relevant changes in the safety profile of desloratadine. [see clinical pharmacology (12.3) .]

as desloratadine syrup is better suited for these patients. 2.5 adults with hepatic or renal impairment 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 [see clinical pharmacology (12.3) ].

ine 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 desloratadine and placebo-treated patients. the percent of patients who withdrew prematurely due to adverse events was 2.4% in the desloratadine 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 desloratadine tablets (5 mg once daily), and that were more common with desloratadine tablets than placebo, are listed in table 1. table 1 incidence of adverse events reported by ≥2% of adult and adolescent allergic rhinitis patients receiving desloratadine tablets adverse event desloratadine tablets 5 mg (n=1655) placebo (n=1652) infections and infestations pharyngitis 4.1% 2.0% nervous system disorders somnolence 2.1% 1.8% gastrointestinal disorders dry mouth 3.0% 1.9% musculoskeletal and connective tissue disorders myalgia 2.1% 1.8% reproductive system and breast disorders dysmenorrhea 2.1% 1.6% general disorders and administration site conditions fatigue 2.1% 1.2% the frequency and magnitude of laboratory and electrocardiographic abnormalities were similar in desloratadine and placebo-treated patients. there were no differences in adverse events for subgrous of patients as defined by gender, age, or race. pediatrics two hundred and forty-six pediatric subjects 6 months to 11 years of age received desloratadine 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 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 desloratadine and placebo in at least 2 percent of subjects receiving desloratadine 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 desloratadine product and placebo in at least 2 percent of subjects receiving desloratadine 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 desloratadine and placebo in at least 2 percent of subjects receiving desloratadine 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%, 1.6%), and nausea (3%, 0%). there were no clinically meaningful changes in any electrocardiographic parameter, including the qtc interval. only one of the 246 pediatric subjects receiving desloratadine in the clinical trials discontinued treatment because of an adverse event. 6.2 post-marketing experience because adverse 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. the following spontaneous adverse events have been reported during the marketing of desloratadine: cardiac disorders : tachycardia, palpitations respiratory, thoracic and mediastinal disorders : dyspnea skin and subcutaneous tissue disorders : rash, pruritus nervous system disorders : psychomotor hyperactivity, movement disorders (including dystonia, tics, and extrapyramidal symptoms), seizures (reported in patients with and without a known seizure disorder) immune system disorders : hypersensitivity reactions (such as urticaria, edema and anaphylaxis) investigations : elevated liver enzymes including bilirubin hepatobiliary disorders : hepatitis metabolism and nutrition disorders : increased appetite

relevant changes in the safety profile of desloratadine. [see clinical pharmacology (12.3) .]

