CLARINEX (desloratadine) Tablets are light blue, round, film coated tablets containing 5 mg deslorata-dine, an antihistamine, to be administered orally. It also contains the following excipients: dibasic calcium phosphate dihydrate USP, microcrystalline cellulose NF, corn starch NF, talc USP, carnauba wax NF, white wax NF, coating material consisting of lactose monohydrate, hydroxypropyl methylcellulose, titanium dioxide, polyethylene glycol, and FD&C Blue #2 Aluminum Lake.

CLARINEX Syrup is a clear orange colored liquid containing 0.5 mg/1mL desloratadine. The syrup contains the following inactive ingredients: propylene glycol USP, sorbitol solution USP, citric acid (anhydrous) USP, sodium citrate dihydrate USP, sodium benzoate NF, disodium edetate USP, purified water USP. It also contains granulated sugar, natural and artificial flavor for bubble gum and FDC Yellow #6 dye.

The CLARINEX RediTabs^® brand of desloratadine orally-disintegrating tablets is a pink colored round tablet shaped units with a "C" debossed on one side. Each RediTabs unit contains 5 mg of desloratadine. It also contains the following inactive ingredients: gelatin Type B NF, mannitol USP, aspartame NF, polarcrillin potassium NF, citric acid USP, red dye and tutti frutti flavoring.

Desloratadine is a white to off-white powder that is slightly soluble in water, but very soluble in ethanol and propylene glycol. It has an empirical formula: C₁₉H₁₉ClN₂ and a molecular weight of 310.8. The chemical name is 8-chloro-6,11- dihydro-11-(4-piperdinylidene)-5H-benzo[5,6]cyclohepta[1,2-b]pyridine and has the following structure:

CLARINEX is indicated for the relief of the nasal and non-nasal symptoms of seasonal allergic rhinitis in patients 2 years of age and older.

CLARINEX is indicated for the relief of the nasal and non-nasal symptoms of perennial allergic rhinitis in patients 6 months of age and older.

CLARINEX is indicated for the symptomatic relief of pruritus, reduction in the number of hives, and size of hives, in patients with chronic idiopathic urticaria 6 months of age and older.

Adults and children 12 years of age and over the recommended dose of CLARINEX Tablets or CLARINEX RediTabs Tablets is one 5 mg tablet once daily or the recommended dose of CLARINEX Syrup is 2 teaspoonfuls (5 mg in 10 mL) once daily.

Children 6 to 11 years of age The recommended dose of CLARINEX Syrup is 1 teaspoonful (2.5 mg in 5 mL) once daily.

Children 12 months to 5 years of age The recommended dose of CLARINEX Syrup is ¹/₂ teaspoonful (1.25 mg in 2.5 mL) once daily.

Children 6 to 11 months of age The recommended dose of CLARINEX Syrup is 2 mL (1.0 mg) once daily.

The age-appropriate dose of CLARINEX Syrup should be administered with a commercially available measuring dropper or syringe that is calibrated to deliver 2 mL and 2.5 mL (¹/₂ teaspoon).

In adult patients with liver or renal impairment, a starting dose of one 5 mg tablet every other day is recommended based on pharmacokinetic data. Dosing recommendation for children with liver or renal impairment cannot be made due to lack of data.

Place CLARINEX (desloratadine) RediTabs Tablets on the tongue. Tablet disintegration occurs rapidly. Administer with or without water. Take tablet immediately after opening the blister.

Embossed "C5", light blue film coated tablets; that are packaged in high-density polyethylene plastic bottles of 100 (NDC 0085-1264-01) and 500 (NDC 0085-1264-02). Also available, CLARINEX Unit-of-Use package of 30 tablets (3 x 10; 10 blisters per card) (NDC 0085-1264-04); and Unit Dose-Hospital Pack of 100 Tablets (10 x 10; 10 blisters per card) (NDC 0085-1264-03).

CLARINEX Syrup clear orange colored liquid containing 0.5 mg/1mL desloratadine in a 16-ounce Amber glass bottle (NDC 0085-1334-01).

