The U.S. Food and Drug Administration (FDA) has issued a safety alert for the popular antihistamines cetirizine (Zyrtec) and levocetirizine (Xyzal), warning that patients may experience severe itching (pruritus) after stopping long-term use of the drugs. This adverse effect has prompted updates to the drugs’ prescribing information for both prescription and over-the-counter (OTC) formats.

Key Highlights

Post-discontinuation pruritus observed

• Itching typically begins within 1–5 days of stopping the medication.

• Most cases involved cetirizine (86%), and 94% were reported in the U.S.

• Median duration of use before symptoms was 33 months, though some developed symptoms even after a month or less.

Adverse outcomes reported

• The FDA documented 209 global cases (April 2017–July 2023).

• Serious outcomes included:

  1. 48 cases of disability

  2. 3 hospitalizations

  3. 2 reports of suicidal thoughts or self-harm

• Pruritus was often widespread and distressing, significantly affecting quality of life.

Effectiveness of restarting or tapering

• 90% of individuals experienced relief after restarting the medication.

• Among those who attempted tapering after restarting, 38% saw complete resolution.

FDA recommendations for providers

• Clinicians should discuss this risk with patients, especially those prescribed these antihistamines for long-term use.

• Updated labels will include warnings about pruritus on discontinuation.

Drugs’ current indications and market reach

• Both drugs are approved for:

  1. Seasonal and perennial allergic rhinitis (age 6 months+)

  2. Chronic idiopathic urticaria

• Over 60 million OTC packs were sold in the U.S. in 2022 alone.

With widespread use of cetirizine and levocetirizine, the FDA’s safety alert brings critical attention to a lesser-known withdrawal side effect—post-discontinuation pruritus. Clinicians are advised to counsel patients and consider gradual tapering if long-term use is expected.