Xyzal (levocetirizine) is generally safe on its own, but it interacts poorly with alcohol, certain medications that increase its concentration in your blood, and several health conditions that change how your body processes it. Most of the concerns fall into a few clear categories: things that make you drowsier, things that slow the drug’s elimination, and conditions where the drug can build up to unsafe levels.
Alcohol and Sedating Substances
The most common interaction people run into is mixing Xyzal with alcohol. Xyzal already causes drowsiness on its own, and alcohol amplifies that effect. Together, they can worsen dizziness, poor concentration, unusual dreams, and trouble sleeping. This applies to any substance that slows down your central nervous system: sleep aids, anti-anxiety medications, muscle relaxants, opioid pain relievers, and other sedating antihistamines like diphenhydramine (Benadryl).
If you take Xyzal in the evening (which many people do, since drowsiness is its most common side effect), even a glass or two of wine can leave you noticeably more impaired than either would alone. This is especially relevant for driving or operating machinery the next morning.
Medications That Raise Xyzal Levels
Two specific drugs have been shown to change how your body clears Xyzal from your system:
- Ritonavir, an antiviral used in HIV treatment, increases the amount of the drug circulating in your blood by about 42%. It also makes the drug stick around roughly 53% longer by slowing its elimination. That combination means significantly more antihistamine effect, including more drowsiness and side effects.
- Theophylline, used for asthma and COPD, reduces Xyzal’s clearance by about 16% at standard doses. Higher theophylline doses could have a larger effect.
On the other hand, several commonly used drugs have been tested and show no meaningful interaction with Xyzal. These include pseudoephedrine (the decongestant often paired with antihistamines), azithromycin, erythromycin, ketoconazole, and cimetidine.
Kidney Problems
This is the most important safety concern with Xyzal. Your kidneys are responsible for clearing the drug from your body, so reduced kidney function causes it to accumulate. The worse your kidneys work, the more the drug builds up.
People with end-stage kidney disease or those on dialysis should not take Xyzal at all. For milder kidney impairment, the standard dose needs to be reduced, sometimes significantly. Someone with moderately reduced kidney function might only take it every other day, while someone with more severe impairment might only take it twice a week.
Children are held to an even stricter standard. Any child between 6 months and 11 years old with any degree of kidney impairment should not take Xyzal. Their smaller bodies and developing kidneys make dose adjustment unreliable, so the drug is simply off the table for that group.
Urinary Retention Risks
If you have an enlarged prostate, a spinal cord injury, or any other condition that already makes it harder to fully empty your bladder, Xyzal can make the problem worse. Like other antihistamines, it has mild effects on the muscles that control urination. For most people this is unnoticeable, but if you’re already prone to urinary retention, it can tip you over the edge into a painful inability to urinate. If that happens, you need to stop taking it.
Pregnancy and Breastfeeding
Xyzal does pass into breast milk. Among antihistamines, cetirizine (the closely related parent drug of levocetirizine) and loratadine are considered the preferred choices during breastfeeding because they’ve been studied more extensively. Loratadine, for example, transfers less than 1.1% of the mother’s dose into breast milk. Either way, infants should be monitored for unusual drowsiness or irritability. Antihistamines at normal doses are unlikely to reduce milk production once breastfeeding is well established, typically after the first six to eight weeks.
Stopping Xyzal After Long-Term Use
A safety update added to the Xyzal label in 2025 warns about a withdrawal effect that surprises many people. Some patients who took Xyzal for months or years developed intense, widespread itching within days of stopping, even if they never had itching before starting the medication. The itching can be severe enough to require restarting the drug or tapering off gradually rather than stopping abruptly. If you’ve been taking Xyzal daily for a long time, talk to your pharmacist about stepping down your dose rather than quitting cold turkey.
Other Antihistamines
You should avoid doubling up on antihistamines unless specifically directed to. Xyzal is the active half of cetirizine (Zyrtec), so taking both is essentially taking a double dose. Similarly, stacking Xyzal with other long-acting antihistamines like fexofenadine (Allegra) or loratadine (Claritin) increases the chance of side effects without providing much additional allergy relief. The same goes for nighttime cold medicines that already contain an antihistamine like diphenhydramine or doxylamine.