reflex of f 1 pups at the summed auc-based exposures of desloratadine and its metabolite approximately 70 times or greater than that at the rhd [see data]. the estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. data animal data desloratadine was given orally during organogenesis to pregnant rats at doses of 6, 24 and 48 mg/kg/day (approximately 50, 200 and 320 times the summed auc-based exposure of desloratadine and its metabolite at the rhd). no fetal malformations were present. reduced fetal weights and skeletal variations noted at doses of 24 and 48 mg/kg/day were likely secondary to the maternal toxicities of reduced body weight gain and food consumption observed at the same doses. desloratadine was also given orally during organogenesis to pregnant rabbits at doses of 15, 30 and 60 mg/kg/day (approximately 30, 70 and 230 times the auc-based exposure of desloratadine at the rhd). no adverse effects to the fetus were noted. reduced maternal body weight gain was noted in rabbits at 60 mg/kg/day. in a peri-and post-natal development study, desloratadine was given to rats orally during the peri-natal (gestation day 6) through lactation periods (postpartum day 21) at doses of 3, 9 and 18 mg/kg/day. reduced body weight and slow righting reflex were reported in f1 pups at doses of 9 mg/kg/day or greater (approximately 70 times or greater than the summed auc-based exposure of desloratadine and its metabolite at the rhd). desloratadine had no effect on f 1 pup development at 3 mg/kg/day (approximately 10 times the summed auc-based exposure of desloratadine and its metabolite at the rhd). maternal toxicities including reduced body weight gain and food consumption were noted at 18 mg/kg/day for f 0 dams. f 1 offspring were subsequently mated and there was no developmental toxicity for f 2 pups observed. 8.2 lactation risk summary desloratadine passes into breast milk. there are not sufficient data on the effects of desloratadine on the breastfed infant or the effects of desloratadine on milk production. the decision should be made whether to discontinue nursing or to discontinue desloratadine, taking into account the developmental and health benefits of breastfeeding, the nursing mother’s clinical need, and any potential adverse effects on the breastfed infant from desloratadine or from the underlying maternal condition. 8.3 females and males of reproductive potential infertility there are no data available on human infertility associated with desloratadine. there were no clinically relevant effects of desloratadine on female fertility in rats. a male specific decrease in fertility occurred at an oral desloratadine dose of 12 mg/kg or greater in rats (approximately 65 times the summed auc-based exposure of desloratadine and its metabolite at the rhd). male fertility was unaffected at a desloratadine dose of 3 mg/kg (approximately 10 times the summed auc-based exposure of desloratadine and its metabolite at the rhd) [see nonclinical toxicology ( 13.1 ).] 8.4 pediatric use the desloratadine orally disintegrating 2.5 mg tablet has not been evaluated in pediatric patients. bioequivalence of the desloratadine orally disintegrating tablet and the previously marketed orally disintegrating tablet was established in adults. in conjunction with the dose-finding studies in pediatrics described, the pharmacokinetic data for desloratadine orally disintegrating tablet supports the use of the 2.5 mg dose strength in pediatric patients 6 to 11 years of age. 8.5 geriatric use 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 identifiied 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 (12.3) ] 8.6 renal impairment dosage adjustment for patients with renal impairment is recommended [see dosage and administration (2.5) and clinical pharmacology (12.3) ]. 8.7 hepatic impairment dosage adjustment for patients with hepatic impairment is recommended [see dosage and administration (2.5) and clinical pharmacology (12.3) ]

ound risk of major birth defects and miscarriage for the indicated populations is unknown. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. data animal data desloratadine was given orally during organogenesis to pregnant rats at doses of 6, 24 and 48 mg/kg/day (approximately 50, 200 and 320 times the summed auc-based exposure of desloratadine and its metabolite at the rhd). no fetal malformations were present. reduced fetal weights and skeletal variations noted at doses of 24 and 48 mg/kg/day were likely secondary to the maternal toxicities of reduced body weight gain and food consumption observed at the same doses. desloratadine was also given orally during organogenesis to pregnant rabbits at doses of 15, 30 and 60 mg/kg/day (approximately 30, 70 and 230 times the auc-based exposure of desloratadine at the rhd). no adverse effects to the fetus were noted. reduced maternal body weight gain was noted in rabbits at 60 mg/kg/day. in a peri-and post-natal development study, desloratadine was given to rats orally during the peri-natal (gestation day 6) through lactation periods (postpartum day 21) at doses of 3, 9 and 18 mg/kg/day. reduced body weight and slow righting reflex were reported in f1 pups at doses of 9 mg/kg/day or greater (approximately 70 times or greater than the summed auc-based exposure of desloratadine and its metabolite at the rhd). desloratadine had no effect on f 1 pup development at 3 mg/kg/day (approximately 10 times the summed auc-based exposure of desloratadine and its metabolite at the rhd). maternal toxicities including reduced body weight gain and food consumption were noted at 18 mg/kg/day for f 0 dams. f 1 offspring were subsequently mated and there was no developmental toxicity for f 2 pups observed.

