ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS. The following adverse reactions are discussed in greater detail in other sections of the label:Hypersensitivity reactions. [See Warnings and Precautions (5.1).] Hypersensitivity reactions. [See Warnings and Precautions (5.1).] The most common adverse reactions (reported in >= 2% of adult and adolescent patients with allergic rhinitis and greater than placebo) were pharyngitis, dry mouth, myalgia, fatigue, somnolence, dysmenorrhea. (6.1)To report SUSPECTED ADVERSE REACTIONS, contact Sun Pharmaceutical Industries, Inc., at 1-866-923-4914 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.. The most common adverse reactions (reported in >= 2% of adult and adolescent patients with allergic rhinitis and greater than placebo) were pharyngitis, dry mouth, myalgia, fatigue, somnolence, dysmenorrhea. (6.1). 6.1 Clinical Trials Experience. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.Adults and AdolescentsAllergic Rhinitis: In multiple-dose placebo-controlled trials, 2,834 patients ages 12 years or older received desloratadine tablets at doses of 2.5 mg to 20 mg daily, of whom 1,655 patients received the recommended daily dose of mg. In patients receiving 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 TabletsAdverse EventDesloratadine Tablets5 mg (n 1,655)Placebo(n 1,652)Infections and InfestationsPharyngitis4.1%2%Nervous System DisordersSomnolence2.1%1.8%Gastrointestinal DisordersDry Mouth3%1.9%Musculoskeletal and Connective Tissue DisordersMyalgia2.1%1.8%Reproductive System and Breast DisordersDysmenorrhea2.1%1.6%General Disorders and Administration Site ConditionsFatigue2.1%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 subgroups of patients as defined by gender, age, or race.Chronic Idiopathic Urticaria: In multiple-dose, placebo-controlled trials of chronic idiopathic urticaria, 211 patients ages 12 years or older received desloratadine tablets and 205 received placebo. Adverse events that were reported by greater than or equal to 2% of patients who received desloratadine tablets and that were more common with desloratadine than placebo were (rates for desloratadine 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%). PediatricsTwo hundred and forty-six pediatric subjects months to 11 years of age received desloratadine oral solution for 15 days in three placebo-controlled clinical trials. Pediatric subjects aged to 11 years received 2.5 mg once day, subjects aged to years received 1.25 mg once day, and subjects to 11 months of age received 1.0 mg once day.In subjects to 11 years of age, no individual adverse event was reported by percent or more of the subjects.In subjects to years of age, adverse events reported for desloratadine and placebo in at least percent of subjects receiving desloratadine oral solution and at 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 percent of subjects receiving desloratadine oral solution and at 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 months to 11 months of age, adverse events reported for desloratadine and placebo in at least percent of subjects receiving desloratadine oral solution and at 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 oral solution in the clinical trials discontinued treatment because of an adverse event.. 6.2 Post-Marketing Experience. Because adverse events are reported voluntarily from population of uncertain size, it is not always possible to reliably estimate their frequency or establish causal relationship to drug exposure. The following spontaneous adverse events have been reported during the marketing of desloratadine:Cardiac disorders: tachycardia, palpitationsRespiratory, thoracic and mediastinal disorders: dyspneaSkin and subcutaneous tissue disorders: rash, pruritusNervous system disorders: psychomotor hyperactivity, movement disorders (including dystonia, tics, and extrapyramidal symptoms), seizures (reported in patients with and without known seizure disorder)Immune system disorders: hypersensitivity reactions (such as urticaria, edema and anaphylaxis)Investigations: elevated liver enzymes including bilirubinHepatobiliary disorders: hepatitisMetabolism and nutrition disorders: increased appetite.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. Carcinogenicity StudiesThe carcinogenic potential of desloratadine was assessed using loratadine study in rats and desloratadine study in mice. In 2-year study in rats, loratadine was administered in the diet at doses up to 25 mg/kg/day (estimated desloratadine and desloratadine metabolite exposures were approximately 30 times the AUC in humans at the recommended daily oral dose). significantly higher incidence of hepatocellular tumors (combined adenomas and carcinomas) was observed in males given 10 mg/kg/day of loratadine and in males and females given 25 mg/kg/day of loratadine. The estimated desloratadine and desloratadine metabolite exposures in rats given 10 mg/kg of loratadine were approximately 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 2-year dietary study in mice, males and females given up to 16 mg/kg/day and 32 mg/kg/day desloratadine, respectively, did not show significant increases in the incidence of any tumors. The estimated desloratadine and desloratadine metabolite exposures in mice at these doses were 12 and 27 times, respectively, the AUC in humans at the recommended daily oral dose.Genotoxicity StudiesIn genotoxicity studies with desloratadine, there was no evidence of genotoxic potential in reverse mutation assay (Salmonella/E. coli mammalian microsome bacterial mutagenicity assay) or in assays for chromosomal aberrations (human peripheral blood lymphocyte clastogenicity assay and mouse bone marrow micronucleus assay).Impairment of FertilityThere 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 and desloratadine metabolite 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 mg/kg/day (estimated desloratadine and desloratadine metabolite exposures were approximately times the AUC in humans at the recommended daily oral dose).

