U.S. FDA Drug Safety Alert: Warning Issued for Severe Itching After Stopping Long-Term Cetirizine or Levocetirizine Use

The U.S. Food and Drug Administration (FDA) has recently issued a warning that patients stopping the oral antihistamines - cetirizine or levocetirizine after long-term use may experience severe itching (pruritus).

The U.S. FDA drug safety communication released in the month of May 2025 stated, “Pruritus has been reported in individuals who used these medications daily, typically for several months and often for years. Although rare, some cases have been severe, involving widespread and intense itching that required medical intervention.” In response to the side effects, the U.S. FDA is updating the prescribing information for cetirizine and levocetirizine to include a warning about this potential risk as well as has asked the manufacturer to add a warning about pruritus in their Drug Fact Label

“Patients did not experience itching before starting the medicines,” the U.S. FDA’s drug safety alert further added. “The mechanism remains unclear, and aside from prolonged use, no specific patient characteristics or predisposing factors have been conclusively identified,” the communication further added

This advisory applies to prescription and over-the-counter (OTC) formulations of cetirizine and levocetirizine. Cetirizine was approved for oral use by prescription in December 1995, while levocetirizine was approved for prescription use in May 2007 and later for OTC use in January 2017. The two drugs are commonly used for treating seasonal allergic rhinitis, perennial allergic rhinitis, and chronic idiopathic urticaria.

Background and Data Leading to the FDA Decision:

Between April 25, 2017, and July 6, 2023, the FDA identified 209 reports of post-discontinuation pruritus, through the FDA Adverse Event Reporting System database. This included cetirizine 180 cases, levocetirizine 27 cases, and both in 2 cases.

The median time to onset was 2 days post-discontinuation (range: 1–5 days).

• In 92% of the 106 cases where usage duration was known, patients had used the medicine for more than 3 months.
• The median duration of use before symptom onset was 33 months (range: 1 week to 23 years).
• Many reports described widespread pruritus that adversely impacted quality of life and interfered with daily functioning.
• Serious outcomes included 48 cases of disability (such as debilitating itching to the point of being bed-ridden), 3 hospitalizations, and 2 reports involving thoughts of suicidal ideation or self-harm.

A causal association between stopping these medicines and subsequent pruritus was supported by repeated rechallenge data:

• In 93 cases where patients attempted restarting and stopping again, pruritus recurred in 92.
• Symptom resolution couldn’t be achieved in 10% of those who restarted therapy and in 62% of those who tapered the dose after restart.

Findings from Published Case Series

A case series by Chung et al. reviewed 146 cases of pruritus following cetirizine discontinuation reported to FAERS and medical literature. The median duration of prior use was 24 months, with symptoms typically beginning within 2 days of stopping the drug. Among those who discontinued twice, 98% experienced recurrence of pruritus. Restarting cetirizine relieved symptoms in 65%. [Chung et al., 2019].

Similarly, another case series from the Netherlands Pharmacovigilance Centre Lareb described 12 cases pruritus (defined as unbearable) occurring 1–3 days after stopping long-term cetirizine or levocetirizine. Most had failed multiple withdrawal attempts due to symptom severity. Gradual tapering helped in some cases [Ekhart et al., 2016].

The U.S. FDA’s warning reminded physicians to assess the benefit-risk profile of cetirizine and levocetirizine during use and the potential adverse effects following discontinuation.

“Physicians and pharmacists should inform patients about the potential risk of pruritus following cessation of cetirizine or levocetirizine, especially when use is anticipated to be chronic. Patients should be encouraged to report any severe or persistent itching following discontinuation. While controlled data on pruritus management in this context are lacking, anecdotal evidence suggests that symptoms may resolve upon re-initiation of therapy, and in some cases, through a gradual tapering strategy after reintroducing the drug.” the drug safety communication further added.

References

U.S. Food and Drug Administration. FDA Drug Safety Communication: Rare But Severe Itching after Stopping Long-Term Use of Cetirizine or Levocetirizine (Zyrtec, Xyzal). 16 May 2025. www.fda.gov. Accessed 4 June 2025.

Chung AH, La Grenade L, Harinstein LM. Pruritus after discontinuation of cetirizine. Ther Adv Drug Saf. 2019;10:2042098619859996. Published 2019 Jul 5. doi:10.1177/2042098619859996

Ekhart, Corine et al. “Unbearable Pruritus After Withdrawal of (Levo)cetirizine.” Drug safety - case reports vol. 3,1 (2016): 16. doi:10.1007/s40800-016-0041-9