CLARINEX REDITABS (desloratadine orally-disintegrating tablets) 5 mg: "C" debossed, pink tablets in foil/foil blisters. Packs of 30 tablets (containing 3 x 10s) NDC 0085-1280-01.

Schering Corporation Kenilworth, NJ 07033 USA, Rev. 8/04, 23882167T, CLARINEX REDITABS brand of desloratadine orally-disintegrating tablets are manufactured for Schering Corporation by Cardinal Health UK. 416 Limited, England. U.S. Patent Nos. 4,659,716; 4,804,666; 4,863,931; 5,595,997; and 6,100,274 Copyright © 2004, Schering Corporation. All rights reserved.

In multiple-dose placebo-controlled trials, 2,834 patients ages 12 years or older received CLARINEX Tablets at doses of 2.5 mg to 20 mg daily, of whom 1,655 patients received the recommended daily dose of 5 mg. In patients receiving 5 mg daily, the rate of adverse events was similar between CLARINEX and placebo-treated patients. The percent of patients who withdrew prematurely due to adverse events was 2.4% in the CLARINEX group and 2.6% in the placebo group. There were no serious adverse events in these trials in patients receiving desloratadine. All adverse events that were reported by greater than or equal to 2% of patients who received the recommended daily dose of CLARINEX Tablets (5.0 mg once-daily), and that were more common with CLARINEX Tablets than placebo, are listed in Table 5.

The frequency and magnitude of laboratory and electrocardiographic abnormalities were similar in CLARINEX and placebo-treated patients.

There were no differences in adverse events for subgroups of patients as defined by gender, age, or race.

In multiple-dose, placebo-controlled trials of chronic idiopathic urticaria, 211 patients ages 12 years or older received CLARINEX Tablets and 205 received placebo. Adverse events that were reported by greater than or equal to 2% of patients who received CLARINEX Tablets and that were more common with CLARINEX than placebo were (rates for CLARINEX and placebo, respectively): headache (14%, 13%), nausea (5%, 2%), fatigue (5%, 1%), dizziness (4%, 3%), pharyngitis (3%, 2%), dyspepsia (3%, 1%), and myalgia (3%, 1%).

Two hundred and forty-six pediatric subjects 6 months to 11 years of age received CLARINEX Syrup for 15 days in three placebo-controlled clinical trials. Pediatric subjects aged 6 to 11 years received 2.5 mg once a day, subjects aged 1 to 5 years received 1.25 mg once a day, and subjects 6 to 11 months of age received 1.0 mg once a day. In subjects 6 to 11 years of age, no individual adverse event was reported by 2 percent or more of the subjects. In subjects 2 to 5 years of age, adverse events reported for CLARINEX and placebo in at least 2 percent of subjects receiving CLARINEX Syrup and at a frequency greater than placebo were fever (5.5%, 5.4%), urinary tract infection (3.6%, 0%) and varicella (3.6%, 0%). In subjects 12 months to 23 months of age, adverse events reported for the CLARINEX product and placebo in at least 2 percent of subjects receiving CLARINEX Syrup and at a frequency greater than placebo were fever (16.9%, 12.9%), diarrhea (15.4% 11.3%), upper respiratory tract infections (10.8%, 9.7%), coughing (10.8%, 6.5%), appetite increased ( 3.1%, 1.6%), emotional lability (3.1%, 0%), epistaxis (3.1%, 0%), parasitic infection, (3.1%, 0%) pharyngitis (3.1%, 0%), rash maculopapular (3.1%, 0%). In subjects 6 months to 11 months of age, adverse events reported for CLARINEX and placebo in at least 2 percent of subjects receiving CLARINEX Syrup and at a frequency greater than placebo were upper respiratory tract infections (21.2%, 12.9%), diarrhea (19.7.% 8.1%), fever (12.1%, 1.6%), irritability (12.1%, 11.3%) coughing (10.6%, 9.7%), somnolence (9.1%, 8.1%), bronchitis (6.1%, 0%), otitis media (6.1%, 1.6%), vomiting (6.1%, 3.2%), anorexia (4.5%, 1.6%), pharyngitis (4.5%, 1.6%), insomnia (4.5%, 0%), rhinorrhea (4.5%, 3.2%), erythema (3.0%, 1.6%), and nausea (3.0%, 0%). There were no clinically meaningful changes in any electrocardiographic parameter, including the QTc interval. Only one of the 246 pediatric subjects receiving CLARINEX Syrup in the clinical trials discontinued treatment because of an adverse event.

