Xyzal (levocetirizine dihydrochloride)
Company: UCB Inc.
Approval Status: Approved May 2007
Treatment for: seasonal and perennial allergic rhinitis and urticaria
Areas: Dermatology/Plastic Surgery; Immunology/Infectious Diseases; Otolaryngology; Pediatrics/Neonatology; Pulmonary/Respiratory Diseases
| General Information | Clinical Results | Side Effects | Mechanism of Action | Literature References | Additional Information |
General Information
The active component of Xyzal, Levocetirizine dihydrochloride, is an anti-histamine. It is an orally active and selective H1-receptor antagonist. Histamines act on H1 receptors, causing the symptoms commonly seen in allergic reactions. Xyzal inhibits these H1 receptors.
Xyzal is specifically indicated for the relief of symptoms associated with allergic rhinitis (seasonal and perennial) in adults and children 6 years of age and older. Xyzal is also indicated for the treatment of the uncomplicated skin manifestations of chronic idiopathic urticaria in adults and children 6 years of age and older.
Xyzal is supplied as a 5 mg tablet designed for oral administration. The recommended initial dose of Xyzal in adults and children aged 12 years and older is 5 mg once daily in the evening. Some patients may be adequately controlled by 2.5 mg once daily in the evening. The recommended initial dose of Xyzal in children 6 to 11 years old is 2.5 mg (1/2 tablet) once daily in the evening. The 2.5 mg dose should not be exceeded because the systemic exposure with 5 mg is approximately twice that of adults.
Clinical Results
FDA Approval
FDA approval of Xyzal was based on the results of several clinical
trials.
Seasonal and Perennial Allergic Rhinitis
Adults and Adolescents 12 Years of Age and Older
FDA approval was based on the results of six randomized,
placebo-controlled, double-blind clinical trials in adult and
adolescent patients 12 years and older with symptoms of seasonal
allergic rhinitis or perennial allergic rhinitis. Three of these
were dose-ranging trials of 2 to 4 weeks duration, one was a 2-week
efficacy trial in patients with seasonal allergic rhinitis and two
were efficacy trials (one 6-week and one 6- month) in patients with
perennial allergic rhinitis. The trials enrolled a total of 2,412
subjects. Efficacy was assessed using a total symptom score from
patient recording of 4 symptoms (sneezing, rhinorrhea, nasal
pruritus, and ocular pruritus) in five studies and 5 symptoms
(sneezing, rhinorrhea, nasal pruritus, ocular pruritus, and nasal
congestion) in one study. Symptoms were recorded using a 0 (absent)
to 3 (severe) categorical scale once daily in the evening,
reflective of the 24 hour treatment period. The primary endpoint
was the mean total symptom score averaged over the first week and
over 2 weeks for seasonal allergic rhinitis trials, and 4 weeks for
perennial allergic rhinitis trials.
The three dose ranging trials were conducted to evaluate the efficacy of Xyzal 2.5, 5, and 10 mg once daily in the evening. The seasonal allergic rhinitis trial was two weeks in duration and two trials were for perennial allergic rhinitis and were 4 weeks in duration. In these trials, each of the three doses of Xyzal demonstrated greater decrease in the reflective total symptom score than placebo and the difference was statistically significant for all three doses in two of the studies (p=<0.001).
The two week efficacy trial was designed to evaluate the efficacy of Xyzal 5 mg once daily in the evening compared with placebo in subjects with seasonal allergic rhinitis. Xyzal demonstrated a greater decrease from baseline in the reflective and instantaneous total symptom score than placebo, and the difference was statistically significant (p=0.011).
The 6-week trial was designed to compare the efficacy of Xyzal 5 mg once daily in the evening compared to placebo in patients with perennial allergic rhinitis. The 6-month trial was designed to compare efficacy over a six month treatment duration. Xyzal 5 mg demonstrated a greater decrease from baseline in the reflective total symptom score than placebo and the difference from placebo was statistically significant.
Pediatric Patients Aged 6 to 11 Years
No clinical trials were conducted with Xyzal 2.5 mg once daily in
pediatric subjects 6 to 11 years of age. Recommended dose was based
on cross-study comparison of the systemic exposure of Xyzal in
adults and pediatric subjects and on the safety profile of Xyzal in
both adult and pediatric subjects at doses equal to or higher than
the recommended dose for subjects 6 to 11 years. The safety of
Xyzal 5 mg once daily was evaluated in 243 pediatric subjects 6 to
12 years of age in two placebo controlled clinical trials lasting 4
and 6 weeks. The effectiveness of Xyzal 2.5 mg once daily for the
treatment of the symptoms of seasonal and perennial allergic
rhinitis and chronic idiopathic urticaria in pediatrics 6 to 11
years of age is supported by the extrapolation of demonstrated
efficacy of Xyzal 5 mg once daily in subjects 12 years of age and
older and by the pharmacokinetic comparison in adults and children.
Cross-study comparisons indicate that administration of a 5 mg dose
of Xyzal to 6 - 12 year old pediatric seasonal allergic rhinitis
subjects resulted in about 2-fold the systemic exposure (AUC)
observed when 5 mg of XYZAL was administered to healthy adult
subjects.
