Can Levocetirizine (Xyzal) and Hydroxyzine be taken together?

From the Guidelines

Taking Xyzal (levocetirizine) and hydroxyzine together is not recommended due to the increased risk of sedation, performance impairment, and anticholinergic effects, as highlighted in the study by 1. When considering the use of these medications together, it's essential to weigh the potential benefits against the risks. Xyzal is a second-generation antihistamine that is generally preferred over first-generation antihistamines like hydroxyzine due to its lower likelihood of causing sedation, performance impairment, and anticholinergic effects 1. Some key points to consider when evaluating the use of Xyzal and hydroxyzine together include:

• The potential for increased sedation and drowsiness, as both medications have sedative properties, with hydroxyzine having stronger sedative effects 1
• The risk of performance impairment, which can exist without subjective awareness of drowsiness, and can be exacerbated by concomitant use of other CNS-active substances 1
• The potential for anticholinergic effects, including dryness of mouth and eyes, constipation, inhibition of micturition, and an increased risk for provocation of narrow angle glaucoma 1
• The increased sensitivity of older adults to the psychomotor impairment promoted by first-generation antihistamines, and their increased risk for complications such as fractures and subdural hematomas caused by falls 1 Given the potential risks and side effects associated with the combination of Xyzal and hydroxyzine, it is recommended to avoid using these medications together, and instead consider alternative treatment options that minimize the risk of sedation, performance impairment, and anticholinergic effects.

From the FDA Drug Label

THE POTENTIATING ACTION OF HYDROXYZINE MUST BE CONSIDERED WHEN THE DRUG IS USED IN CONJUNCTION WITH CENTRAL NERVOUS SYSTEM DEPRESSANTS Avoid cetirizine or levocetirizine in patients who have experienced AGEP or other hypersensitivity reactions with hydroxyzine, due to the risk of cross-sensitivity.

The use of Xyzal (levocetirizine) and hydroxyzine together is not recommended due to the risk of cross-sensitivity and potential for increased central nervous system depression.

• Key considerations:
  • Risk of cross-sensitivity between hydroxyzine and levocetirizine
  • Potential for increased central nervous system depression when used concomitantly 2
  • Contraindication of hydroxyzine in patients with known hypersensitivity to cetirizine or levocetirizine 2

From the Research

Combination of XYZAL (Levocetirizine) and Hydroxyzine

• The combination of levocetirizine and hydroxyzine has been studied in the context of treating chronic spontaneous urticaria (CSU) 3, 4.
• A study published in 2014 found that adding hydroxyzine to levocetirizine did not improve treatment efficacy, but increased daytime somnolence 3.
• Another study published in 2022 compared the effectiveness of bilastine, fexofenadine, and levocetirizine, and found that adding hydroxyzine to levocetirizine did not provide significant benefits in terms of urticaria symptoms or quality of life 4.

Pharmacological Properties

• Levocetirizine is a zwitterionic antihistamine with a slower dissociation rate from the H1 receptor compared to hydroxyzine, making it an insurmountable antagonist 5.
• The pharmacokinetics of levocetirizine differ from those of hydroxyzine, with lower CNS penetration and negligible interaction with liver enzymes 5.

Clinical Efficacy and Safety

• Studies have shown that levocetirizine is effective in treating CSU, with a marginal advantage in terms of antipruritic effect compared to cetirizine 6.
• The combination of levocetirizine and hydroxyzine may increase the risk of somnolence, but the overall safety profile of levocetirizine is generally favorable 3, 4.