The following spontaneous adverse events have been reported during the marketing of desloratadine: tachycardia, palpitations and rarely hypersensitivity reactions (such as rash, pruritus, urticaria, edema, dyspnea, and anaphylaxis), and elevated liver enzymes including bilirubin.

There is no information to indicate that abuse or dependency occurs with CLARINEX Tablets.

In two controlled crossover clinical pharmacology studies in healthy male (n=12 in each study) a nd female (n=12 in each study) volunteers, desloratadine 7.5 mg (1.5 times the daily dose) once daily was coadministered with erythromycin 500 mg every 8 hours or ketoconazole 200 mg every 12 hours for 10 days. In three separate controlled, parallel group clinical pharmacology studies, desloratadine at the clinical dose of 5 mg has been coadministered with azithromycin 500 mg followed by 250 mg once daily for 4 days (n=18) or with fluoxetine 20 mg once daily for 7 days after a 23 day pretreatment period with fluoxetine (n=18) or with cimetidine 600 mg every 12 hours for 14 days (n=18) under steady state conditions to normal healthy male and female volunteers. Although increased plasma concentrations (C _max and AUC 0-24 hrs) of desloratadine and 3-hydroxydesloratadine were observed (see Table 1), there were no clinically relevant changes in the safety profile of desloratadine, as assessed by electrocardiographic parameters (including the corrected QT interval), clinical laboratory tests, vital signs, and adverse events.

No information available.

The carcinogenic potential of desloratadine was assessed using loratadine studies. In an 18-month study in mice and a 2-year study in rats, loratadine was administered in the diet at doses up to 40 mg/kg/day in mice (estimated desloratadine and desloratadine metabolite exposures were approximately 3 times the AUC in humans at the recommended daily oral dose) and 25 mg/kg/day in rats (estimated desloratadine and desloratadine metabolite exposures were approximately 30 times the AUC in humans at the recommended daily oral dose). Male mice given 40 mg/kg/day loratadine had a significantly higher incidence of hepato-cellular tumors (combined adenomas and carcinomas) than concurrent controls. In rats, a significantly higher incidence of hepatocellular tumors (combined adenomas and carcinomas) was observed in males given 10 mg/kg/day and in males and females given 25 mg/kg/day. The estimated desloratadine and desloratadine metabolite exposures of rats given 10 mg/kg of loratadine were approximately 7 times the AUC in humans at the recommended daily oral dose. The clinical significance of these findings during long-term use of desloratadine is not known. In genotoxicity studies with desloratadine, there was no evidence of genotoxic potential in a reverse mutation assay (Salmonella/E. coli mammalian microsome bacterial mutagenicity assay) or in two assays for chromosomal aberrations (human peripheral blood lymphocyte clastogenicity assay and mouse bone marrow micronucleus assay).

There was no effect on female fertility in rats at desloratadine doses up to 24 mg/kg/day (estimated desloratadine and desloratadine metabolite exposures were approximately 130 times the AUC in humans at the recommended daily oral dose). A male specific decrease in fertility, demonstrated by reduced female conception rates, decreased sperm numbers and motility, and histopathologic testicular changes, occurred at an oral desloratadine dose of 12 mg/kg in rats (estimated desloratadine exposures were approximately 45 times the AUC in humans at the recommended daily oral dose). Desloratadine had no effect on fertility in rats at an oral dose of 3 mg/kg/day (estimated desloratadine and desloratadine metabolite exposures were approximately 8 times the AUC in humans at the recommended daily oral dose).

