Won't hurt you:But not FDA recommended. Rizal is indicated for the relief of symptoms associated with perennial allergic rhinitis in children 6 months to 2 years of age.
Rizal is indicated for the treatment of the uncomplicated skin manifestations of chronic idiopathic urticaria in adults and children 6 months of age and older. The recommended initial dose of Rizal is 1.25 mg (1/2 teaspoon oral solution) (2.5 mL) once daily in the evening.
The recommended dose of Rizal is 5 mg (1 tablet or 2 teaspoons oral solution) once daily in the evening. Some patients may be adequately controlled by 2.5 mg (1/2 tablet or 1 teaspoon oral solution) once daily in the evening.
The recommended dose of Rizal is 2.5 mg (1/2 tablet or 1 teaspoon oral solution) once daily in the evening. The recommended initial dose of Rizal is 1.25 mg (1/2 teaspoon oral solution) (2.5 mL) once daily in the evening.
Mild renal impairment (creatinine clearance = 50–80 mL/min): a dose of 2.5 mg once daily is recommended; Moderate renal impairment (CL CR = 30–50 mL/min): a dose of 2.5 mg once every other day is recommended; Severe renal impairment (CL CR = 10–30 mL/min): a dose of 2.5 mg twice weekly (administered once every 3–4 days) is recommended; End-stage renal disease patients (CL CR <10 mL/min) and patients undergoing hemodialysis should not receive Rizal. Rizal oral solution is a clear, colorless liquid containing 0.5 mg of levocetirizine hydrochloride per mL.
In clinical trials the occurrence of somnolence, fatigue, and Athenian has been reported in some patients under therapy with Rizal. The safety data described below reflect exposure to Rizal in 2708 patients with 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 Rizal 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 allergic rhinitis (162 males and 81 females 6 to 12 years of age) were treated with Rizal 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 Rizal 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 Rizal 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 Rizal 5 mg once daily. Long term safety data are also available from an 18-month trial in 255 Rizal -treated subjects 12–24 months of age.
In placebo-controlled trials of 1–6 weeks in duration, the most common adverse reactions were somnolence, nasopharyngitis, fatigue, dry mouth, and pharyngitis, and most were mild to moderate in intensity. Table 1 lists adverse reactions that were reported in greater than or equal to 2% of subjects aged 12 years and older exposed to Rizal 2.5 mg or 5 mg in eight placebo-controlled clinical trials and that were more common with Rizal than placebo.
Additional adverse reactions of medical significance observed at a higher incidence than in placebo in adults and adolescents aged 12 years and older exposed to Rizal are syncope (0.2%) and weight increased (0.5%). A total of 243 pediatric patients 6 to 12 years of age received Rizal 5 mg once daily in two short-term placeboes controlled double-blind trials.
Table 2: Adverse Reactions Reported in 2% of Subjects Aged 6–12 Years Exposed to Rizal 5 mg Once Daily in Placebo-Controlled Clinical Trials 4 and 6 Weeks in DurationAdverse Reactions Rizal 5 mg (n = 243)Placebo (n = 240)Pyrexia10 (4%)5 (2%)Cough8 (3%)2 (<1%)Somnolence7 (3%)1 (<1%)Epistaxis6 (2%)1 (<1%) A total of 114 pediatric patients 1 to 5 years of age received Rizal 1.25 mg twice daily in a two week placebo-controlled double-blind safety trial.
Table 3: Adverse Reactions Reported in 2% of Subjects Aged 1–5 Years Exposed to Rizal 1.25 mg Twice Daily in a 2-Week Placebo-Controlled Clinical TrialAdverse Reactions Rizal 1.25 mg Twice Daily (n = 114)Placebo (n = 59)Pyrexia5 (4%)1 (2%)Diarrhea4 (4%)2 (3%)Vomiting4 (4%)2 (3%)Otis Media3 (3%)0 (0%) A total of 45 pediatric patients 6 to 11 months of age received Rizal 1.25 mg once daily in a two week placebo-controlled double-blind safety trial.
