Guiding Patients Through Allergy Medication Safety: Pharmacists’ Role Following FDA Warning on Cetirizine and Levocetirizine

Amid peak allergy season, the FDA has issued a safety communication regarding 2 of the most commonly used allergy medications: cetirizine (Zyrtec; Kenvue) and levocetirizine (Xyzal; Opella).¹ These second-generation antihistamines are widely used to manage seasonal and perennial allergy symptoms, including sneezing, runny nose, and watery eyes.² In 2022 alone, an estimated 26.8 million prescriptions were filled and 62.7 million OTC packages were sold, highlighting their widespread use among millions of Americans.¹

Man taking allergy medication | Image credit: Andrey Popov | stock.adobe.com

These medications are available in both prescription and OTC formulations. Many patients prefer second-generation antihistamines for their effectiveness and favorable safety profile compared to first-generation antihistamines. However, in May 2025, the FDA issued a safety communication highlighting reports of rare but severe pruritus that may develop after discontinuing long-term use of cetirizine or levocetirizine.¹ The new safety concern may cause concern for individuals who take these medications chronically for daily relief. Pharmacists have a pivotal role in promoting safe medication use and helping patients understand the implications of regulatory updates. Pharmacists should provide education to patients on the appropriate use and duration of antihistamine therapy, counseling on the potential for withdrawal-related pruritus, and advice on strategies for tapering antihistamines when necessary.

Cetirizine and Levocetirizine

Cetirizine is an oral selective H₁-receptor antagonist available as a prescription in 5- and 10-mg strengths and is also available OTC in a 10-mg strength.³ It is available in both tablet and oral solution formulations and is approved for use in children as young as 6 months for specific indications with age-appropriate dosing.³ Levocetirizine is the active (R)-enantiomer of cetirizine, providing more potent and selective H₁-receptor antagonism.⁴ It is available by prescription and OTC, typically in a 5-mg strength for adults and children over 12. It can also be used in children 6 to 11 years with an adjusted recommended dose of 2.5 mg.⁴ Both medications are indicated for symptom management of seasonal allergic rhinitis, perennial allergic rhinitis, and treatment of uncomplicated chronic urticaria.^3,4 They are generally well-tolerated, with adverse effects including somnolence, dry mouth, and fatigue.^3,4 Their rapid onset of action within 1 hour and 24-hour duration make them a convenient once-daily option for allergy management.^3,4

Details of the FDA Warning

The FDA issued a warning after identifying 209 global cases (197 in the United States) of pruritus occurring after discontinuing cetirizine or levocetirizine between April 2017 and July 2023. The majority of cases involved cetirizine (n=180), followed by levocetirizine (n=27), and 2 cases involved both agents. Although this adverse effect appears to be rare and its underlying mechanism is still unknown, the FDA’s evaluation supports a relationship between abrupt discontinuation and the onset of pruritus. In most cases, symptoms developed after discontinuing therapy following more than 3 months of daily use, though some patients developed symptoms after less than 1 month. Notably, symptoms resolved after restarting the medication for most individuals, and a gradual taper after restarting also alleviated pruritus in some cases.¹

Significance and Next Steps

The significance of this adverse effect lies in its severity and the impact on quality of life. Many individuals reported widespread, persistent itching that required medical intervention and substantially affected their ability to function. Given the widespread use of these medications, the potential impact is substantial despite the rarity of the reaction. Besides the duration of medication use, the FDA has not identified any additional specific risk factors for this adverse effect.

The FDA will revise the prescribing information for both cetirizine and levocetirizine to include pruritus after discontinuation as a new warning. Additionally, the FDA is requesting that manufacturers update the Drug Facts label on OTC products to reflect this warning. The agency will also continue to monitor for additional reports of similar cases through the FDA Adverse Event Reporting System.¹

The Role of Pharmacists in Patient Safety and Counseling

Pharmacists, especially in ambulatory and community settings, are optimally positioned to address this emerging safety concern. Through medication reviews, counseling encounters, and OTC interactions, pharmacists can identify patients who may be at risk and provide anticipatory guidance on potential withdrawal symptoms.⁵

Key counseling considerations may include¹:

• Proactively initiating conversations with patients purchasing OTC formulations or picking up prescriptions about the potential adverse effects
• Discussing the potential for pruritus following discontinuation, particularly after extended use
• Reassuring patients that the adverse effect is rare and was only reported with cetirizine and levocetirizine, with no known risk factors
• Offering guidance on safe discontinuation strategies, including tapering the medications when appropriate
• Encouraging open communication between the patients and their providers on the benefit-risk ratio of long-term antihistamine use
• Helping patients recognize signs of severe or persistent pruritus
• Reinforcing the importance of reporting adverse effects through the FDA MedWatch program

Pharmacists should incorporate knowledge of this adverse effect in their clinical decision-making when recommending antihistamine therapy and consider additional monitoring for patients requiring long-term use.

Conclusion

The recent FDA communication underscores the importance of staying informed about emerging medication safety concerns. As highly accessible health care professionals, pharmacists play a significant role in educating patients, supporting therapeutic decision-making, and mitigating risks. Pharmacists help patients navigate safety updates and promote safe, informed medication use. Ongoing vigilance is essential for promoting optimal health outcomes and maintaining trust between patients and the health care system.

References

1. FDA requires warning about rare but severe itching after stopping long-term use of oral allergy medicines cetirizine or levocetirizine (Zyrtec, Xyzal, and other trade names). News release. FDA. May 16, 2025. Accessed July 8, 2025. https://www.fda.gov/drugs/drug-safety-and-availability/fda-requires-warning-about-rare-severe-itching-after-stopping-long-term-use-oral-allergy-medicines

2. May J. Allergic rhinitis. In: DiPiro JT, Yee GC, Haines ST, Nolin TD, Ellingrod VL, Posey L, eds. DiPiro’s Pharmacotherapy: A Pathophysiologic Approach. 12th ed. McGraw Hill; 2023.

3. Zyrtec [prescribing information]. Pfizer; 2002. Accessed June 16, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/19835s15,%2020346s8lbl.pdf

4. Xyzal [prescribing information]. UCB; 2008. Accessed June 16, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022064s009lbl.pdf

5. Ortega M, Isom C, Place A, et al. ASHP Statement on the Community Pharmacist’s Role in the Care Continuum. Am J Health Syst Pharm. 2024;82(1):96-102. doi:10.1093/ajhp/zxae176