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY. 12.1 Mechanism of Action. Desloratadine is long-acting tricyclic histamine antagonist with selective H1-receptor histamine antagonist activity. Receptor binding data indicates that at 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 radiolabeled tissue distribution study in rats and radioligand H1- receptor binding study in guinea pigs showed that desloratadine did not readily cross the blood brain barrier. The clinical significance of this finding is unknown. 12.2 Pharmacodynamics. Wheal and Flare: Human histamine skin wheal studies following single and repeated 5-mg doses of desloratadine have shown that the drug exhibits an antihistaminic effect by 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. Effects on QTc: 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 blinded fashion by 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 (QTc) by both the Bazett and Fridericia methods. Using the QTc (Bazett) there was mean increase of 8.1 msec in desloratadine-treated subjects relative to placebo. Using QTc (Fridericia) there was mean increase of 0.4 msec in desloratadine-treated subjects relative to placebo. No clinically relevant adverse events were reported. 12.3 Pharmacokinetics. Absorption: Following oral administration of desloratadine mg tablet once daily for 10 days to normal healthy volunteers, the mean time to maximum plasma concentrations (Tmax) occurred at approximately hours post dose and mean steady state peak plasma concentrations (Cmax) and AUC of ng/mL and 56.9 nghr/mL were observed, respectively. Neither food nor grapefruit juice had an effect on the bioavailability (Cmax and AUC) of desloratadine. The pharmacokinetic profile of desloratadine oral solution was evaluated in three-way crossover study in 30 adult volunteers. single dose of 10 mL of desloratadine oral solution containing mg of desloratadine was bioequivalent to single dose of mg desloratadine tablet. Food had no effect on the bioavailability (AUC and Cmax) of desloratadine oral solution. 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 subset of the general population has decreased ability to form 3-hydroxydesloratadine, and are poor metabolizers of desloratadine. In pharmacokinetic studies (n=3,748), approximately 6% of subjects were poor metabolizers of desloratadine (defined as subject with an AUC ratio of 3-hydroxydesloratadine to desloratadine less than 0.1, or subject with desloratadine half-life exceeding 50 hours). These pharmacokinetic studies included subjects between the ages of and 70 years, including 977 subjects aged to years, 1,575 subjects aged to 11 years, and 1196 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, 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. Cmax and AUC values increased in dose proportional manner following single oral doses between and 20 mg. The degree of accumulation after 14 days of dosing was consistent with the half-life and dosing frequency. human mass balance study documented 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 Tmax and half-life values compared to desloratadine. Special Populations Geriatric Subjects: In older subjects (>=65 years old; n=17) following multiple-dose administration of desloratadine tablets, the mean Cmax 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 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 to 11 years old, single dose of mL of desloratadine oral solution containing 2.5 mg of desloratadine, resulted in desloratadine plasma concentrations similar to those achieved in adults administered single mg desloratadine tablet. In subjects to years old, 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 single 5-mg desloratadine tablet. However, the Cmax and AUC of the metabolite (3-hydroxydesloratadine) were 1.27 and 1.61 times higher for the mg dose of oral solution administered in adults compared to the Cmax and AUC obtained in children to 11 years of age receiving 1.25 to 2.5 mg of desloratadine oral solution. 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 to 11 months of age and 12 to 23 months of age. The results of population pharmacokinetic analysis indicated that dose of mg for subjects aged 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 single 5-mg dose of desloratadine oral solution. Renally Impaired: Desloratadine pharmacokinetics following single dose of 7.5 mg were characterized in patients with mild (n=7; creatinine clearance 51 to 69 mL/min/1.73 m2), moderate (n=6; creatinine clearance 34 to 43 mL/min/1.73 m2), and severe (n=6; creatinine clearance to 29 mL/min/1.73 m2) renal impairment or hemodialysis dependent (n=6) patients. In patients with mild and moderate renal impairment, median Cmax 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, Cmax 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 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 subjects with normal hepatic function. Patients with hepatic impairment, regardless of severity, had approximately 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 Cmax 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 Cmax and AUC values, respectively, compared with male subjects. The 3-hydroxydesloratadine Cmax 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 Cmax and AUC values for desloratadine were 18% and 32% higher, respectively, in Blacks compared with Caucasians. For 3-hydroxydesloratadine there was corresponding 10% reduction in Cmax 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 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 mg has been coadministered with azithromycin 500 mg followed by 250 mg once daily for days (n=18) or with fluoxetine 20 mg once daily for days after 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 (Cmax 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 VolunteersDesloratadine3- HydroxydesloratadineCmaxAUC0-24 hrsCmaxAUC0-24 hrsErythromycin(500 mg Q8h)+ 24%+ 14%+ 43%+ 40%Ketoconazole(200 mg Q12h)+ 45%+ 39%+ 43%+ 72%Azithromycin(500 mg day 1, 250 mg QD 4 days)+ 15%+ 5%+ 15%+ 4%Fluoxetine(20 mg QD)+ 15%+ 0%+ 17%+ 13%Cimetidine(600 mg Q12h)+ 12%+ 19%- 11%- 3%.

