What is the difference between cetirizine (Zyrtec) and levocetirizine (Xyzal)?

Difference Between Cetirizine and Levocetirizine

Levocetirizine is the active R-enantiomer of cetirizine, meaning cetirizine contains both the active levocetirizine and the inactive dextrocetirizine in equal amounts, while levocetirizine contains only the pharmacologically active component at half the dose. 1, 2

Chemical and Pharmacological Differences

Structural relationship:

• Cetirizine is a racemic mixture containing 50% levocetirizine (R-enantiomer) and 50% dextrocetirizine (S-enantiomer) 1, 2
• Levocetirizine is the purified active enantiomer that provides essentially all the antihistaminic activity 1
• The inactive S-enantiomer (dextrocetirizine/ucb 28557) demonstrates no pharmacodynamic effect on histamine-induced responses 1

Receptor binding characteristics:

• Levocetirizine has a slower dissociation rate from the H1 receptor compared to cetirizine, making it an insurmountable antagonist with potentially longer duration of action 2
• Both compounds have high affinity for the H1 receptor, but levocetirizine's superior receptor occupancy may translate to enhanced clinical benefit 2, 3

Clinical Efficacy Comparisons

Dosing equivalence:

• Levocetirizine 2.5 mg demonstrates comparable antihistaminic activity to cetirizine 5 mg in histamine-induced wheal and flare suppression 1
• The standard dose of levocetirizine is 5 mg once daily, while cetirizine is typically dosed at 10 mg daily 4, 1

Duration of action:

• Levocetirizine showed mean wheal inhibition lasting 28.4 hours versus 24.4 hours for cetirizine 1
• Levocetirizine demonstrated superior area under the curve for antihistaminic effect compared to cetirizine, though maximum inhibition was equivalent 1

Contradictory evidence on comparative effectiveness:

• One pediatric study found cetirizine more efficacious than levocetirizine for perennial allergic rhinitis at weeks 8 and 12, with better improvement in nasal peak expiratory flow rate 5
• However, a chronic urticaria study found comparable clinical efficacy between the two agents, with levocetirizine showing marginally better antipruritic effect but increased sedation 6
• The weight of evidence from pharmacokinetic studies suggests levocetirizine should theoretically be superior due to elimination of the inactive enantiomer 1, 2

Pharmacokinetic Properties

Absorption and distribution:

• Both agents exhibit high intestinal absorption (>70% oral bioavailability) and high plasma protein binding (88-96%) 2
• Levocetirizine has a half-life of approximately 7 hours in humans 2
• Both compounds have minimal hepatic metabolism and are excreted predominantly unchanged in urine 1, 2

CNS penetration:

• Both agents have low CNS penetration due to their zwitterionic structure and P-glycoprotein activity, distinguishing them from first-generation antihistamines 2

Side Effect Profile

Sedation potential:

• Cetirizine 10 mg may cause mild drowsiness in 13.7% of patients versus 6.3% with placebo 7
• Levocetirizine showed marginally increased sedation compared to cetirizine in one comparative study 6
• Both agents are significantly less sedating than first-generation antihistamines 7, 2

Special Population Considerations

Renal impairment:

• Both cetirizine and levocetirizine doses should be halved in moderate renal impairment 7
• Both should be avoided in severe renal impairment (creatinine clearance <10 mL/min) 7
• Contraindicated if patient has kidney disease 4

Pregnancy:

• Both cetirizine and levocetirizine are FDA Pregnancy Category B drugs 7
• Ideally avoid all antihistamines in pregnancy, especially first trimester 7

Anti-inflammatory Properties

Additional therapeutic effects:

• Levocetirizine demonstrates documented anti-inflammatory effects at clinically relevant concentrations beyond simple H1 receptor blockade 3
• These anti-inflammatory properties may enhance therapeutic benefit for long-term allergic disease management 3

Common Pitfalls

• Do not assume levocetirizine is always superior clinically despite theoretical pharmacological advantages—individual patient response varies and some studies show cetirizine performing equally or better 5, 6
• Avoid using standard cetirizine doses in renal impairment without dose adjustment, as both agents require halving the dose 7
• Do not overlook that levocetirizine may cause more sedation in some patients despite being the "purified" enantiomer 6