Xyzal Information
Xyzal (Levocetirizine) Dosage And Administration
Xyzal (Levocetirizine) is available as 2.5 mg/5 mL (0.5 mg/mL) oral solution and as 5 mg breakable (scored) tablets, allowing for the administration of 2.5 mg, if needed. Xyzal (Levocetirizine) can be taken without regard to food consumption.
In adults and children 12 years of age and older with:
No dose adjustment is needed in patients with solely hepatic impairment. In patients with both hepatic impairment and renal impairment, adjustment of the dose is recommended.
Xyzal (Levocetirizine) Dosage Forms And Strengths
Xyzal (Levocetirizine) oral solution is a clear, colorless liquid containing 0.5 mg of levocetirizine dihydrochloride per mL.
Xyzal (Levocetirizine) tablets are white, film-coated, oval-shaped, scored, imprinted (with the letter Y in red color on both halves of the scored tablet) and contain 5 mg levocetirizine dihydrochloride.
Xyzal (Levocetirizine) Contraindications
The use of Xyzal (Levocetirizine) is contraindicated in:
Xyzal (Levocetirizine) Adverse Reactions
Use of Xyzal (Levocetirizine) has been associated with somnolence, fatigue, and asthenia [see ].
The safety data described below reflect exposure to Xyzal (Levocetirizine) in 2708 patients with seasonal or perennial allergic rhinitis or chronic idiopathic urticaria in 14 controlled clinical trials of 1 week to 6 months duration.
The short-term (exposure up to 6 weeks) safety data for adults and adolescents are based upon eight clinical trials in which 1896 patients (825 males and 1071 females aged 12 years and older) were treated with Xyzal (Levocetirizine) 2.5, 5, or 10 mg once daily in the evening.
The short-term safety data from pediatric patients are based upon two clinical trials in which 243 children with seasonal or perennial allergic rhinitis (162 males and 81 females 6 to 12 years of age) were treated with Xyzal (Levocetirizine) 5 mg once daily for 4 to 6 weeks, one clinical trial in which 114 children (65 males and 49 females 1 to 5 years of age) with allergic rhinitis or chronic idiopathic urticaria were treated with Xyzal (Levocetirizine) 1.25 mg twice daily for 2 weeks, and one clinical trial in which 45 children (28 males and 17 females 6 to 11 months of age) with symptoms of allergic rhinitis or chronic urticaria were treated with Xyzal (Levocetirizine) 1.25 mg once daily for 2 weeks.
The long-term (exposure of 4 or 6 months) safety data in adults and adolescents are based upon two clinical trials in which 428 patients (190 males and 238 females) with allergic rhinitis were exposed to treatment with Xyzal (Levocetirizine) 5 mg once daily. Long term safety data are also available from an 18-month trial in 255 Xyzal (Levocetirizine) -treated subjects 12-24 months of age.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trial of another drug and may not reflect the rates observed in practice.
In addition to the adverse reactions reported during clinical trials and listed above, adverse events have also been identified during post-approval use of Xyzal (Levocetirizine) in other countries. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Adverse events of hypersensitivity and anaphylaxis, angioedema, fixed drug eruption, pruritus, rash, and urticaria, convulsion, paraesthesia, dizziness, aggression and agitation, hallucinations, depression, visual disturbances, blurred vision, palpitations, tachycardia, dyspnea, nausea, vomiting, hepatitis, dysuria, and myalgia have been reported.
Besides these events reported under treatment with Xyzal (Levocetirizine) , other potentially severe adverse events have been reported from the post-marketing experience with cetirizine. Since levocetirizine is the principal pharmacologically active component of cetirizine, one should take into account the fact that the following adverse events could also potentially occur under treatment with Xyzal (Levocetirizine) : suicidal ideation, orofacial dyskinesia, severe hypotension, cholestasis, glomerulonephritis, and still birth.
Xyzal (Levocetirizine) Drug Interactions
Xyzal (Levocetirizine) Use In Specific Populations
The recommended dose of Xyzal (Levocetirizine) for the treatment of the uncomplicated skin manifestations of chronic idiopathic urticaria in patients 6 months to 17 years of age is based on extrapolation of efficacy from adults 18 years of age and older [see ].