Desloratadine was not teratogenic in rats at doses up to 48 mg/kg/day (estimated deslorata-dine and desloratadine metabolite exposures were approximately 210 times the AUC in humans at the recommended daily oral dose) or in rabbits at doses up to 60 mg/kg/day (estimated desloratadine exposures were approximately 230 times the AUC in humans at the recommended daily oral dose). In a separate study, an increase in pre-implantation loss and a decreased number of implantations and fetuses were noted in female rats at 24 mg/kg (estimated desloratadine and desloratadine metabolite exposures were approximately 120 times the AUC in humans at the recommended daily oral dose). Reduced body weight and slow righting reflex were reported in pups at doses of 9 mg/kg/day or greater (estimated desloratadine and desloratadine metabolite exposures were approximately 50 times or greater than the AUC in humans at the recommended daily oral dose). Desloratadine had no effect on pup development at an oral dose of 3 mg/kg/day (estimated desloratadine and desloratadine metabolite exposures were approximately 7 times the AUC in humans at the recommended daily oral dose). There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, desloratadine should be used during pregnancy only if clearly needed.

Desloratadine passes into breast milk, therefore a decision should be made whether to discontinue nursing or to discontinue desloratadine, taking into account the importance of the drug to the mother.

The recommended dose of CLARINEX Syrup in the pediatric population is based on cross-study comparison of the plasma concentration of CLARINEX in adults and pediatric subjects. The safety of CLARINEX Syrup has been established in 246 pediatric subjects aged 6 months to 11 years in three placebo-controlled clinical studies. Since the course of seasonal and perennial allergic rhinitis and chronic idiopathic urticaria and the effects of CLARINEX are sufficiently similar in the pediatric and adult populations, it allows extrapolation from the adult efficacy data to pediatric patients. The effectiveness of CLARINEX Syrup in these age groups is supported by evidence from adequate and well-controlled studies of CLARINEX Tablets in adults. The safety and effectiveness of CLARINEX Tablets or CLARINEX Syrup have not been demonstrated in pediatric patients less than 6 months of age.

Clinical studies of desloratadine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy (see CLINICAL PHARMACOLOGY Special Populations).

Information regarding acute overdosage is limited to experience from clinical trials conducted during the development of the CLARINEX product. In a dose ranging trial, at doses of 10 mg and 20 mg/day somnolence was reported.

Single daily doses of 45 mg were given to normal male and female volunteers for 10 days. All ECGs obtained in this study were manually read in a blinded fashion by a cardiologist. In CLARINEX-treated subjects, there was an increase in mean heart rate of 9.2 bpm relative to placebo. The QT interval was corrected for heart rate (QTc) by both the Bazett and Fridericia methods. Using the QTc (Bazett) there was a mean increase of 8.1 msec in CLARINEX-treated subjects relative to placebo. Using QTc (Fridericia) there was a mean increase of 0.4 msec in CLARINEX-treated subjects relative to placebo. No clinically relevant adverse events were reported.

In the event of overdose, consider standard measures to remove any unabsorbed drug. Symptomatic and supportive treatment is recommended. Desloratadine and 3-hydroxydesloratadine are not eliminated by hemodialysis.

Lethality occurred in rats at oral doses of 250 mg/kg or greater (estimated desloratadine and desloratadine metabolite exposures were approximately 120 times the AUC in humans at the recommended daily oral dose). The oral median lethal dose in mice was 353 mg/kg (estimated desloratadine exposures were approximately 290 times the human daily oral dose on a mg/m² basis). No deaths occurred at oral doses up to 250 mg/kg in monkeys (estimated desloratadine exposures were approximately 810 times the human daily oral dose on a mg/m² basis).

CLARINEX Tablets 5 mg are contraindicated in patients who are hypersensitive to this medication or to any of its ingredients, or to loratadine.

Desloratadine is a long-acting tricyclic histamine antagonist with selective H₁-receptor histamine antagonist activity. Receptor binding data indicates that at a concentration of 2-3 ng/mL (7 nanomolar), desloratadine shows significant interaction with the human histamine H₁- receptor. Desloratadine inhibited histamine release from human mast cells in vitro.

Results of a radiolabeled tissue distribution study in rats and a radioligand H₁-receptor binding study in guinea pigs showed that desloratadine did not readily cross the blood brain barrier.