CLINICAL STUDIES SECTION.

14 CLINICAL STUDIES. 14.1 Seasonal Allergic Rhinitis. The clinical efficacy and safety of desloratadine 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 to 20 mg/day of desloratadine in doubleblind, randomized, placebo-controlled clinical trials of to weeks duration conducted in the United States. The results of these studies demonstrated the efficacy and safety of desloratadine mg in the treatment of adult and adolescent patients with seasonal allergic rhinitis. In dose-ranging trial, desloratadine 2.5 to 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 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 allergicrhinitis and concomitant asthma, desloratadine tablets 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 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 2-Week Clinical Trial in Patients with Seasonal Allergic RhinitisTreatment Group (n)Mean Baseline (SEM)Change from Baseline (SEM)Placebo Comparison P-value) Desloratadine5 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, total nasal symptom score (sum of individual symptoms) of at least and total non-nasal symptom score (sum of individual symptoms) of at least (each symptom scored to 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. There were no significant differences in the effectiveness of desloratadine tablets mg across subgroups of patients defined by gender, age, or race. 14.2 Perennial Allergic Rhinitis. The clinical efficacy and safety of desloratadine tablets mg were evaluated in over 1,300 patients 12 to 80 years of age with perennial allergic rhinitis. total of 685 patients received mg/day of desloratadine in two double-blind, randomized,placebo-controlled clinical trials of weeks duration conducted in the United States and internationally. In one of these studies desloratadine tablets mg once daily was shown to significantly reduce the Total Symptom Score in patients withperennial allergic rhinitis (Table 4).Table 4: TOTAL SYMPTOM SCORE (TSS) Changes in 4 Week Clinical Trial in Patients with Perennial Allergic RhinitisTreatment Group (n)Mean Baseline (SEM)Change from Baseline (SEM)Placebo Comparison P-value) Desloratadine5 mg (337)12.37 (0.18)-4.06 (0.21)P=0.01 Placebo (337) 12.30 (0.18)-3.27 (0.21) At baseline, average of total symptom score (sum of individual nasal symptoms and non-nasal symptoms, each symptom scored to where 0=no symptom and 3=severe symptoms) of at least 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.SEM=Standard Error of the Mean. 14.3 Chronic Idiopathic Urticaria. The efficacy and safety of desloratadine tablets mg once daily was studied in 416 chronic idiopathic urticaria patients 12 to 84 years of age, of whom 211 received desloratadine. In two double-blind, placebo-controlled, randomized clinical trials of six weeks duration, at the pre-specified one-week primary time point evaluation, desloratadine tablets significantly reduced the severity of pruritus when compared to placebo (Table 5). Secondary endpoints were also evaluated, and during the first week of therapy desloratadine tablets mg reduced the secondary endpoints, Number of Hives and the Size of the Largest Hive, when compared to placebo.Table 5: PRURITUS SYMPTOM SCORE Changes in the First Week of Clinical Trial in Patients with Chronic Idiopathic UrticariaTreatment Group (n)Mean Baseline (SEM)Change from Baseline (SEM)Placebo Comparison P-value) Desloratadine5 mg (115)2.19 (0.04)-1.05 (0.07)P<0.01 Placebo (110) 2.21 (0.04)-0.52 (0.07)Pruritus scored to where 0=no symptom to 3=maximal symptom Mean reduction in pruritus averaged over the first week of treatment.SEM=Standard Error of the MeanThe clinical safety of desloratadine oral solution was documented in three, 15-day, double-blind, placebo-controlled safety studies in pediatric subjects with documented history of allergic rhinitis, chronic idiopathic urticaria, or subjects who were candidates for antihistamine therapy. In the first study, 2.5 mg of desloratadine oral solution was administered to 60 pediatric subjects to 11years of age. The second study evaluated 1.25 mg of desloratadine oral solution administered to 55 pediatric subjects to years of age. In the third study, 1.25 mg of desloratadine oral solution was administered to 65 pediatric subjects 12 to 23 months of age and 1.0 mg of desloratadine oral solution was administered to 66 pediatric subjects to 11 months of age. The results of these studies demonstrated the safety of desloratadine oral solution in pediatric subjects months to 11 years of age.