The recommended dose of Xyzal (Levocetirizine) in patients 6 months to 11 years of age for the treatment of the symptoms of perennial allergic rhinitis and chronic idiopathic urticaria and in patients 2 to 11 years of age for the treatment of symptoms of seasonal allergic rhinitis is based on cross-study comparisons of the systemic exposure of Xyzal (Levocetirizine) in adults and pediatric patients and on the safety profile of Xyzal (Levocetirizine) in both adult and pediatric patients at doses equal to or higher than the recommended dose for patients 6 months to 11 years of age.
The safety of Xyzal (Levocetirizine) 5 mg once daily was evaluated in 243 pediatric patients 6 to 12 years of age in two placebo-controlled clinical trials lasting 4 and 6 weeks. The safety of Xyzal (Levocetirizine) 1.25 mg twice daily was evaluated in one 2-week clinical trial in 114 pediatric patients 1 to 5 years of age and the safety of Xyzal (Levocetirizine) 1.25 mg once daily was evaluated in one 2-week clinical trial in 45 pediatric patients 6 to 11 months of age [see ].
The effectiveness of Xyzal (Levocetirizine) 1.25 mg once daily (6 months to 5 years of age) and 2.5 mg once daily (6 to 11 years of age) for the treatment of the symptoms of seasonal and perennial allergic rhinitis and chronic idiopathic urticaria is supported by the extrapolation of demonstrated efficacy of Xyzal (Levocetirizine) 5 mg once daily in patients 12 years of age and older based on the pharmacokinetic comparison between adults and children.
Cross-study comparisons indicate that administration of a 5 mg dose of Xyzal (Levocetirizine) to 6 to 12 year old pediatric seasonal allergic rhinitis patients resulted in about 2-fold the systemic exposure (AUC) observed when 5 mg of Xyzal (Levocetirizine) was administered to healthy adults. Therefore, in children 6 to 11 years of age the recommended dose of 2.5 mg once daily should not be exceeded. In a population pharmacokinetics study the administration of 1.25 mg once daily in children 6 months to 5 years of age resulted in systemic exposure comparable to 5 mg once daily in adults. [see and].
Xyzal (Levocetirizine) Overdosage
Overdosage has been reported with Xyzal (Levocetirizine) .
Symptoms of overdose may include drowsiness in adults and initially agitation and restlessness, followed by drowsiness in children. There is no known specific antidote to Xyzal (Levocetirizine) . Should overdose occur, symptomatic or supportive treatment is recommended. Xyzal (Levocetirizine) is not effectively removed by dialysis, and dialysis will be ineffective unless a dialyzable agent has been concomitantly ingested.
The acute maximal non-lethal oral dose of levocetirizine was 240 mg/kg in mice (approximately 190 times the maximum recommended daily oral dose in adults, approximately 230 times the maximum recommended daily oral dose in children 6 to 11 years of age, and approximately 180 times the maximum recommended daily oral dose in children 6 months to 5 years of age on a mg/m basis). In rats the maximal non-lethal oral dose was 240 mg/kg (approximately 390 times the maximum recommended daily oral dose in adults, approximately 460 times the maximum recommended daily oral dose in children 6 to 11 years of age, and approximately 370 times the maximum recommended daily oral dose in children 6 months to 5 years of age on a mg/m basis).
Xyzal (Levocetirizine) Description
Levocetirizine dihydrochloride, the active component of Xyzal (Levocetirizine) tablets and oral solution, is an orally active H-receptor antagonist. The chemical name is (R)-[2-[4-[(4-chlorophenyl) phenylmethyl]-1-piperazinyl] ethoxy] acetic acid dihydrochloride. Levocetirizine dihydrochloride is the R enantiomer of cetirizine hydrochloride, a racemic compound with antihistaminic properties. The empirical formula of levocetirizine dihydrochloride is CHClNO•2HCl. The molecular weight is 461.82 and the chemical structure is shown below:
Levocetirizine dihydrochloride is a white, crystalline powder and is water soluble.