sloratadine 5 mg group over the 28-day treatment period. the clinical relevance of histamine wheal skin testing is unknown. effects on qt c : 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 desloratadine-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 (qt c ) by both the bazett and fridericia methods. using the qt c (bazett) there was a mean increase of 8.1 msec in desloratadine-treated subjects relative to placebo. using qt c (fridericia) there was a mean increase of 0.4 msec in desloratadine-treated subjects relative to placebo. no clinically relevant adverse events were reported. 12.3 pharmacokinetics absorption the pharmacokinetic profile of desloratadine orally disintegrating tablets was evaluated in a three-way crossover study in 24 adult volunteers. a single desloratadine orally disintegrating tablets containing 5 mg of desloratadine was bioequivalent to a single 5 mg desloratadine orally disintegrating tablets (original formulation) for both desloratadine and 3-hydroxydesloratadine. food and water had no effect on the bioavailability (auc and c max ) of desloratadine orally disintegrating tablets. distribution 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. metabolism 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-hydroxydesloratadine 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 to 5 years, 1,575 subjects aged 6 to 11 years, and 1,196 subjects aged 12 to 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=1,462) and hispanics (2%, n=1,063). the median exposure (auc) to desloratadine 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 desloratadine oral solution for 15 to 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. elimination the mean plasma elimination half-life of desloratadine was approximately 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 14 c-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. special populations geriatric subjects : in older subjects (³65 years old; n=17) following multiple-dose administration of desloratadine 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 ³65 years old. the pharmacokinetics 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. pediatric subjects: in subjects 6 to 11 years old, a single dose of 5 ml of desloratadine oral solution containing 2.5 mg of desloratadine, resulted in desloratadine plasma concentrations similar to those achieved in adults administered a single 5 mg desloratadine tablet. in subjects 2 to 5 years old, a single dose of 2.5 ml of desloratadine oral solution containing 1.25 mg of desloratadine, resulted in desloratadine plasma concentrations similar to those achieved in adults administered a single 5 mg desloratadine tablet. however, the c max and auc of the metabolite (3-hydroxydesloratadine) were 1.27 and 1.61 times higher for the 5 mg dose of oral solution administered in adults compared to the c max and auc obtained in children 2 to 11 years of age receiving 1.25 to 2.5 mg of desloratadine oral solution. a single dose of either 2.5 ml or 1.25 ml of desloratadine oral solution containing 1.25 mg or 0.625 mg, respectively, of desloratadine was administered to subjects 6 to 11 months of age and 12 to 23 months of age. the results of a population pharmacokinetic 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 desloratadine oral solution. the desloratadine orally disintegrating tablet 2.5 mg tablet has not been evaluated in pediatric patients. bioequivalence of the desloratadine orally disintegrating tablet and the original desloratadine orally disintegrating tablet was established in adults. in conjunction with the dose-finding studies in pediatrics described, the pharmacokinetic data for desloratadine orally disintegrating tablets supports the use of the 2.5 mg dose strength in pediatric patients 6 to 11 years of age. renally impaired : desloratadine pharmacokinetics following a single dose of 7.5 mg were characterized in patients with mild (n=7; creatinine clearance 51 to 69 ml/min/1.73 m 2 ), moderate (n=6; creatinine clearance 34 to 43 ml/min/1.73 m 2 ), and severe (n=6; creatinine clearance 5 to 29 ml/min/1.73 m 2 ) 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-hydroxydesloratadine was unaltered by renal impairment. dosage adjustment for patients with renal impairment is recommended [see dosage and administration (2.5) ]. hepatically impaired : 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 desloratadine 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 (2.5) ]. gender : female subjects treated for 14 days with desloratadine 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. race : following 14 days of treatment with desloratadine 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 auc0-24 hrs) of desloratadine and 3-hydroxydesloratadine were observed (see table 2), 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. table 2 changes in desloratadine and 3-hydroxydesloratadine pharmacokinetics in healthy male and female volunteers desloratadine 3-hydroxydesloratadine c max auc 0-24hrs c max auc 0-24hrs erythromycin (500 mg q8h) + 24% + 14% + 43% + 40% ketoconazole (200 mg q12h) + 45% + 39% + 43% + 72% azithromycin (500 mg day 1,250 mg qd x 4 days) + 15% + 5% + 15% + 4% fluoxetine (200 mg qd) + 15% + 0% + 17% + 13% cimetidine (600 mg q12h) + 12% + 19% - 11% - 3%

