Cetirizine vs levocetirizine: two widely used antihistamines, but subtle differences in sedation and potency. AI image
Pharmacy

Cetirizine vs Levocetirizine: Which Antihistamine Is Better?

A Comparison Guide to First-Generation Antihistamines

Author : Vanshika Kalra

Cetirizine and levocetirizine both belong to the class of medicines known as antihistamines. According to the NHS, antihistamines are commonly used to relieve symptoms of allergies such as hay fever, hives, conjunctivitis, and reactions to insect bites or stings.

Types of Antihistamine

Before understanding cetirizine and levocetirizine, it is important to understand about the types of antihistamines in general. Antihistamines are mainly divided into two subtypes: H1 and H2 antihistamines.

H1 Antihistamines (H1 receptor antagonists) 

These are indicated for allergic rhinitis, conjunctivitis, dermatologic reactions, sinusitis, acute and chronic urticaria, angioedema, atopic dermatitis, adjunct therapy, bronchitis (symptomatic), and motion sickness.

H2 Antihistamines (H2 receptor antagonists)

These are indicated for peptic ulcer disease, gastroesophageal reflux disease, gastritis, and Zollinger-Ellison syndrome.

H1 antihistamines include first and second generation, also termed as sedating and non-sedating antihistamines respectively.1

Cetirizine and levocetirizine both belong to second generation antihistamines.

Understanding Cetirizine and Levocetirizine

Cetirizine is a racemic mixture of enantiomers.

Cetirizine is considered one of the most potent second-generation antihistamines, based on surrogate markers of effectiveness such as suppression of skin reactivity to histamine.

Levocetirizine, a newer antihistamine, is the R-enantiomer of cetirizine. Cetirizine is a racemic mixture, meaning it contains two mirror-image forms, whereas levocetirizine represents the pharmacologically active form. Studies evaluating histamine suppression have shown that 2.5 mg of levocetirizine is comparable to 5 mg of cetirizine, suggesting that most of cetirizine’s antihistaminic activity is attributable to its levocetirizine enantiomer. 2

Mechanism of Action of Cetirizine and Levocetirizine

H1 receptors play a role in mediating allergic reactions, including vasodilation, bronchoconstriction, pruritus, and central nervous system (CNS) wakefulness. H1 antihistamines act by blocking these receptors, thereby reducing allergic symptoms.

Second-generation antihistamines such as cetirizine and levocetirizine primarily act on peripheral H1 receptors. They have longer half-lives, improved tolerability, and cause less sedation compared to first-generation antihistamines. 1

Cetirizine vs Levocetirizine: Clinical Indications

Cetirizine (Zyrtec)

  • Relief of seasonal and perennial allergic rhinitis

  • Chronic idiopathic urticaria

  • Intravenous formulation for acute urticaria 1

Levocetirizine (Xyzal)

  • Relief of seasonal and perennial allergic rhinitis

  • Uncomplicated skin manifestations of chronic idiopathic urticaria1

When to Choose Cetirizine vs Levocetirizine

In a discussion on MedBound Hub, Dr. Nischal Agrawal, Pharm D, Krupanidhi College of Pharmacy, Bengaluru, shared insights on the clinical preference for both drugs.

Cetirizine Is Preferred When:

  • A cost-effective treatment is required

  • Mild to moderate allergy symptoms are present

  • Night-time dosing is acceptable

Levocetirizine Should Be Used When:

  • Daytime alertness is important (e.g., students, drivers)

  • Stronger symptom control is needed

  • A lower dose with improved efficacy is preferred

Expert Clinical Opinions on Cetirizine and Levocetirizine

Dr. Nischal Agrawal suggested:

"Both levocetirizine and cetirizine are effective in treating allergic conditions. Levocetirizine offers improved potency and reduced sedation, making it clinically useful for patients who require better symptom control with fewer side effects, whereas cetirizine remains a reliable and economical option."

Sanghavi N. Deshpande, Pharm D graduate, added:

"Levocetirizine would definitely be my drug of choice because it provides the required effect with less sedation and does not interfere with day-to-day activities, making it very helpful for working professionals and college-going individuals."

Clinical Study Findings on Cetirizine and Levocetirizine

A 2009 study3 comparing the efficacy of cetirizine and levocetirizine in chronic idiopathic urticaria concluded that:

  • The overall clinical efficacy of both drugs was comparable

  • Levocetirizine showed a marginal advantage in antipruritic effect, possibly at the cost of increased sedation

Key Takeaways on Cetirizine and Levocetirizine

Both cetirizine and levocetirizine are second-generation H1 antihistamines
Levocetirizine is the active R-enantiomer of cetirizine
Cetirizine is a more cost-effective option as compared to Levocetirizine
The choice of medication depends on symptom severity, patient lifestyle, and budget

References:

1. Farzam K, Sabir S, O'Rourke MC. Antihistamines. [Updated 2025 Dec 13]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK538188/

2. Tzanetos, Douglas B., John M. Fahrenholz, Theresa Scott, and Kristina Buchholz. 2011. “Comparison of the Sedating Effects of Levocetirizine and Cetirizine: A Randomized, Double-Blind, Placebo-Controlled Trial.” Annals of Allergy, Asthma & Immunology 107 (6): 517–522. https://doi.org/10.1016/j.anai.2011.08.012.

3. Garg, G., & Thami, G. P. (2007). Comparative efficacy of cetirizine and levocetirizine in chronic idiopathic urticaria. Journal of Dermatological Treatment, 18(1), 23–24. https://doi.org/10.1080/09546630601028745

Disclaimer: This article is for informational purposes only and should not replace professional medical advice. Always consult a healthcare provider before starting or changing any medication.

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