In two controlled clinical trials, 428 patients (190 males and 238 females) aged 12 years and older were treated with Rizal 5 mg once daily for 4 or 6 months. Ten (2.3%) patients treated with Rizal discontinued because of somnolence, fatigue or Athenian compared to 2 (<1%) in the placebo group.
There are no long term clinical trials in children below 12 years of age with allergic rhinitis or chronic idiopathic urticaria. Elevations of blood bilirubin and transaminase were reported in <1% of patients in the clinical trials.
Because these reactions 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. Since levocetirizine is the principal pharmacologically active component of satirizing, one should take into account the fact that the following adverse events could also potentially occur under treatment with Rizal.
In Vito data indicate that levocetirizine is unlikely to produce pharmacokinetic interactions through inhibition or induction of liver drug-metabolizing enzymes. There was a small decrease (~16%) in the clearance of satirizing caused by a 400 mg dose of theophylline.
Available data from published literature and postmarketing experience with levocetirizine use in pregnant women are insufficient to identify any drug-associated risks of miscarriage, birth defects, or adverse maternal or fetal outcomes. In animal reproduction studies, there was no evidence of fetal harm with administration of levocetirizine by the oral route to pregnant rats and rabbits, during the period of orangeness, at doses up to 390 times and 470 times, respectively, the maximum recommended human dose (MHD) in adults.
In rats treated during late gestation and the lactation period, satirizing had no effects on pup development at oral doses up to approximately 60 times the MHD in adults. In mice treated during late gestation and the lactation period, satirizing administered by the oral route to the dams had no effects on pup development at a dose that was approximately 25 times the MHD in adults; however, lower pup weight gain during lactation was observed at a dose that was 95 times the MHD in adults .
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
In mice and beagle dogs, studies indicated that satirizing was excreted in milk . No adverse developmental effects on pups were seen when satirizing was administered orally to dams during lactation at a dose that was approximately 25 times the MHD in adults .
Studies in beagle dogs indicated that approximately 3% of the dose of satirizing was excreted in milk. The recommended dose of Rizal 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 .
The recommended dose of Rizal in patients 6 months to 2 years of age for the treatment of the symptoms of perennial allergic rhinitis and 6 months to 11 years of age with chronic idiopathic urticaria is based on cross-study comparisons of the systemic exposure of Rizal in adults and pediatric patients and on the safety profile of Rizal 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 Rizal 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 Rizal 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 Rizal 1.25 mg once daily was evaluated in one 2-week clinical trial in 45 pediatric patients 6 to 11 months of age . The effectiveness of Rizal 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 perennial allergic rhinitis and chronic idiopathic urticaria is supported by the extrapolation of demonstrated efficacy of Rizal 5 mg once daily in patients 12 years of age and older based on the pharmacokinetic comparison between adults and children.
Therefore, in children 6 to 11 years of age the recommended dose of 2.5 mg once daily should not be exceeded. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.
In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. Rizal is known to be substantially excreted by the kidneys and the risk of adverse reactions to this drug may be greater in patients with impaired renal function.
Levocetirizine hydrochloride is the R enantiomer of satirizing hydrochloride, a race mic compound with antihistamines properties. Inactive ingredients are: microcrystalline cellulose, lactose monohydrate, colloidal anhydrous silica, and magnesium stearate.
Rizal 0.5 mg/mL oral solution is formulated as an immediate release, clear, colorless liquid. Inactive ingredients are: sodium acetate rehydrate, glacial acetic acid, mannitol solution, glycerin, methylparaben, propylparaben, saccharin, flavoring (consisting of Princeton, natural & artificial flavors, dl-alpha-tocopherol), purified water.
Levocetirizine, the active enantiomer of satirizing, is an antihistamine; its principal effects are mediated via selective inhibition of H receptors. In Vito binding studies revealed that levocetirizine has an affinity for the human H1-receptor 2-fold higher than that of satirizing (I = 3 MOL/L vs. 6 MOL/L, respectively).
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.
A QT/Etc study using a single dose of 30 mg of levocetirizine did not demonstrate an effect on the Etc interval. Levocetirizine exhibited linear pharmacokinetics over the therapeutic dose range in adult healthy subjects.
In adults, peak plasma concentrations are achieved 0.9 hour after administration of the oral tablet. The accumulation ratio following daily oral administration is 1.12 with steady state achieved after 2 days.