Chronic Idiopathic Urticaria
Adult Patients 18 Years of Age and Older
FDA approval for Xyzal in the treatment of urticaria was based on
the results of two multi-center, randomized, placebo-controlled,
double-blind clinical trials. The two trials enrolled a total of
423 subjects aged 18 to 85 years. The trials included one 4-week
dose ranging trial and one 4-week single-dose level trial. Of the
423 subjects, 146 received Xyzal 5 mg once daily in the evening.
Efficacy was based on the recording of pruritus severity on a
severity score of 0 (absent) to 3 (severe).The primary efficacy
endpoint was the mean reflective pruritus severity score over the
first week and over the entire treatment period. Additional
efficacy ebdpoints included instantaneous pruritus severity score,
the number and size of wheals, and duration of pruritus.
The dose-ranging trial was conducted to evaluate Xyzal 2.5, 5, and
10 mg once daily in the evening. In this trial, each of the three
doses of Xyzal demonstrated greater decrease in the reflective
pruritus severity score than placebo and the difference was
statistically significant for all three doses (p=<0.001).
The single dose trial evaluated the efficacy of Xyzal 5 mg once
daily in the evening compared to placebo in subjects with chronic
idiopathic urticaria over a 4-week treatment period. Xyzal 5 mg
demonstrated a greater decrease from baseline in the reflective
pruritus severity score than placebo and the difference from
placebo was statistically significant (p=<0.001). The secondary
endpoints also showed significant improvement over placebo.
Pediatric Patients
No clinical trials were conducted in pediatric subjects with
chronic idiopathic urticaria. However as stated above, safety and
efficacy data were extrapolated from cross-comparison studies.
Ongoing Study Commitments
- UCB has agreed to a deferred pediatric study under PREA for the
treatment of symptoms of perennial allergic rhinitis in pediatric
patients ages 0 to <6 years of age.
Final Report Submission: May 31, 2009 - UCB has agreed to a deferred pediatric study under PREA for the
treatment of symptoms of seasonal allergic rhinitis in pediatric
patients ages 2 to <6 years of age.
Final Report Submisison: May 31, 2009 - UCB has agreed to a deferred pediatric study under PREA for the
treatment of chronic idiopathic urticaria in pediatric patients
ages 0 to <6 years of age.
Final Report Submission: May 31, 2009
Side Effects
Adverse events associated with the use of Xyzal in adult and pediatric subjects aged 12 years and older may include, but are not limited to, the following:
- Somnolence
- Nasopharyngitis
- Fatigue
- Dry Mouth
- Pharyngitis
Adverse events associated with the use of Xyzal in pediatric subjects aged 6 to 12 years may include, but are not limited to, the following:
- Pyrexia
- Cough
- Somnolence
- Epistaxis
Mechanism of Action
The active component of Xyzal, Levocetirizine dihydrochloride, is the R enantiomer of cetirizine hydrochloride, a racemic compound with antihistaminic properties. It is an orally active and selective H1-receptor antagonist. Histamines act on H1 receptors, causing the symptoms commonly seen in allergic reactions. Xyzal inhibits these H1 receptors.
Literature References
Pasquali M, Baiardini I, Rogkakou A, Riccio AM, Gamalero C, Descalzi D, Folli C, Passalacqua G, Canonica GW Levocetirizine in persistent allergic rhinitis and asthma: effects on symptoms, quality of life and inflammatory parameters. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 2006 Sep;36(9):1161-7
Walter Canonica G, Bousquet J, Van Hammée G, Bachert C, Durham SR, Klimek L, Mullol J, Van Cauwenberge PB; XPERT Study Group Levocetirizine improves health-related quality of life and health status in persistent allergic rhinitis. Respiratory medicine 2006 Oct;100(10):1706-15.
Kapp A, Pichler WJ Levocetirizine is an effective treatment in patients suffering from chronic idiopathic urticaria: a randomized, double-blind, placebo-controlled, parallel, multicenter study. International journal of dermatology 2006 Apr;45(4):469-74
Potter PC; Paediatric Levocetirizine Study Group Efficacy and safety of levocetirizine on symptoms and health-related quality of life of children with perennial allergic rhinitis: a double-blind, placebo-controlled randomized clinical trial. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology 2005 Aug;95(2):175-80
Simons FE, Simons KJ Levocetirizine: pharmacokinetics and pharmacodynamics in children age 6 to 11 years. The Journal of allergy and clinical immunology 2005 Aug;116(2):355-61
de Blic J, Wahn U, Billard E, Alt R, Pujazon MC Levocetirizine in children: evidenced efficacy and safety in a 6-week randomized seasonal allergic rhinitis trial. Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology 2005 May;16(3):267-75
Benedetti MS, Plisnier M, Kaise J, Maier L, Baltes E, Arendt C, McCracken N Absorption, distribution, metabolism and excretion of [14C]levocetirizine, the R enantiomer of cetirizine, in healthy volunteers. European journal of clinical pharmacology 2001 Oct;57(8):571-82
Additional Information
For additional information regarding Xyzal or seasonal and perennial allergic rhinitis and urticaria, please visit the Xyzal web page.
The FDA drug information shown here is licensed from Thomson CenterWatch. The information provided here is for general educational purposes only and does not constitute medical or pharmaceutical advice which should be sought from qualified medical and pharmaceutical advisers.