CLINICAL TRIALS EXPERIENCE SECTION.

6.1 Clinical Trials Experience. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.Adults and AdolescentsAllergic Rhinitis: In multiple-dose placebo-controlled trials, 2,834 patients ages 12 years or older received desloratadine tablets at doses of 2.5 mg to 20 mg daily, of whom 1,655 patients received the recommended daily dose of mg. In patients receiving 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 TabletsAdverse EventDesloratadine Tablets5 mg (n 1,655)Placebo(n 1,652)Infections and InfestationsPharyngitis4.1%2%Nervous System DisordersSomnolence2.1%1.8%Gastrointestinal DisordersDry Mouth3%1.9%Musculoskeletal and Connective Tissue DisordersMyalgia2.1%1.8%Reproductive System and Breast DisordersDysmenorrhea2.1%1.6%General Disorders and Administration Site ConditionsFatigue2.1%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 subgroups of patients as defined by gender, age, or race.Chronic Idiopathic Urticaria: In multiple-dose, placebo-controlled trials of chronic idiopathic urticaria, 211 patients ages 12 years or older received desloratadine tablets and 205 received placebo. Adverse events that were reported by greater than or equal to 2% of patients who received desloratadine tablets and that were more common with desloratadine than placebo were (rates for desloratadine 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%). PediatricsTwo hundred and forty-six pediatric subjects months to 11 years of age received desloratadine oral solution for 15 days in three placebo-controlled clinical trials. Pediatric subjects aged to 11 years received 2.5 mg once day, subjects aged to years received 1.25 mg once day, and subjects to 11 months of age received 1.0 mg once day.In subjects to 11 years of age, no individual adverse event was reported by percent or more of the subjects.In subjects to years of age, adverse events reported for desloratadine and placebo in at least percent of subjects receiving desloratadine oral solution and at 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 percent of subjects receiving desloratadine oral solution and at 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 months to 11 months of age, adverse events reported for desloratadine and placebo in at least percent of subjects receiving desloratadine oral solution and at 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 oral solution in the clinical trials discontinued treatment because of an adverse event.

CONTRAINDICATIONS SECTION.

4 CONTRAINDICATIONS. Desloratadine oral solution is contraindicated in patients who are hypersensitive to this medication or to any of its ingredients or to loratadine [see Warnings and Precautions (5.1) and Adverse Reactions (6.2)]. o Hypersensitivity (4, 6.2).

DESCRIPTION SECTION.

11 DESCRIPTION. Desloratadine oral solution is clear, colorless to slightly yellow solution containing 0.5 mg/mL desloratadine. It contains the following inactive ingredients: bubble gum flavor, butylated hydroxyanisole, citric acid anhydrous, glycerin, maltitol solution, polyethylene glycol 400, propylene glycol, purified water, sodium benzoate, sodium citrate dihydrate, sorbitol solution and sucralose powder.Desloratadine, USP is white to beige powder that is slightly soluble in water, but very soluble in ethanol and propylene glycol. It has an empirical formula: C19H19ClN2 and 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:. structure.

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION. Desloratadine oral solution may be taken without regard to meals.The age-appropriate dose of desloratadine oral solution should be administered with commercially available measuring dropper or syringe that is calibrated to deliver mL and 2.5 mL 1/2 teaspoon).. Dosage (by age):Adults and Adolescents 12 Years of Age and Over:2 teaspoonfuls (5 mg in 10 mL) once daily (2)Children to 11 Years of Age:1 teaspoonful (2.5 mg in mL) once dailyChildren 12 Months to Years of Age: 1/2 teaspoonful (1.25 mg in 2.5 mL) once daily (2). teaspoonfuls (5 mg in 10 mL) once daily (2). teaspoonful (2.5 mg in mL) once daily. 1/2 teaspoonful (1.25 mg in 2.5 mL) once daily (2). 2.1 Adults and Adolescents 12 Years of Age and Over. The recommended dose of desloratadine oral solution is teaspoonfuls (5 mg in 10 mL) once daily.. 2.2 Children to 11 Years of Age. The recommended dose of desloratadine oral solution is teaspoonful (2.5 mg in mL) once daily.. 2.3 Children 12 Months to Years of Age. The recommended dose of desloratadine oral solution is 1/2 teaspoonful (1.25 mg in 2.5 mL) once daily.. 2.4 Children to 11 Months of Age. The recommended dose of desloratadine oral solution is mL (1 mg) once daily.. 2.5 Adults with Hepatic or Renal Impairment. Dosing recommendation for children with liver or renal impairment cannot be made due to lack of data [see Clinical Pharmacology (12.3)].