Following oral administration of desloratadine 5 mg once daily for 10 days to normal healthy volunteers, the mean time to maximum plasma concentrations (T_max) occurred at approximately 3 hours post dose and mean steady state peak plasma concentrations (C_max) and area under the concentration-time curve (AUC) of 4 ng/mL and 56.9 ng.hr/mL were observed, respectively. Neither food nor grapefruit juice had an effect on the bioavailability (C_max and AUC) of desloratadine.

The pharmacokinetic profile of CLARINEX Syrup was evaluated in a three-way crossover study in 30 adult volunteers. A single dose of 10 mL of CLARINEX Syrup containing 5 mg of desloratadine was bioequivalent to a single dose of 5 mg CLARINEX Tablet. Food had no effect on the bioavailability (AUC and C_max) of CLARINEX Syrup.

The pharmacokinetic profile of CLARINEX RediTabs Tablets was evaluated in a three-way crossover study in 30 adult volunteers. A single CLARINEX RediTabs Tablet containing 5 mg of desloratadine was bioequivalent to a single 5 mg CLARINEX Tablet and was bioequivalent to 10 mL of CLARINEX Syrup containing 5 mg of desloratadine for both deslor-atadine and 3-hydroxydesloratadine. In a separate study with 30 adult volunteers, food or water had no effect on the bioavailability (AUC and C_max) of CLARINEX RediTabs Tablets, however, food shifted the desloratadine median T_max value from 2.5 to 4 hr.

Desloratadine and 3-hydroxydesloratadine are approximately 82% to 87% and 85% to 89%, bound to plasma proteins, respectively. Protein binding of desloratadine and 3-hydroxydesloratadine was unaltered in subjects with impaired renal function.

Desloratadine (a major metabolite of loratadine) is extensively metabolized to 3-hydroxydesloratadine, an active metabolite, which is subsequently glucuronidated. The enzyme(s) responsible for the formation of 3-hydroxy-desloratadine have not been identified. Data from clinical trials indicate that a subset of the general population has a decreased ability to form 3-hydroxydesloratadine, and are poor metabolizers of desloratadine. In pharmacokinetic studies (n= 3748), approximately 6% of subjects were poor metabolizers of desloratadine (defined as a subject with an AUC ratio of 3-hydroxydesloratadine to desloratadine less than 0.1, or a subject with a desloratadine half-life exceeding 50 hours). These pharmacokinetic studies included subjects between the ages of 2 and 70 years, including 977 subjects aged 2-5 years, 1575 subjects aged 6-11 years, and 1196 subjects aged 12-70 years. There was no difference in the prevalence of poor metabolizers across age groups. The frequency of poor metabolizers was higher in Blacks (17%, n=988) as compared to Caucasians (2%, n=1462) and Hispanics (2%, n=1063). The median exposure (AUC) to deslor-atadine in the poor metabolizers was approximately 6-fold greater than in the subjects who are not poor metabolizers. Subjects who are poor metabolizers of desloratadine cannot be prospectively identified and will be exposed to higher levels of desloratadine following dosing with the recommended dose of desloratadine. In multidose clinical safety studies, where metabolizer status was identified, a total of 94 poor metabolizers and 123 normal metabolizers were enrolled and treated with CLARINEX for 15-35 days. In these studies, no overall differences in safety were observed between poor metabolizers and normal metabolizers. Although not seen in these studies, an increased risk of exposure-related adverse events in patients who are poor metabolizers cannot be ruled out.

The mean elimination half-life of desloratadine was 27 hours. C_max and AUC values increased in a dose proportional manner following single oral doses between 5 and 20 mg. The degree of accumulation after 14 days of dosing was consistent with the half-life and dosing frequency. A human mass balance study documented a recovery of approximately 87% of the ¹⁴C-desloratadine dose, which was equally distributed in urine and feces as metabolic products. Analysis of plasma 3-hydroxydesloratadine showed similar T_max and half-life values compared to desloratadine.