tion of 3-hydroxydesloratadine 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 to 5 years, 1,575 subjects aged 6 to 11 years, and 1,196 subjects aged 12 to 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=1,462) and hispanics (2%, n=1,063). the median exposure (auc) to desloratadine 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 desloratadine oral solution for 15 to 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. elimination the mean plasma elimination half-life of desloratadine was approximately 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 14 c-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. special populations geriatric subjects : in older subjects (³65 years old; n=17) following multiple-dose administration of desloratadine 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 ³65 years old. the pharmacokinetics 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. pediatric subjects: in subjects 6 to 11 years old, a single dose of 5 ml of desloratadine oral solution containing 2.5 mg of desloratadine, resulted in desloratadine plasma concentrations similar to those achieved in adults administered a single 5 mg desloratadine tablet. in subjects 2 to 5 years old, a single dose of 2.5 ml of desloratadine oral solution containing 1.25 mg of desloratadine, resulted in desloratadine plasma concentrations similar to those achieved in adults administered a single 5 mg desloratadine tablet. however, the c max and auc of the metabolite (3-hydroxydesloratadine) were 1.27 and 1.61 times higher for the 5 mg dose of oral solution administered in adults compared to the c max and auc obtained in children 2 to 11 years of age receiving 1.25 to 2.5 mg of desloratadine oral solution. a single dose of either 2.5 ml or 1.25 ml of desloratadine oral solution containing 1.25 mg or 0.625 mg, respectively, of desloratadine was administered to subjects 6 to 11 months of age and 12 to 23 months of age. the results of a population pharmacokinetic 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 desloratadine oral solution. the desloratadine orally disintegrating tablet 2.5 mg tablet has not been evaluated in pediatric patients. bioequivalence of the desloratadine orally disintegrating tablet and the original desloratadine orally disintegrating tablet was established in adults. in conjunction with the dose-finding studies in pediatrics described, the pharmacokinetic data for desloratadine orally disintegrating tablets supports the use of the 2.5 mg dose strength in pediatric patients 6 to 11 years of age. renally impaired : desloratadine pharmacokinetics following a single dose of 7.5 mg were characterized in patients with mild (n=7; creatinine clearance 51 to 69 ml/min/1.73 m 2 ), moderate (n=6; creatinine clearance 34 to 43 ml/min/1.73 m 2 ), and severe (n=6; creatinine clearance 5 to 29 ml/min/1.73 m 2 ) 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-hydroxydesloratadine was unaltered by renal impairment. dosage adjustment for patients with renal impairment is recommended [see dosage and administration (2.5) ]. hepatically impaired : 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 desloratadine 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 (2.5) ]. gender : female subjects treated for 14 days with desloratadine 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. race : following 14 days of treatment with desloratadine 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 auc0-24 hrs) of desloratadine and 3-hydroxydesloratadine were observed (see table 2), 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. table 2 changes in desloratadine and 3-hydroxydesloratadine pharmacokinetics in healthy male and female volunteers desloratadine 3-hydroxydesloratadine c max auc 0-24hrs c max auc 0-24hrs erythromycin (500 mg q8h) + 24% + 14% + 43% + 40% ketoconazole (200 mg q12h) + 45% + 39% + 43% + 72% azithromycin (500 mg day 1,250 mg qd x 4 days) + 15% + 5% + 15% + 4% fluoxetine (200 mg qd) + 15% + 0% + 17% + 13% cimetidine (600 mg q12h) + 12% + 19% - 11% - 3%

auc-based exposure of desloratadine and its metabolite at the rhd, respectively), did not show significant increases in the incidence of any tumors. genotoxicity studies 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 2 assays for chromosomal aberrations (human peripheral blood lymphocyte clastogenicity assay and mouse bone marrow micronucleus assay). impairment of fertility in a female fertility study, desloratadine was given to female rats orally 14 days prior to and throughout mating until gestation day 7 at doses of 6, 12 and 24 mg/kg/day. an increase in preimplantation loss and a decrease in number of implantations and fetuses noted at 24 mg/kg (approximately 200 times the summed auc-based exposure of desloratadine and its metabolite at the rhd) was likely due to maternal toxicities including reduced body weight gain and food consumption. in a male fertility study in rats, desloratadine was given orally to male rats for 70 days prior to mating and throughout the mating period (total dosing period 106 to 108 days) at doses of 3, 12 and 40 mg/kg/day. reduced body weight gain, food consumption, and absolute organ weights of testes, epididymis, and cauda epididymis were noted at 40 mg/kg/day. a male-specific decrease in fertility, demonstrated by reduced female conception rates, decreased sperm numbers and motility, and histopathologic changes in testes and epididymis, occurred at a dose of 12 mg/kg or greater (approximately 65 times or greater than the summed auc-based exposure of desloratadine and its metabolite at the rhd). desloratadine had no effect on male fertility in rats at 3 mg/kg/day (approximately 10 times the summed auc-based exposure of desloratadine and its metabolite at the rhd).