DOSAGE FORMS & STRENGTHS SECTION.

3 DOSAGE FORMS AND STRENGTHS. Desloratadine oral solution is clear, colorless to slightly yellow solution containing 0.5 mg desloratadine/1 mL.. Desloratadine Oral Solution 0.5 mg/1 mL (3).

DRUG INTERACTIONS SECTION.

7 DRUG INTERACTIONS. 7.1 Inhibitors of Cytochrome P450 3A4. In controlled clinical studies co-administration of desloratadine with ketoconazole, erythromycin, or azithromycin resulted in increased plasma concentrations of desloratadine and hydroxydesloratadine, but there were no clinically relevant changes in the safety profile of desloratadine. [See Clinical Pharmacology (12.3).] 7.2 Fluoxetine. In controlled clinical studies co-administration of desloratadine with fluoxetine, selective serotonin reuptake inhibitor (SSRI), resulted in increased plasma concentrations of desloratadine and hydroxydesloratadine, but there were no clinically relevant changes in the safety profile of desloratadine. [See Clinical Pharmacology (12.3).] 7.3 Cimetidine. In controlled clinical studies co-administration of desloratadine with cimetidine, histamine H2-receptor antagonist, resulted in increased plasma concentrations of desloratadine and hydroxydesloratadine, but there were no clinically relevant changes in the safety profile of desloratadine. [See Clinical Pharmacology (12.3).].

GERIATRIC USE SECTION.

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 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 (12.3).].

HEPATIC IMPAIRMENT SUBSECTION.

8.7 Hepatic Impairment. Dosage adjustment for patients with hepatic impairment is recommended [see Dosage and Administration (2.5) and Clinical Pharmacology (12.3)].

HOW SUPPLIED SECTION.

16 HOW SUPPLIED/STORAGE AND HANDLING. Desloratadine oral solution is clear, colorless to slightly yellow solution with characteristic bubble gum odor containing 0.5 mg/mL desloratadine and is available in the following size:4 fl oz (118 mL) NDC 74157-011-01.Store at 20 to 25 (68 to 77 F) [see USP Controlled Room Temperature]. Protect from light.

INDICATIONS & USAGE SECTION.

1 INDICATIONS AND USAGE. Desloratadine Oral Solution is histamine-1 (H1) receptor antagonist indicated for:Seasonal Allergic Rhinitis: relief of nasal and non-nasal symptoms in patients years of age and older. (1.1) Perennial Allergic Rhinitis: relief of nasal and non-nasal symptoms in patients months of age and older. (1.2) Chronic Idiopathic Urticaria: symptomatic relief of pruritus, reduction in the number of hives, and size of hives in patients months of age and older. (1.3) Seasonal Allergic Rhinitis: relief of nasal and non-nasal symptoms in patients years of age and older. (1.1) Perennial Allergic Rhinitis: relief of nasal and non-nasal symptoms in patients months of age and older. (1.2) Chronic Idiopathic Urticaria: symptomatic relief of pruritus, reduction in the number of hives, and size of hives in patients months of age and older. (1.3) 1.1 Seasonal Allergic Rhinitis Desloratadine oral solution is indicated for the relief of the nasal and non-nasal symptoms of seasonal allergic rhinitis in patients years of age and older.. 1.2 Perennial Allergic Rhinitis. Desloratadine oral solution is indicated for the relief of the nasal and non-nasal symptoms of perennial allergic rhinitis in patients months of age and older.. 1.3 Chronic Idiopathic Urticaria. Desloratadine oral solution is indicated for the symptomatic relief of pruritus, reduction in the number of hives, and size of hives, in patients with chronic idiopathic urticaria months of age and older.

INFORMATION FOR PATIENTS SECTION.

17.1 Information for Patients. Patients should be instructed to use desloratadine as directed.As there are no food effects on bioavailability, patients can be instructed that desloratadine oral solution 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. Patients should be instructed to use desloratadine as directed.. As there are no food effects on bioavailability, patients can be instructed that desloratadine oral solution 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.

LACTATION SECTION.

8.2 Lactation. Risk SummaryDesloratadine 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 mothers clinical need, and any potential adverse effects on the breastfed infant from desloratadine or from the underlying maternal condition.

MECHANISM OF ACTION SECTION.