In older subjects (≥γ 65 years old; n=17) following multiple-dose administration of CLARINEX Tablets, the mean C_max and AUC values for desloratadine were 20% greater than in younger subjects (< 65 years old). The oral total body clearance (CL/F) when normalized for body weight was similar between the two age groups. The mean plasma elimination half-life of desloratadine was 33.7 hr in subjects ≥65 years old. The pharmacoki-netics for 3-hydroxydesloratadine appeared unchanged in older versus younger subjects. These age-related differences are unlikely to be clinically relevant and no dosage adjustment is recommended in elderly subjects.

In subjects 6 to 11 years old, a single dose of 5 mL of CLARINEX Syrup containing 2.5 mg of desloratadine, resulted in desloratadine plasma concentrations similar to those achieved in adults administered a single 5 mg CLARINEX Tablet. In subjects 2 to 5 years old, a single dose of 2.5 mL of CLARINEX Syrup containing 1.25 mg of desloratadine, resulted in desloratadine plasma concentrations similar to those achieved in adults administered a single 5 mg CLARINEX Tablet. However, the C_max and AUC of the metabolite (3-OH desloratadine) were 1.27 and 1.61 times higher for the 5 mg dose of syrup administered in adults compared to the C_max and AUC obtained in children 2-11 years of age receiving 1.25-2.5 mg of CLARINEX Syrup.

A single dose of either 2.5 mL or 1.25 mL of CLARINEX Syrup containing 1.25 mg or 0.625 mg, respectively, of deslor-atadine was administered to subjects 6 to 11 months of age and 12 to 23 months of age. The results of a population phar-macokinetic analysis indicated that a dose of 1 mg for subjects aged 6 to 11 months and 1.25 mg for subjects 12 to 23 months of age is required to obtain desloratadine plasma concentrations similar to those achieved in adults administered a single 5 mg dose of CLARINEX Syrup.

Desloratadine pharmacokinetics following a single dose of 7.5 mg were characterized in patients with mild (n=7; creatinine clearance 51-69 mL/min/1.73 m²), moderate (n=6; creatinine clearance 34-43 mL/min/1.73 m²), and severe (n=6; creatinine clearance 5-29 mL/min/1.73 m²) renal impairment or hemodialysis dependent (n=6) patients. In patients with mild and moderate renal impairment, median C_max and AUC values increased by approximately 1.2- and 1.9-fold, respectively, relative to subjects with normal renal function. In patients with severe renal impairment or who were hemodialysis dependent, C_max and AUC values increased by approximately 1.7- and 2.5- fold, respectively. Minimal changes in 3-hydroxydesloratadine concentrations were observed. Desloratadine and 3-hydroxydesloratadine were poorly removed by hemodialysis. Plasma protein binding of desloratadine and 3-hydroxy-desloratadine was unaltered by renal impairment. Dosage adjustment for patients with renal impairment is recommended (see DOSAGE AND ADMINISTRATION section).

Desloratadine pharmacokinetics were characterized following a single oral dose in patients with mild (n=4), moderate (n=4), and severe (n=4) hepatic impairment as defined by the Child-Pugh classification of hepatic function and 8 subjects with normal hepatic function. Patients with hepatic impairment, regardless of severity, had approximately a 2.4-fold increase in AUC as compared with normal subjects. The apparent oral clearance of deslorata-dine in patients with mild, moderate, and severe hepatic impairment was 37%, 36%, and 28% of that in normal subjects, respectively. An increase in the mean elimination half-life of desloratadine in patients with hepatic impairment was observed. For 3-hydroxydesloratadine, the mean C_max and AUC values for patients with hepatic impairment were not statistically significantly different from subjects with normal hepatic function. Dosage adjustment for patients with hepatic impairment is recommended (see DOSAGE AND ADMINISTRATION section).

Female subjects treated for 14 days with CLARINEX Tablets had 10% and 3% higher desloratadine C_max and AUC values, respectively, compared with male subjects. The 3-hydroxydesloratadine C_max and AUC values were also increased by 45% and 48%, respectively, in females compared with males. However, these apparent differences are not likely to be clinically relevant and therefore no dosage adjustment is recommended.