loratadine and its metabolite at the rhd, respectively), did not show significant increases in the incidence of any tumors. genotoxicity studies 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 2 assays for chromosomal aberrations (human peripheral blood lymphocyte clastogenicity assay and mouse bone marrow micronucleus assay). impairment of fertility in a female fertility study, desloratadine was given to female rats orally 14 days prior to and throughout mating until gestation day 7 at doses of 6, 12 and 24 mg/kg/day. an increase in preimplantation loss and a decrease in number of implantations and fetuses noted at 24 mg/kg (approximately 200 times the summed auc-based exposure of desloratadine and its metabolite at the rhd) was likely due to maternal toxicities including reduced body weight gain and food consumption. in a male fertility study in rats, desloratadine was given orally to male rats for 70 days prior to mating and throughout the mating period (total dosing period 106 to 108 days) at doses of 3, 12 and 40 mg/kg/day. reduced body weight gain, food consumption, and absolute organ weights of testes, epididymis, and cauda epididymis were noted at 40 mg/kg/day. a male-specific decrease in fertility, demonstrated by reduced female conception rates, decreased sperm numbers and motility, and histopathologic changes in testes and epididymis, occurred at a dose of 12 mg/kg or greater (approximately 65 times or greater than the summed auc-based exposure of desloratadine and its metabolite at the rhd). desloratadine had no effect on male fertility in rats at 3 mg/kg/day (approximately 10 times the summed auc-based exposure of desloratadine and its metabolite at the rhd).

nal allergic rhinitis and concomitant asthma, desloratadine tablets 5 mg once daily improved rhinitis symptoms, with no decrease in pulmonary function. this supports the safety of administering desloratadine tablets to adult patients with seasonal allergic rhinitis with mild to moderate asthma. desloratadine tablets 5 mg once daily significantly reduced the total symptom score (the sum of individual scores of nasal and non-nasal symptoms) in patients with seasonal allergic rhinitis. see table 3. table 3 total symptom score (tss) changes in a 2 week clinical trial in patients with seasonal allergic rhinitis treatment group (n) mean baseline* (sem) change from baseline** (sem) placebo comparison (p-value) desloratadine 5 mg (171) 14.2 (0.3) -4.3 (0.3) p<0.01 placebo (173) 13.7 (0.3) -2.5 (0.3) sem=standard error of the mean *at baseline, a total nasal symptom score (sum of 4 individual symptoms) of at least 6 and a total non-nasal symptom score (sum of 4 individual symptoms) of at least 5 (each symptom scored 0 to 3 where 0=no symptom and 3=severe symptoms) was required for trial eligibility. tss ranges from 0=no symptoms to 24=maximal symptoms. **mean reduction in tss averaged over the 2-week treatment period. 14.2 perennial allergic rhinitis the clinical efficacy and safety of desloratadine 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 desloratadine 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 desloratadine tablets 5 mg once daily was shown to significantly reduce the total symptom score in patients with perennial allergic rhinitis (table 4). table 4 total symptom score (tss) changes in a 4-week clinical trial in patients with perennial allergic rhinitis treatment group (n) mean baseline* (sem) change from baseline ** (sem) placebo comparison (p-value) desloratadine 5 mg (337) 12.37 (0.18) -4.06 (0.21) p=0.01 placebo (337) 12.30 (0.18) -3.27 (0.21) sem=standard error of the mean * at baseline, average of total symptom score (sum of 5 individual nasal symptoms and 3 non-nasal symptoms, each symptom scored 0 to 3 where 0=no symptom and 3=severe symptoms) of atleast 10 was required for trial eligibility. tss ranges from 0=no symptoms to 24=maximal symptoms. **mean reduction in tss averaged over the 4-week treatment period.