12.1 Mechanism of Action. Desloratadine is long-acting tricyclic histamine antagonist with selective H1-receptor histamine antagonist activity. Receptor binding data indicates that at 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 radiolabeled tissue distribution study in rats and radioligand H1- receptor binding study in guinea pigs showed that desloratadine did not readily cross the blood brain barrier. The clinical significance of this finding is unknown.

NONCLINICAL TOXICOLOGY SECTION.

13 NONCLINICAL TOXICOLOGY. 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. Carcinogenicity StudiesThe carcinogenic potential of desloratadine was assessed using loratadine study in rats and desloratadine study in mice. In 2-year study in rats, loratadine was administered in the diet at doses up to 25 mg/kg/day (estimated desloratadine and desloratadine metabolite exposures were approximately 30 times the AUC in humans at the recommended daily oral dose). significantly higher incidence of hepatocellular tumors (combined adenomas and carcinomas) was observed in males given 10 mg/kg/day of loratadine and in males and females given 25 mg/kg/day of loratadine. The estimated desloratadine and desloratadine metabolite exposures in rats given 10 mg/kg of loratadine were approximately 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 2-year dietary study in mice, males and females given up to 16 mg/kg/day and 32 mg/kg/day desloratadine, respectively, did not show significant increases in the incidence of any tumors. The estimated desloratadine and desloratadine metabolite exposures in mice at these doses were 12 and 27 times, respectively, the AUC in humans at the recommended daily oral dose.Genotoxicity StudiesIn genotoxicity studies with desloratadine, there was no evidence of genotoxic potential in reverse mutation assay (Salmonella/E. coli mammalian microsome bacterial mutagenicity assay) or in assays for chromosomal aberrations (human peripheral blood lymphocyte clastogenicity assay and mouse bone marrow micronucleus assay).Impairment of FertilityThere 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 and desloratadine metabolite 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 mg/kg/day (estimated desloratadine and desloratadine metabolite exposures were approximately times the AUC in humans at the recommended daily oral dose).

OVERDOSAGE SECTION.

10 OVERDOSAGE. 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.Information regarding acute overdosage is limited to experience from post-marketing adverse event reports and from clinical trials conducted during the development of the desloratadine product. In dose-ranging trial, at doses of 10 mg and 20 mg/day somnolence was reported.In another study, no clinically relevant adverse events were reported in normal male and female volunteers who were given single daily doses of desloratadine 45 mg for 10 days [see Clinical Pharmacology (12.2)].

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

Desloratadine Oral Solution 0.5 mg/mL NDC 74157-011-01 bottle. carton.

PATIENT COUNSELING INFORMATION.

17 PATIENT COUNSELING INFORMATION. See FDA-Approved Patient Labeling (Patient Information).. 17.1 Information for Patients. Patients should be instructed to use desloratadine as directed.As there are no food effects on bioavailability, patients can be instructed that desloratadine oral solution 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. Patients should be instructed to use desloratadine as directed.. As there are no food effects on bioavailability, patients can be instructed that desloratadine oral solution 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.

PATIENT MEDICATION INFORMATION SECTION.