Peak concentrations are typically 270 NG/mL and 308 NG/mL following a single and a repeated 5 mg once daily dose, respectively. Dealkylation pathways are primarily mediated by CYP3A4 while aromatic oxidation involves multiple and/or unidentified CYP isoforms.
Data from a pediatric pharmacokinetic study with oral administration of a single dose of 5 mg levocetirizine in 14 children age 6 to 11 years with body weight ranging between 20 and 40 kg show that Max and AUC values are about 2-fold greater than that reported in healthy adult subjects in a cross-study comparison. The mean Max was 450 NG/mL, occurring at a mean time of 1.2 hours, weight-normalized, total body clearance was 30% greater, and the elimination half-life 24% shorter in this pediatric population than in adults.
Dedicated pharmacokinetic studies have not been conducted in pediatric patients younger than 6 years of age. A retrospective population pharmacokinetic analysis was conducted in 323 subjects (181 children 1 to 5 years of age, 18 children 6 to 11 years of age, and 124 adults 18 to 55 years of age) who received single or multiple doses of levocetirizine ranging from 1.25 mg to 30 mg. Data generated from this analysis indicated that administration of 1.25 mg once daily to children 6 months to 5 years of age results in plasma concentrations similar to those of adults receiving 5 mg once daily.
Following once daily repeat oral administration of 30 mg levocetirizine for 6 days in 9 elderly subjects (65–74 years of age), the total body clearance was approximately 33% lower compared to that in younger adults. The disposition of race mic satirizing has been shown to be dependent on renal function rather than on age.
Therefore, the Rizal dose should be adjusted in accordance with renal function in elderly patients . Pharmacokinetic results for 77 patients (40 men, 37 women) were evaluated for potential effect of gender.
Fertility and reproductive performance were unaffected in male and female mice and rats that received satirizing at oral doses up to 64 and 200 mg/kg/ day, respectively (approximately 60 and 390 times the MHD in adults on a mg/m2 basis). The efficacy of Rizal was evaluated in four randomized, placebo-controlled, double-blind clinical trials in adult and adolescent patients 12 years and older with symptoms of perennial allergic rhinitis.
These trials included a total of 1729 patients (752 males and 977 females) of whom 227 were adolescents 12 to 17 years of age. The two dose-ranging trials were conducted to evaluate the efficacy of Rizal 2.5, 5, and 10 mg once daily in the evening.
These trials were 4 weeks in duration and included patients with perennial allergic rhinitis. One clinical trial evaluated the efficacy of Rizal 5 mg once daily in the evening compared to placebo in patients with perennial allergic rhinitis over a 6-week treatment period.
Onset of action was also assessed from the daily recording of symptoms in the evening before dosing in the allergic rhinitis trials. There are no clinical efficacy trials with Rizal 2.5 mg once daily in pediatric patients under 12 years of age, and no clinical efficacy trials with Rizal 1.25 mg once daily in pediatric patients 6 months to 5 years of age.
The efficacy of Rizal for the treatment of the uncomplicated skin manifestations of chronic idiopathic urticaria was evaluated in two multi-center, randomized, placebo-controlled, double-blind clinical trials of 4 weeks duration in adult patients 18 to 85 years of age with chronic idiopathic urticaria. The primary efficacy endpoint was the mean reflective pruritic severity score over the first week and over the entire treatment period.
The dose-ranging trial was conducted to evaluate the efficacy of Rizal 2.5, 5, and 10 mg once daily in the evening. The single dose level trial evaluated the efficacy of Rizal 5 mg once daily in the evening compared to placebo in patients with chronic idiopathic urticaria over a 4-week treatment period.
The significant improvement in the instantaneous pruritic severity score over placebo confirmed end of dosing interval efficacy (see Table 6). Rizal oral solution is a clear, colorless liquid containing 0.5 mg of levocetirizine hydrochloride per mL.
Instruct patients to avoid concurrent use of Rizal with alcohol or other central nervous system depressants because additional reduction in mental alertness may occur. In children 6 to 11 years of age the recommended dose is 2.5 mg once daily in the evening.