ine orally disintegrating tablets? do not take desloratadine if you: are allergic to desloratadine or any of the ingredients in desloratadine orally disintegrating tablets. see the end of this leaflet for a complete list of ingredients. are allergic to loratadine (alavert, claritin). talk to your doctor before taking this medicine if you have any questions about whether or not to take this medicine. what should i tell my doctor before taking desloratadine orally disintegrating tablets? before you take desloratadine, tell your doctor if you: have liver or kidney problems. have any other medical conditions. are pregnant or plan to become pregnant. it is not known if desloratadine will harm your unborn baby. talk to your doctor if you are pregnant or plan to become pregnant. are breast-feeding or plan to breast-feed. desloratadine can pass into your breast milk . talk to your doctor about the best way to feed your baby if you take desloratadine. tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins and herbal supplements. desloratadine may affect the way other medicines work, and other medicines may affect how desloratadine works. especially tell your doctor if you take: ketoconazole (nizoral) erythromycin (ery-tab, eryc, pce) azithromycin (zithromax, zmax) antihistaminesfluoxetine (prozac) cimetidine (tagamet) know the medicines you take. keep a list of your medicines and show it to your doctor and pharmacist when you get a new medicine. how should i take desloratadine orally disintegrating tablets? take desloratadine exactly as your doctor tells you to take it. do not change your dose of desloratadine or take more often than prescribed. desloratadine can be taken with or without food. place desloratadine orally disintegrating tablets on your tongue and allow it to dissolve before swallowing. desloratadine orally disintegrating tablets can be taken with or without water. take your desloratadine orally disintegrating tablets right away after opening the blister. if you take too much desloratidine, call your doctor or get medical attention right away. what are the possible side effects of desloratadine orally disintegrating tablets? desloratadine may cause serious side effects, including: allergic reactions. stop taking desloratadine and call your doctor right away or get emergency help if you have any of these symptoms: rash itching hives swelling of your lips, tongue, face, and throat shortness of breath or trouble breathing the most common side effects of desloratadine in adults and children 12 years of age and older with allergic rhinitis include: sore throatd dry mouth muscle pain tiredness sleepiness menstrual pain increased sleepiness or tiredness can happen if you take more desloratadine than your doctor prescribed to you. tell your doctor if you have any side effect that bothers you or that does not go away. these are not all of the possible side effects of desloratadine. for more information, ask your doctor or pharmacist. call your doctor for medical advice about side effects. you may report side effects to fda at 1-800-fda-1088. how should i store desloratadine orally disintegrating tablets? store oraly disintegrating tablets at 20°-25°c (68°-77°f) excursions permitted to 15°-30°c (59°-86°f) [see usp controlled room temperature]. keep desloratadine orally disintegrating tablets, and all medicines out of the reach of children. general information about desloratadine medicines are sometimes prescribed for purposes other than those listed in a patient information leaflet. do not use desloratadine for a condition for which it was not prescribed. do not give desloratadine to other people, even if they have the same condition you have. it may harm them. this patient information leaflet summarizes the most important information about desloratadine. if you would like more information, talk with your doctor. you can ask your pharmacist or doctor for information about desloratadine that is written for health professionals. what are the ingredients in desloratadine orally disintegrating tablets? active ingredient: desloratadine patients with phenylketonuria: desloratadine orally disintegrating tablets 5 mg contain 10.10 mg phenylalanine, and desloratadine orally disintegrating tablets 2.5 mg contain 5 mg phenylalanine. inactive ingredients in desloratadine tablets: anhydrous citric acid, aspartame, colloidal silicon dioxide, crospovidone, ferric oxide, mannitol, lactose anhydrous, microcrystalline cellulose, polacrilex resin, sodium stearyl fumarate, talc, tutti frutti flavor. the trademarks depicted herein are owned by their respective companies. rx only manufactured by: dr. reddy's laboratories limited bachupally - 500 090 india revised: 0319 dispense with patient information sheet available at: www.drreddys.com/pi/desloratadineodtabs.pdf