PATIENT INFORMATION Desloratadine Oral Solution. Read the Patient Information that comes with desloratadine before you start taking it and each time you get refill. There may be new information.This leaflet is summary of the information for patients. Your doctor or pharmacist can give youadditional information. This leaflet does not take the place of talking to your doctor about your medical condition or treatment.What is desloratadine oral solutionDesloratadine oral solution is prescriptionmedicine that contains the medicine desloratadine (an antihistamine).Desloratadine oral solution is used to help control the symptoms of:o seasonal allergic rhinitis (sneezing, stuffy nose, runny nose and itching of the nose) in people years of age and older.o perennial allergic rhinitis (sneezing, stuffy nose, runny nose and itching of the nose) in people months of age and older.o chronic idiopathic urticaria (long-term itching) and to reduce the number and size of hives in people months of age and older.Desloratadine oral solution is not for children younger than months of age.Who should not take desloratadine oral solutionDo not take desloratadine oral solution if you:o are allergic to desloratadine oral solution or any of the ingredients in desloratadine oral solution.See the end of this leaflet for complete list of ingredients.o 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 tell my doctor before taking desloratadine oral solutionBefore you take desloratadine oral solution, tell your doctor if you:o have liver or kidney problems.o have any other medical conditions.o are pregnant or plan to become pregnant. It is not known if desloratadine oral solution will harm your unborn baby. Talk to your doctor if you are pregnant or plan to become pregnant.o 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 oral solution.Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins and herbal supplements. Desloratadine oral solution may affect the way other medicines work, and other medicines may affect how desloratadine oral solution works. Especially tell your doctor if you take:o ketoconazole (Nizoral)o erythromycin (Ery-tab, Eryc, PCE)o azithromycin (Zithromax, Zmax)o antihistamineso fluoxetine (Prozac)o cimetidine (Tagamet)Know the medicines you take. Keep list of your medicines and show it to your doctor and pharmacist when you get new medicine.How should take desloratadine oral solutiono Take desloratadine oral solution exactly as your doctor tells you to take it.o Do not change your dose of desloratadine oral solution or take more often than prescribed.o Desloratadine oral solution can be taken with or without food.o Take desloratadine oral solution with measuring dropper or oral syringe that can measure mL or 2.5 mL. Ask your pharmacistfor dropper or syringe if you do not have one.o If you take too much desloratadine oral solution, call your doctor or get medical attention right away.What are the possible side effects of desloratadine oral solutionDesloratadine may cause serious side effects, including:o Allergic reactions. Stop taking desloratadine oral solution and call your doctor right away or get emergency help if you have any of these symptoms:o rasho itchingo hiveso swelling of your lips, tongue, face, and throato shortness of breath or trouble breathingThe most common side effects of desloratadine oral solution in adults and children 12 years of age and older with allergic rhinitis include:o sore throato dry moutho muscle paino tirednesso sleepinesso menstrual painIncreased sleepiness or tiredness can happen if you take more desloratadine oral solution 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 oral solution. 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 store desloratadine oral solutiono Store desloratadine oral solution between 68F to 77F (20C to 25C). Protect desloratadine oral solution from light.o Keep desloratadine oral solution and all medicines out of the reach of children.General information about desloratadine oral solutionMedicines are sometimes prescribed for purposes other than those listed in patient information leaflet. Do not use desloratadineoral solution for condition for which it was not prescribed. Do not give desloratadine oral solution 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 oral solution. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about desloratadine oral solution that is written for health professionals.What are the ingredients in desloratadine oral solutionActive ingredient: desloratadine Inactive ingredients: bubble gum flavor, butylated hydroxyanisole, citric acid anhydrous, glycerin, maltitol solution, polyethylene glycol 400, propylene glycol, purified water, sodium benzoate, sodium citrate dihydrate, sorbitol solution and sucralose powder. All trademarks are the property of their respective owners.Mfd. for:INA Pharmaceutics Inc.,Fairmont, WV 26554Revised: July 20255258608-0725-00 764.

PEDIATRIC USE SECTION.

8.4 Pediatric Use. The recommended dose of desloratadine oral solution in the pediatric population is based on cross-study comparison of the plasma concentration of desloratadine in adults and pediatric subjects. The safety of desloratadine oral solution has been established in 246 pediatric subjects aged 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 desloratadine are sufficiently similar in the pediatric and adult populations, it allows extrapolation from the adult efficacy data to pediatric patients. The effectiveness of desloratadine oral solution in these age groups is supported by evidence from adequate and well-controlled studies of desloratadine tablets in adults. The safety and effectiveness of desloratadine oral solution has not been demonstrated in pediatric patients less than months of age. [See Clinical Pharmacology (12.3).].

PHARMACODYNAMICS SECTION.

12.2 Pharmacodynamics. Wheal and Flare: Human histamine skin wheal studies following single and repeated 5-mg doses of desloratadine have shown that the drug exhibits an antihistaminic effect by 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. Effects on QTc: 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 blinded fashion by 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 (QTc) by both the Bazett and Fridericia methods. Using the QTc (Bazett) there was mean increase of 8.1 msec in desloratadine-treated subjects relative to placebo. Using QTc (Fridericia) there was mean increase of 0.4 msec in desloratadine-treated subjects relative to placebo. No clinically relevant adverse events were reported.

POSTMARKETING EXPERIENCE SECTION.

6.2 Post-Marketing Experience. Because adverse events are reported voluntarily from population of uncertain size, it is not always possible to reliably estimate their frequency or establish causal relationship to drug exposure. The following spontaneous adverse events have been reported during the marketing of desloratadine:Cardiac disorders: tachycardia, palpitationsRespiratory, thoracic and mediastinal disorders: dyspneaSkin and subcutaneous tissue disorders: rash, pruritusNervous system disorders: psychomotor hyperactivity, movement disorders (including dystonia, tics, and extrapyramidal symptoms), seizures (reported in patients with and without known seizure disorder)Immune system disorders: hypersensitivity reactions (such as urticaria, edema and anaphylaxis)Investigations: elevated liver enzymes including bilirubinHepatobiliary disorders: hepatitisMetabolism and nutrition disorders: increased appetite.

PREGNANCY SECTION.

