Xyzal (levocetirizine)

Conclusion

Xyzal is a new antihistamine whose active ingredient – levocetirizine – is the active enantiomer of the already known antihistamine cetirizine (Zyrtec). Xyzal has not been shown to have any advantage over Zyrtec - not with respect to clinical efficacy, adverse drug reactions or cost. The only factor that may have an impact on physician or patient choice is that Zyrtec is an over-the-counter product, while Xyzal is prescription-only.

Background

Xyzal is a new antihistamine marketed in Denmark since 4 February 2001. Its active ingredient, levocetirizine, is the R-enantiomer of cetirizine, and is thus as such not a new compound, but part of an already known preparation. Cetirizine consists of equal parts R- and S-enantiomer, but several studies have shown that the pharmacological effect – a selective inhibitory effect on the peripheral H1 receptors – is induced by the R-enantiomer alone. Studies with healthy volunteers have shown that levocetirizine does not differ significantly from cetirizine pharmacokinetically. With both products, there is a rapid and almost complete uptake of the drug; it is metabolised to a very limited extent and has a high renal clearance. It has been shown that no chiral inversion occurs, i.e. the R-enantiomer is not converted into an S-enantiomer after ingestion.

Xyzal tablets contain 5 mg levocetirizine, which corresponds to the content of active R-enantiomer in one 10 mg cetirizine tablet.

Efficacy

The clinical efficacy of 5 mg levocetirizine has been compared with that of 10 mg cetirizine in a single clinical study in which the products were given to patients with seasonal allergic rhinitis. The results showed that there was no difference between the two therapies. The clinical efficacy of levocetirizine has also been demonstrated in two dose-response studies which also included placebo groups.

Adverse drug reactions

Adverse reactions are the same as for cetirizine. At a dose of 5 mg, the incidence of slightly sedating adverse drug reactions (somnolence, fatigue and asthenia) was higher in patients receiving levocetirizine than in those receiving placebo (10.2% versus 4.4%). No risk of cardiac arrhythmia or change in QT interval after administration of cetirizine has been demonstrated, and a review of ECGs from a total of 44 healthy volunteers who had received levocetirizine found no prolongation of their average QT intervals.

Drug interactions

Like cetirizine, levocetirizine is to a high degree excreted unchanged: less than 14% of a given dose is converted into metabolites. There are several different metabolic pathways, including through the CYP1A2, 2C9, 2C19, 2D6, 2E1 and 3A4t pathways in the liver. A total of 13 different metabolites have been observed. In vitro studies have shown that levocetirizine does not affect the CYP isoenzymes of the liver, and the risk of interactions in connection with metabolism is considered to be very low.

There is a risk of interaction if the drug is used concurrently with alcohol or other CNS depressants.

Cost

Xyzal costs roughly the same as Zyrtec and is in the same price range as the other non-sedating antihistamines. Below is a table comparing the price of levocetirizine with that of some of the other non-sedating antihistamines that the Institute has previously recommended as first-line drugs. Prices are as at 4 February 2002.

Product	Strength and pack size	Prescription and reimbursement status	Cost per tablet (DKK)
Levocetirizine
Xyzal tablets	5 mg, 10 tablets 5 mg, 30 tablets	Prescription; general reimbursement	5.98 4.56
Cetirizine
Zyrtec tablets	10 mg, 7 tablets 10 mg, 30 tablets 10 mg, 90 tablets	OTC; reimbursement for pensioners and patients with a chronic disease	6.34 4.07 3.22
Alnok tablets	10 mg, 10 tablets 10 mg. 30 tablets 10 mg, 90 tablets		5.65 4.10 3.06
Loratadine
Clarityn tablets	10 mg, 10 tablets 10 mg, 30 tablets (Orifarm) 10 mg, 100 tablets (Orifarm)	OTC; reimbursement for pensioners and patients with a chronic disease	5.35 3.15 2.51
Versal tablets	10 mg, 10 tablets 10 mg, 30 tablets		5.35 4.40
Geklimon	10 mg, 10 tablets 10 mg, 30 tablets 10 mg, 100 tablets		5.52 3.58 3.01
Desloratadine
Aerius	5 mg, 10 tablets 5 mg, 30 tablets 5 mg, 100 tablets	Prescription; general reimbursement	6.33 5.03 4.09
Fexofenadine
Telfast	120 mg, 10 tablets 120 mg, 30 tablets 120 mg, 100 tablets 180 mg, 10 tablets 180 mg, 30 tablets 180 mg, 100 tablets	Prescription; general reimbursement	5.91 4.72 4.07 7.53 6.07 5.42

Additional information is available from the summary of product characteristics published by the Danish Medicines Agency (Danish only).