Following 14 days of treatment with CLARINEX Tablets, the C_max and AUC values for desloratadine were 18% and 32% higher, respectively, in Blacks compared with Caucasians. For 3-hydroxydesloratadine there was a corresponding 10% reduction in C_max and AUC values in Blacks compared to Caucasians. These differences are not likely to be clinically relevant and therefore no dose adjustment is recommended.

Drug Interactions

In two controlled crossover clinical pharmacology studies in healthy male (n=12 in each study) and female (n=12 in each study) volunteers, desloratadine 7.5 mg (1.5 times the daily dose) once daily was coadministered with erythromycin 500 mg every 8 hours or ketoconazole 200 mg every 12 hours for 10 days. In three separate controlled, parallel group clinical pharmacology studies, desloratadine at the clinical dose of 5 mg has been coadministered with azithromycin 500 mg followed by 250 mg once daily for 4 days (n=18) or with fluoxetine 20 mg once daily for 7 days after a 23 day pretreatment period with fluoxetine (n=18) or with cimetidine 600 mg every 12 hours for 14 days (n=18) under steady state conditions to normal healthy male and female volunteers. Although increased plasma concentrations (C_max and AUC 0-24 hrs) of desloratadine and 3-hydroxydesloratadine were observed (see Table 1), there were no clinically relevant changes in the safety profile of desloratadine, as assessed by electrocardiographic parameters (including the corrected QT interval), clinical laboratory tests, vital signs, and adverse events.

Human histamine skin wheal studies following single and repeated 5 mg doses of desloratadine have shown that the drug exhibits an antihistaminic effect by 1 hour; this activity may persist for as long as 24 hours. There was no evidence of histamine-induced skin wheal tachyphylaxis within the desloratadine 5 mg group over the 28 day treatment period. The clinical relevance of histamine wheal skin testing is unknown.

Single dose administration of desloratadine did not alter the corrected QT interval (QTc) in rats (up to 12 mg/kg, oral), or guinea pigs (25 mg/kg, intravenous). Repeated oral administration at doses up to 24 mg/kg for durations up to 3 months in monkeys did not alter the QT_c at an estimated desloratadine exposure (AUC) that was approximately 955 times the mean AUC in humans at the recommended daily oral dose. See OVERDOSAGE section for information on human QT_c experience.

The clinical efficacy and safety of CLARINEX Tablets were evaluated in over 2,300 patients 12 to 75 years of age with seasonal allergic rhinitis. A total of 1,838 patients received 2.5-20 mg/day of CLARINEX in four double-blind, randomized, placebo-controlled clinical trials of 2 to 4 weeks duration conducted in the United States. The results of these studies demonstrated the efficacy and safety of CLARINEX 5 mg in the treatment of adult and adolescent patients with seasonal allergic rhinitis. In a dose ranging trial, CLARINEX 2.5-20 mg/day was studied. Doses of 5, 7.5, 10, and 20 mg/day were superior to placebo; and no additional benefit was seen at doses above 5.0 mg. In the same study, an increase in the incidence of somnolence was observed at doses of 10 mg/day and 20 mg/day (5.2% and 7.6%, respectively), compared to placebo (2.3%).

In two 4-week studies of 924 patients (aged 15 to 75 years) with seasonal allergic rhinitis and concomitant asthma, CLARINEX Tablets 5 mg once daily improved rhinitis symptoms, with no decrease in pulmonary function. This supports the safety of administering CLARINEX Tablets to adult patients with seasonal allergic rhinitis with mild to moderate asthma.

CLARINEX Tablets 5 mg once daily significantly reduced the Total Symptom Scores (the sum of individual scores of nasal and non-nasal symptoms) in patients with seasonal allergic rhinitis. See Table 2.

There were no significant differences in the effectiveness of CLARINEX Tablets 5 mg across subgroups of patients defined by gender, age, or race.

The clinical efficacy and safety of CLARINEX Tablets 5 mg were evaluated in over 1,300 patients 12 to 80 years of age with perennial allergic rhinitis. A total of 685 patients received 5 mg/day of CLARINEX in two double-blind, randomized, placebo-controlled clinical trials of 4 weeks duration conducted in the United States and internationally. In one of these studies CLARINEX Tablets 5 mg once daily was shown to significantly reduce symptoms of perennial allergic rhinitis (Table 3).

