FDA issues warning regarding common antihistamines

The FDA warned that some people develop severe itching, or pruritus, after stopping long-term use of the antihistamines cetirizine (Zyrtec) or levocetirizine (Xyzal). Prescribing information for the oral allergy drugs — which are taken daily and sold both in prescription and over-the-counter (OTC) forms — will be updated to warn about the post-discontinuation risk. The itching typically occurs within a few days of stopping the products. “Restarting the medicine resolved pruritus in most individuals, and tapering off the medicine after restarting it resolved symptoms in some who tried this approach,” the FDA said in its safety communication.

A review of reports to the FDA Adverse Event Report System database showed rare but sometimes serious cases of pruritus(itching) that required medical intervention. From April 2017 to July 2023, there were 209 cases globally of pruritus after stopping cetirizine, levocetirizine, or both among individuals who did not experience itching before starting the drugs. Most cases (86%) involved cetirizine, and 94% were in the U.S. Some users experienced the severe itching after stopping the oral allergy drugs after less than 1 month of use, but 92% had been using the drugs for more than 3 months (median 33 months). Median time to pruritus onset was 2 days (range 1-5). Post-discontinuation pruritus was often widespread, affecting many areas of a user’s body, as well as quality of life, according to the reports. Infrequent serious outcomes were also reported, including disability (n=48), hospitalization (n=3), and thoughts of suicide/self-harm (n=2).

The FDA said that medical providers should discuss the risks of pruritus when recommending or prescribing cetirizine or levocetirizine to patients, especially if long-term use is anticipated. In 90% of cases, restarting cetirizine or levocetirizine resolved the pruritus. In 24 individuals who tried tapering off the products after restarting treatment, nine (38%) had their symptoms resolved. “The underlying mechanism for this risk is unknown, but our evaluation supports a causal relationship between stopping cetirizine or levocetirizine and pruritus,” the FDA stated. Beyond prolonged use, no other risk factors were identified. The two antihistamines are approved for seasonal allergic rhinitis in individuals 2 years and up, along with perennial allergic rhinitis and chronic idiopathic urticaria in those 6 months and older. Cetirizine has been available OTC since 2007 and levocetirizine since 2017. According to estimates, over 60 million packages of the two OTC drugs were sold at U.S. retail outlets in 2022.

Dr. Kenneth Backman of Allergy & Asthma Care comments: “We have long heard complaints of pruritus (itching) and hives from patients who have recently stopped cetirizine and levocetirizine, and have discussed this “withdrawal” phenomenon with our patients. It is not generally dangerous, but can be troubling. As noted above, restarting the antihistamine typically resolves the symptoms, and another option is to try switching to an alternative antihistamine, such as Allegra (fexofenadine) which appears to cause these symptoms much less often. Either way, this temporary, fairly infrequent phenomenon is not a reason to avoid these very safe and highly effective medications.”