8.1 Pregnancy. Risk SummaryThe limited available data with desloratadine in pregnant women are not sufficient to inform drug-associated risk for major birth defects and miscarriage. There are no adequate and well-controlled studies in pregnant women. Desloratadine given during organogenesis to pregnant rats was not teratogenic at the summed area under the concentration-time curve (AUC)-based exposures of desloratadine and its metabolite approximately 320 times that at the recommended human daily oral dose (RHD) of mg/day. Desloratadine given during organogenesis to pregnant rabbits was not teratogenic at the AUC-based exposures of desloratadine approximately 230 times that at the RHD. Desloratadine given to pregnant rats during organogenesis through lactation resulted in reduced body weight and slow righting reflex of F1 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 to 4% and 15 to 20%, respectively.DataAnimal DataDesloratadine 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 peri-and post-natal development study, desloratadine was given to rats orally during the perinatal (Gestation Day 6) through lactation periods (Postpartum Day 21) at doses of 3, and 18 mg/kg/day. Reduced body weight and slow righting reflex were reported in F1 pups at doses of 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 F1 pup development at 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 F0 dams. F1 offspring were subsequently mated and there was no developmental toxicity for F2 pups observed.

RENAL IMPAIRMENT SUBSECTION.

8.6 Renal Impairment. Dosage adjustment for patients with renal impairment is recommended [see Dosage and Administration (2.5) and Clinical Pharmacology (12.3)].

SPL UNCLASSIFIED SECTION.

Mfd. for: INA Pharmaceutics Inc., Fairmont, WV 26554 Revised: July 2025 5258608-0725-00 764.

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATATIONS. Renal impairment: dosage adjustment is recommended (2.5, 8.6, 12.3)Hepatic impairment: dosage adjustment is recommended (2.5, 8.7, 12.3)See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.. Renal impairment: dosage adjustment is recommended (2.5, 8.6, 12.3). Hepatic impairment: dosage adjustment is recommended (2.5, 8.7, 12.3). 8.1 Pregnancy. Risk SummaryThe limited available data with desloratadine in pregnant women are not sufficient to inform drug-associated risk for major birth defects and miscarriage. There are no adequate and well-controlled studies in pregnant women. Desloratadine given during organogenesis to pregnant rats was not teratogenic at the summed area under the concentration-time curve (AUC)-based exposures of desloratadine and its metabolite approximately 320 times that at the recommended human daily oral dose (RHD) of mg/day. Desloratadine given during organogenesis to pregnant rabbits was not teratogenic at the AUC-based exposures of desloratadine approximately 230 times that at the RHD. Desloratadine given to pregnant rats during organogenesis through lactation resulted in reduced body weight and slow righting reflex of F1 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 to 4% and 15 to 20%, respectively.DataAnimal DataDesloratadine 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 peri-and post-natal development study, desloratadine was given to rats orally during the perinatal (Gestation Day 6) through lactation periods (Postpartum Day 21) at doses of 3, and 18 mg/kg/day. Reduced body weight and slow righting reflex were reported in F1 pups at doses of 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 F1 pup development at 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 F0 dams. F1 offspring were subsequently mated and there was no developmental toxicity for F2 pups observed.. 8.2 Lactation. Risk SummaryDesloratadine 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 mothers 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. 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 desloratadine dose of 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 recommended dose of desloratadine oral solution in the pediatric population is based on cross-study comparison of the plasma concentration of desloratadine in adults and pediatric subjects. The safety of desloratadine oral solution has been established in 246 pediatric subjects aged 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 desloratadine are sufficiently similar in the pediatric and adult populations, it allows extrapolation from the adult efficacy data to pediatric patients. The effectiveness of desloratadine oral solution in these age groups is supported by evidence from adequate and well-controlled studies of desloratadine tablets in adults. The safety and effectiveness of desloratadine oral solution has not been demonstrated in pediatric patients less than months of age. [See Clinical Pharmacology (12.3).] 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 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 (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)].

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS. Hypersensitivity reactions including rash, pruritus, urticaria, edema, dyspnea, and anaphylaxis have been reported. In such cases, stop desloratadine at once and consider alternative treatments. (5.1). Hypersensitivity reactions including rash, pruritus, urticaria, edema, dyspnea, and anaphylaxis have been reported. In such cases, stop desloratadine at once and consider alternative treatments. (5.1). 5.1 Hypersensitivity Reactions. Hypersensitivity reactions including rash, pruritus, urticaria, edema, dyspnea, and anaphylaxis have been reported after administration of desloratadine. If such reaction occurs, therapy with desloratadine should be stopped and alternative treatment should be considered. [See Adverse Reactions (6.2).].