The efficacy and safety of CLARINEX Tablets 5 mg once daily was studied in 416 chronic idiopathic urticaria patients 12 to 84 years of age, of whom 211 received CLARINEX. In two double-blind, placebo-controlled, randomized clinical trials of six weeks duration, at the pre-specified one-week primary time point evaluation, CLARINEX Tablets significantly reduced the severity of pruritus when compared to placebo (Table 4). Secondary endpoints were also evaluated and during the first week of therapy CLARINEX Tablets 5 mg reduced the secondary endpoints, "Number of Hives" and the "Size of the Largest Hive," when compared to placebo.

The clinical safety of CLARINEX Syrup was documented in three, 15-day, double-blind, placebo-controlled safety studies in pediatric subjects with a documented history of allergic rhinitis, chronic idiopathic urticaria, or subjects who were candidates for antihistamine therapy. In the first study, 2.5 mg of CLARINEX Syrup was administered to 60 pediatric subjects 6 to 11 years of age. The second study evaluated 1.25 mg of CLARINEX Syrup administered to 55 pediatric subjects 2 to 5 years of age. In the third study, 1.25 mg of CLARINEX Syrup was administered to 65 pediatric subjects 12 to 23 months of age and 1.0 mg of CLARINEX Syrup was administered to 66 pediatric subjects 6 to 11 months of age. The results of these studies demonstrated the safety of CLARINEX Syrup in pediatric subjects 6 months to 11 years of age.

Patients should be instructed to use CLARINEX Tablets as directed. As there are no food effects on bioavailability, patients can be instructed that CLARINEX Tablets may be taken without regard to meals. Patients should be advised not to increase the dose or dosing frequency as studies have not demonstrated increased effectiveness at higher doses and somnolence may occur. Phenylketonurics: CLARINEX RediTabs Tablets contain phenylalanine 1.75 mg per tablet.

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

DESLORATADINE - ORAL

(des-lor-AT-uh-deen)

COMMON BRAND NAME(S): Clarinex

USES: Desloratadine is an antihistamine that provides relief of seasonal allergy symptoms and allergic nasal conditions (rhinitis) such as runny nose, sneezing, and watery/itching eyes. It may also be used to treat hives.

HOW TO USE: Take this medication by mouth once a day or as directed by your doctor.

Do not increase your dose or take this more often than directed.

Do not take this medication for several days before allergy testing since test results may be affected.

Inform your doctor if your condition persists or worsens.

SIDE EFFECTS: Throat discomfort, muscle pain, nausea, indigestion, loss of appetite, diarrhea, dizziness, fatigue, trouble sleeping, nosebleeds, or dry mouth may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

Desloratadine does not usually cause drowsiness when used at recommended doses and under normal circumstances. However, be sure of the drug's effects before engaging in activities that require alertness such as driving or using machinery.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if this unlikely but serious side effect occurs: rapid or pounding heartbeat.

Tell your doctor immediately if any of these rare but very serious side effects occurs: dark urine, yellowing eyes or skin.

A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction may include: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking desloratadine, tell your doctor or pharmacist if you are allergic to it; or to loratadine; or if you have any other allergies.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney disease, liver disease.

Limit alcohol intake, as it may intensify drug side effects.

Desloratadine should be used only when clearly needed during pregnancy. Discuss the risks and benefits with your doctor.

This medication passes into breast milk. Breast-feeding is not recommended while using this drug.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with them first.

Before using this medication, tell your doctor or pharmacist of any prescription or nonprescription medication you may take.

Check the labels on all your medicines (e.g., cough-and-cold products) because they may contain additional antihistamines that could increase your risk for side effects. Ask your pharmacist about the safe use of those products.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canadian residents should call their local poison control center directly. Symptoms of overdose may include drowsiness or fast heartbeat.

NOTES: Do not share this medication with others.

MISSED DOSE: If you miss a dose, take it as soon as remembered; do not take it near the time for the next dose, instead, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store between 36-77 degrees F (2-25 degrees C) away from light and moisture. Do not store in bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.