Xyzal (Levocetirizine) 5 mg tablets are formulated as immediate release, white, film-coated, oval-shaped scored tablets for oral administration. The tablets are imprinted on both halves of the scored line with the letter Y in red (Opacode Red). Inactive ingredients are: microcrystalline cellulose, lactose monohydrate, colloidal anhydrous silica, and magnesium stearate. The film coating contains hypromellose, titanium dioxide, and macrogol 400.
Xyzal (Levocetirizine) 0.5 mg/mL oral solution is formulated as an immediate release, clear, colorless liquid. Inactive ingredients are: sodium acetate trihydrate, glacial acetic acid, maltitol solution, glycerin, methylparaben, propylparaben, saccharin, flavoring (consisting of triacetin, natural & artificial flavors, dl-alpha-tocopherol), purified water.
Xyzal (Levocetirizine) Clinical Pharmacology
Studies in adult healthy subjects showed that levocetirizine at doses of 2.5 mg and 5 mg inhibited the skin wheal and flare caused by the intradermal injection of histamine. In contrast, dextrocetirizine exhibited no clear change in the inhibition of the wheal and flare reaction. Levocetirizine at a dose of 5 mg inhibited the wheal and flare caused by intradermal injection of histamine in 14 pediatric subjects (aged 6 to 11 years) and the activity persisted for at least 24 hours. The clinical relevance of histamine wheal skin testing is unknown.
A QT/QTc study using a single dose of 30 mg of levocetirizine did not demonstrate an effect on the QTc interval. While a single dose of levocetirizine had no effect, the effects of levocetirizine may not be at steady state following single dose. The effect of levocetirizine on the QTc interval following multiple dose administration is unknown. Levocetirizine is not expected to have QT/QTc effects because of the results of QTc studies with cetirizine and the long post-marketing history of cetirizine without reports of QT prolongation.
Xyzal (Levocetirizine) Nonclinical Toxicology
No carcinogenicity studies have been performed with levocetirizine. However, evaluation of cetirizine carcinogenicity studies are relevant for determination of the carcinogenic potential of levocetirizine. In a 2-year carcinogenicity study, in rats, cetirizine was not carcinogenic at dietary doses up to 20 mg/kg (approximately 15 times the maximum recommended daily oral dose in adults, approximately 10 times the maximum recommended daily oral dose in children 6 to 11 years of age and approximately 15 times the maximum recommended daily oral dose in children 6 months to 5 years of age on a mg/m basis). In a 2-year carcinogenicity study in mice, cetirizine caused an increased incidence of benign hepatic tumors in males at a dietary dose of 16 mg/kg (approximately 6 times the maximum recommended daily oral dose in adults, approximately 4 times the maximum recommended daily oral dose in children 6 to 11 years of age, and approximately 6 times the maximum recommended daily oral dose in children 6 months to 5 years of age on a mg/m basis). No increased incidence of benign tumors was observed at a dietary dose of 4 mg/kg (approximately 2 times the maximum recommended daily oral dose in adults, equivalent to the maximum recommended daily oral dose in children 6 to 11 years of age and approximately 2 times the maximum recommended daily oral dose in children 6 months to 5 years of age on a mg/m basis). The clinical significance of these findings during long-term use of Xyzal (Levocetirizine) is not known.
Levocetirizine was not mutagenic in the Ames test, and not clastogenic in the human lymphocyte assay, the mouse lymphoma assay, and micronucleus test in mice.
In a fertility and general reproductive performance study in mice, cetirizine did not impair fertility at an oral dose of 64 mg/kg (approximately 25 times the recommended daily oral dose in adults on a mg/m basis).
Xyzal (Levocetirizine) How Supplied/storage And Handling
Xyzal (Levocetirizine) tablets are white, film-coated, oval-shaped, scored, imprinted (with the letter Y in red color on both halves of the scored tablet) and contain 5 mg levocetirizine dihydrochloride. They are supplied in unit of use HDPE bottles.
90 Tablets (NDC 0024-5800-90)
Xyzal (Levocetirizine) oral solution is a clear, colorless liquid containing 0.5 mg of levocetirizine dihydrochloride per mL.
Oral solution in 5 oz glass bottles (NDC 0024-5801-20)
Oral Solution in 5 oz polypropylene bottles (NDC 0024-5801-21)
Xyzal (Levocetirizine)
Xyzal (Levocetirizine)
Xyzal (Levocetirizine)
