Have you ever had a sudden, relentless itch soon after you stopped taking your daily allergy medication? In mid-May, the U.S. Food and Drug Administration (FDA) issued a surprising warning- individuals who stop taking long-term usual over-the-counter antihistamines such as Zyrtec (cetirizine) or Xyzal (levocetirizine) may develop a severe, generalized itching a condition medically referred to as pruritus. Although uncommon, this reaction can be severe enough to seek medical attention, and it is an indication of how important it is to be educated prior to discontinuing these popular drugs.Tens of millions of Americans use cetirizine or levocetirizine every year to manage seasonal sneezes or chronic hives. In 2022 alone, over 62.7 million OTC units of these antihistamines were sold, and another 26.8 million were prescribed by outpatient pharmacies. However, between April 2017 and July 2023, the FDA reported 209 worldwide cases of intense itching after sudden stopping of these drugs—180 for Zyrtec, 27 for Xyzal, and two each for both. There were 197 cases in the United States, though experts assume this could be a low estimate because not all reactions are reported to the authorities."For now, we want to inform the public of this risk," the FDA said on May 16, 2025, stressing that although pruritus upon discontinuation of these drugs is rare compared with their widespread use, the agency is revising labeling and requesting manufacturers to place a warning on OTC Drug Facts labels.What Is Pruritus?Pruritus is the medical term for itching and may result from many causes, from dry skin to systemic disease. The Cleveland Clinic states that pruritus results when nerve endings in the skin are stimulated excessively by inflammatory pathways, allergens, or neurological disease. What is interesting about the FDA warning is that patients who had the reaction had no history of itching prior to starting their antihistamine treatment and the symptom would usually appear within days of ceasing the drug after months or even years of daily intake."Once in a while, this occurs, and Opella maintains the safety of Xyzal when taken as instructed," an Opella spokesperson told PEOPLE magazine, emphasizing that millions of people get along fine with these medications. A representative for Zyrtec, contacted by phone, also confirmed the drug's decades-long track record for safety but had no further information regarding the FDA alert.Why Does Stopping Antihistamines Trigger Severe Itching?Scientists continue to explore the exact mechanism. One hypothesis is that chronic antihistamine use can desensitize the histamine receptors or affect nerve conduction pathways. When the drug is discontinued, the receptors might become hyperresponsive and unleash a trail of itch-inducing chemicals into the skin. Since histamine also helps regulate nerve and inflammation functions, sudden withdrawal can unleash a rebound effect much more severe than typical dryness or superficial irritation.Dr. Karen Liu, an independent dermatologist and not involved in the FDA review, says, "Antihistamines quiet histamine-induced inflammation. If you all of a sudden take that blockage away after extended use, the body's normal histamine reaction can spike, causing severe pruritus."Who Is at Risk and What to Do Next?Although the majority of patients who experienced pruritus were taking Zyrtec or Xyzal daily for a minimum of three months, some had symptoms only after a few weeks of usage. Due to this inconsistency, the FDA recommends anyone considering prolonged antihistamine therapy to have the benefits and risks reviewed with their physician. If you experience violent itching several days after stopping cetirizine or levocetirizine, call your doctor at once.No formal treatments for withdrawal-induced pruritus have been sanctioned. Yet patients say restarting the antihistamine usually takes care of symptoms, and some find that slowing down the dose instead of just quitting works for them. "Physicians should balance the advantages of continuing therapy against the risk of rebound scratching," suggests Dr. Liu. Any restart or taper plan should be orchestrated by a physician.Warning Amid Intensifying Allergy SeasonsExperts point out that allergy incidence is increasing, partly due to climate change, which lengthens pollen seasons and doubles airborne allergens. As increasing numbers of individuals become dependent on daily antihistamines for symptom management, knowing about infrequent but dangerous side effects becomes critical. The FDA's actions to revise prescribing labels and over-the-counter warnings in line with a new guidance reflect a balance between transparency and patient protection and not discouraging therapeutic use."Meanwhile, patients should be alert," the FDA said. "If more information becomes available, we will follow up." This changing advice reflects the subtleties of long-term drug use—especially with drugs once assumed to be harmless.For millions, Zyrtec and Xyzal provide invaluable relief from itching, sneezing, and congestion. Yet this new warning is a reminder that no medication is entirely free of risk, especially when discontinuing after extended use. Before beginning—or stopping—long-term antihistamine therapy, consider these steps:Ask your doctor how long you should remain on daily antihistamines based on your allergy severity and lifestyle.Be mindful of the risk for intense itching and the availability to taper instead of abruptly stopping.Inform health professionals immediately if you develop unexplained or severe itching when you stop your allergy medication.Check for new Drug Facts labels on OTC medications and examine prescribing labels on prescription forms.Though serious post-discontinuation pruritus is uncommon, vigilance equips patients and doctors alike to proceed with allergy treatment knowing what to expect. As manufacturers, regulatory agencies, and medical professionals work together to update safety information, individuals are enabled to make well-informed decisions—so relief from summer discomfort does not yield to an unwanted and unpleasant reaction.