Can Xyzal Cause Headaches?
Yes, headache is a recognized adverse effect of Xyzal (levocetirizine), though it occurs relatively infrequently compared to other antihistamines.
Evidence from Real-World Data
The most comprehensive safety data comes from FDA Adverse Event Reporting System (FAERS) analysis, which examined neurological adverse events across newer-generation antihistamines. Notably, fexofenadine showed the strongest association with headaches among the antihistamines studied, while levocetirizine was more prominently associated with somnolence rather than headache 1. This suggests that while headache can occur with levocetirizine, it is not the predominant neurological adverse effect of this medication.
Clinical Trial Safety Profile
In controlled clinical trials of levocetirizine for perennial allergic rhinitis, the adverse event profile was generally favorable. The medication demonstrated good tolerability with adverse events comparable to placebo in an 8-week study 2. In longer-term studies, the most commonly reported adverse events included headache, pharyngitis, influenza, fatigue, and somnolence, though specific incidence rates for headache alone were not isolated from other symptoms 3.
Comparative Context
When comparing levocetirizine to other second-generation antihistamines:
- Somnolence is the most frequently reported adverse event with levocetirizine, showing a reporting odds ratio of 28.5 (95% CI: 26.7-30.3), which is substantially higher than other antihistamines in this class 1
- Headache appears less prominently in the adverse event profile compared to sedative effects 1
- The overall tolerability profile remains acceptable, with most patients able to continue treatment 4, 3
Clinical Management Considerations
If headache develops while taking levocetirizine:
- Consider whether the headache is medication-related or due to the underlying allergic condition, as untreated allergic rhinitis itself can cause headache
- NSAIDs are recommended as first-line treatment for medication-induced headaches of moderate severity 5
- Avoid using acute headache treatments more than twice per week to prevent medication overuse headache 5
- Do not use opioids or butalbital-containing medications for chronic medication-related headaches due to dependency and rebound headache risks 5
- If headaches persist despite appropriate management, consult with the prescribing physician about alternative antihistamine options such as fexofenadine (though note it has higher headache association) or desloratadine 5, 1
Important Caveats
The sedative effects of levocetirizine warrant greater clinical concern than headache, as somnolence occurs more frequently and with stronger association 1. Patients should be counseled about this more common adverse effect when initiating therapy. The overall benefit-risk profile remains favorable for treating allergic rhinitis and chronic idiopathic urticaria, with levocetirizine demonstrating significant efficacy for symptom relief including the unexpected benefit of reducing nasal congestion 4, 2.