin disease, have no itching, and now they’re itching, I can’t reconcile why that would be,” he said.

Friedman said he’s concerned that the warning will scare patients away from antihistamines during the height of allergy season.

Cases Have Been Reported Previously

In 2016, researchers in the Netherlands reported 12 cases of intense itching described as “unbearable” pruritus after stopping levocetirizine. And in 2019, FDA staffers published an analysis of 146 cases of itching after cetirizine withdrawal in the FDA Adverse Event Reporting System database and medical literature.

In July 2024, The People’s Pharmacy said in a blog post that it had received hundreds of reports of “unbearable itching resulting from sudden discontinuation of the allergy drug cetirizine,” which it said it had discussed with the FDA. But, the group said, it never found any descriptions of a withdrawal syndrome when the drug was still prescription-only, and there was limited information on the OTC labeling.

Friedman reported having no relevant financial relationships.

Alicia Ault is a Saint Petersburg, Florida-based freelance journalist whose work has appeared in many health and science publications, including Smithsonian.com. You can find her on X @aliciaault and on Bluesky @aliciaault.bsky.social.