Ragweed season is underway, which means many Americans are about to finish a summer of daily antihistamines and simply stop taking them. For a small number of long-term users of two specific drugs, that is when a problem can begin.
Federal regulators require a warning on cetirizine, sold as Zyrtec, and levocetirizine, sold as Xyzal, about severe itching that can appear after stopping the medicine following months or years of daily use. The itching is not the allergy coming back. In the reported cases, it was widespread, sometimes severe enough to require medical care, and it occurred in people who had no itching before they started the drug.
This matters because of scale. The Food and Drug Administration estimated that in 2022 consumers bought about 62.7 million packages of the over-the-counter versions, and U.S. outpatient pharmacies dispensed about 26.8 million prescriptions for these two drugs. Even a rare reaction in a user base that size reaches a lot of households, and most of those households never speak to a pharmacist about the purchase.
The Reaction Regulators Found in 209 Reports
The FDA drug safety communication, issued in May 2025, describes 209 cases worldwide, 197 of them in the United States, identified in the agency's adverse event reporting database between April 25, 2017, and July 6, 2023. Cetirizine accounted for 180 of them, levocetirizine for 27, and both drugs for 2.
The pattern across those reports was consistent. People had been taking the medicine daily, typically for at least a few months and often for years. The median duration of use before the reaction was 33 months, with a range from one week to 23 years. They stopped. Itching began a median of two days later. Many reports described widespread itching that significantly affected quality of life and the ability to function, and reported outcomes included disability and, in a small number of cases, hospitalization.
Restarting the medicine resolved the itching in 71 of 79 people who tried it. Tapering off after restarting resolved symptoms in 9 of 24 who took that route.
Two limitations belong up front rather than buried. The agency has not established an incidence rate, so nobody can say what percentage of long-term users this affects. And because adverse event reports are voluntary, the true number of cases is unknown. Regulators describe the reaction as rare but sometimes serious, and note that their evaluation supports a causal relationship between stopping these two drugs and the itching.
The mechanism is not established. A clinical communication written by FDA staff and published in a peer-reviewed allergy journal describes one hypothesis: after long-term use, histamine H1 receptors are reduced to lower levels, and abruptly removing the drug that was occupying them may leave histamine with proportionately greater access. The authors write that this requires further investigation.
Reading the Fine Print on the Box
Prescription labeling for both drugs was revised to include the warning, and the agency asked manufacturers to add it to the Drug Facts label on the over-the-counter versions. That second step is the one that reaches ordinary shoppers, and it is now working through the system.
The FDA sent manufacturers formal supplement request letters in July 2025. Approval letters posted since then show the agency clearing revised Drug Facts labels carrying a warning about new-onset pruritus after discontinuation, including for over-the-counter cetirizine capsules and for Children's Xyzal oral solution.
The federal drug information pages for cetirizine and levocetirizine both now open with the warning, which is a reasonable place to check a medicine you have been taking without much thought.
Older boxes already in medicine cabinets will not carry the language. Neither will many store brand packages, since generic cetirizine is sold under dozens of retailer labels.
Reactions Reported for These Two Drugs, Not the Whole Shelf
The available evidence points to cetirizine and levocetirizine specifically rather than to antihistamines as a class. FDA staff have written that the agency has not received reports of comparable volume or quality for other H1 antihistamines. Both drugs are piperazine derivatives. Loratadine, sold as Claritin, and fexofenadine, sold as Allegra, have a different chemical structure, and the reaction has not been established for them.
Levocetirizine is chemically the mirror-image half of cetirizine, which is why the two behave similarly here.
That distinction is useful but should not be turned into a recommendation. Switching allergy medicines is a decision for a clinician or pharmacist who knows the rest of a person's medication list, not something to do based on a news article. Nobody taking these drugs should stop them because of this warning. Most reports came from people who had used the drug for more than three months, though a small number of cases followed less than a month of use.
Options Clinicians Have Tried
For someone who develops persistent widespread itching after stopping one of these medicines, the reported approaches have included restarting the antihistamine and tapering off slowly rather than stopping abruptly. The FDA notes that effective treatments for the reaction itself have not been formally evaluated.
None of that is a self-treatment protocol, and some patients in the reports needed medical intervention. Contact a clinician or pharmacist rather than experimenting.
Warning signs worth a call include itching that is widespread rather than localized, itching that starts within days of stopping a long-term antihistamine, itching severe enough to disrupt sleep or daily activity, and itching that persists beyond a week. Tell the clinician exactly how long the medicine was taken and when it was stopped, because that timeline is what distinguishes this reaction from a returning allergy or a new skin condition.
The FDA has said it will follow up as more information becomes available, and its safety information page for these medicines is where any update would appear first. Patients and clinicians can report reactions through the MedWatch program, which is the pipeline that produced these 209 cases in the first place.
Key Questions Answered
Which medicines are involved? Cetirizine, sold as Zyrtec and many store brands, and levocetirizine, sold as Xyzal. Both prescription and over-the-counter forms are covered.
Who is at risk? People who took one of these daily for at least a few months, and often years, and then stopped. Most reported cases involved more than three months of use.
How common is it? Unknown. Regulators identified 209 reports over roughly six years but have not established an incidence rate, and voluntary reporting means the real number is uncertain.
Should I stop taking my allergy medicine? No. Nothing in the warning suggests stopping. Talk with a clinician or pharmacist before changing any antihistamine.
Does this apply to Claritin or Allegra? The reaction has been reported for cetirizine and levocetirizine. Loratadine and fexofenadine have a different chemical structure, and the reaction has not been established for them.
What does the itching look like? Widespread rather than localized, beginning a median of two days after stopping, sometimes severe enough to disrupt sleep or require medical care. It was absent before the person started the medicine.
What should I do if it happens? Contact a clinician or pharmacist and tell them how long you took the medicine and when you stopped. Reported approaches include restarting or tapering, all under medical guidance.
