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).] The following adverse reactions are discussed in greater detail in other sections of the label:. 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 Belcher Pharmaceuticals LLC at 1-727-471-0850 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 1Incidence of Adverse Events Reported by >=2% of Adult and Adolescent AllergicRhinitis Patients Receiving Desloratadine Tablets Adverse Event Desloratadine Tablets mg (n=1,655) Placebo (n=1,652) 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 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 (3.0%, 1.6%), and nausea (3.0%, 0%).There were no clinically meaningful changes in any electrocardiographic parameter, including the QTc interval. Only one of the 246 pediatric subjects receiving 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: tachycardia, palpitations, rare cases of hypersensitivity reactions (such as rash, pruritus, urticaria, edema, dyspnea, and anaphylaxis), psychomotor hyperactivity, seizures, and elevated liver enzymes including bilirubin, and very rarely, hepatitis.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity Studies:The 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 Studies:In 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 Fertility:There was no effect on female fertility in rats at desloratadine doses up to 24 mg/kg/day (estimated desloratadine and desloratadine metabolite exposures were approximately 130 times the AUC in humans at the recommended daily oral dose). 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 AbsorptionFollowing oral administration of desloratadine mg tablet once daily for 10 days to normal healthy volunteers, the mean time to maximum plasma concentrations (T max) occurred at approximately hours post dose and mean steady state peak plasma concentrations (C max) and AUC of ng/mL and 56.9 nghr/mL were observed, respectively. Neither food nor grapefruit juice had an effect on the bioavailability (C max and AUC) of desloratadine. The pharmacokinetic profile of 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 max) of Desloratadine Oral Solution. DistributionDesloratadine 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.MetabolismDesloratadine (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 15-35 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.EliminationThe mean plasma elimination half-life of desloratadine was approximately 27 hours. max 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 max and half-life values compared to desloratadine. Special PopulationsGeriatric Subjects: In older subjects (>=65 years old; n=17) following multiple-dose administration of Desloratadine Tablets, the mean max and AUC values for desloratadine were 20% greater than in younger subjects (<65 years old). The oral total body clearance (CL/F) when normalized for body weight was similar between the two age groups. The mean plasma elimination half-life of desloratadine was 33.7 hr in subjects >=65 years old. The 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 max 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 max and AUC obtained in children to 11 years of age receiving 1.25-2.5 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 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 51-69 mL/min/1.73 2), moderate (n=6; creatinine clearance 34-43 mL/min/1.73 2), and severe (n=6; creatinine clearance 5-29 mL/min/1.73 2) renal impairment or hemodialysis dependent (n=6) patients. In patients with mild and moderate renal impairment, median 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, 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 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 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 max and AUC values, respectively, compared with male subjects. The 3-hydroxydesloratadine 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 max 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 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 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 (C max and AUC 0-24 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 2Changes in Desloratadine and 3-HydroxydesloratadinePharmacokinetics in Healthy Male and Female VolunteersDesloratadine3-HydroxydesloratadineC max AUC 0-24hrs 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 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. total of 1,838 patients received 2.5 to 20 mg/day of Desloratadine in double-blind, 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 5.0 mg. In the same study, an increase in the incidence of somnolence was observed at doses of 10 mg/day and 20 mg/day (5.2% and 7.6%, respectively), compared to placebo (2.3%).In two 4-week studies of 924 patients (aged 15 to 75 years) with seasonal allergic rhinitis and concomitant asthma, 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 3TOTAL SYMPTOM SCORE (TSS)Changes in 2 Week Clinical Trial in Patients with Seasonal Allergic Rhinitis Treatment Group (n) Mean Baseline (SEM) Change from Baseline (SEM) Placebo Comparison (P-value) 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 - week treatment period. SEM Standard Error of the Mean Desloratadine mg (171) 14.2 (0.3)-4.3 (0.3)P<0.01Placebo (173)13.7 (0.3)-2.5 (0.3)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 with perennial allergic rhinitis Table 4). Table 4TOTAL SYMPTOM SCORE (TSS)Changes in 4 Week Clinical Trial in Patients with Perennial Allergic Rhinitis Treatment Group (n) Mean Baseline (SEM) Change from Baseline (SEM) Placebo Comparison (P-value) 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 week treatment period. SEM Standard Error of the Mean Desloratadine5 mg (337)12.37 (0.18)-4.06 (0.21)P=0.01Placebo (337)12.30 (0.18)-3.27 (0.21). 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 5PRURITUS SYMPTOM SCOREChanges in the First Week of Clinical Trial in Patients with Chronic Idiopathic Urticaria Treatment Group (n) Mean Baselinex (SEM) Change from Baseline (SEM) Placebo Comparison (P-value) Pruritus scored to where 0=no symptom to 3=maximum symptom Mean reduction in Pruritus averaged over the first week of treatment. SEM Standard Error of the Mean Desloratadine mg (115) 2.19 (0.04)-1.05 (0.07)P=0.01Placebo (110)2.21 (0.04)-0.52 (0.07).

INFORMATION FOR PATIENTS SECTION.

17 PATIENT COUNSELING INFORMATION [See FDA-Approved Patient Labeling].. 17.1 Information for Patients. Patients should be instructed to use Desloratadine Tablets as directed.As there are no food effects on bioavailability, patients can be instructed that Desloratadine Tablets may be taken without regard to meals.Patients should be advised not to increase the dose or dosing frequency as studies have not demonstrated increased effectiveness at higher doses and somnolence may occur.Manufactured by Belcher Pharmaceuticals, LLC. 12393 Belcher Road, Suite 420 Largo, FL 33773 Rev. 12/12 PATIENT INFORMATIONDesloratadine Tablets, mgRead the Patient Information that comes with Desloratadine Tablets 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 you additional information. This leaflet does not take the place of talking to your doctor about your medical condition or treatment.What are Desloratadine TabletsDesloratadine Tablets is prescription medicine that contains the medicine desloratadine (an antihistamine).Desloratadine Tablets are used to help control the symptoms of:seasonal allergic rhinitis (sneezing, stuffy nose, runny nose and itching of the nose) in people 12 years of age and older.perennial allergic rhinitis (sneezing, stuffy nose, runny nose and itching of the nose) in people 12 years of age and older.Chronic idiopathic urticaria (long term itching) and to reduce the number and size of hives in people 12 years of age and older.Desloratadine Tablets, mg is not for children younger than 12 years of age.Who should not take Desloratadine TabletsDo not take Desloratadine tablets if you:are allergic to desloratadine or any of the ingredients in Desloratadine Tablets. See the end of this leaflet for 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 tell my doctor before taking Desloratadine TabletsBefore you take Desloratadine Tablets, 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 list of your medicines and show it to your doctor and pharmacist when you get new medicine.How should take Desloratadine TabletsTake Desloratadine Tablets exactly as your doctor tells you to take it.Do not change your dose of Desloratadine Tablets or take more often than prescribed.Desloratadine Tablets can be taken with or without food.If you take too much Desloratadine Tablets, call your doctor or get medical attention right away.What are the possible side effects of Desloratadine TabletsDesloratadine tablets may cause serious side effects, including:Allergic reactions. Stop taking Desloratadine Tablets and call your doctor right away or get emergency help if you have any of these symptoms:rashitchinghivesswelling of your lips, tongue, face, and throatshortness of breath or trouble breathingThe most common side effects of Desloratadine Tablets in adults and children 12 years of age and older with allergic rhinitis include:sore throatdry mouthmuscle paintirednesssleepinessmenstrual painIncreased sleepiness or tiredness can happen if you take more Desloratadine Tablets 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 Tablets. For more information, ask your doctor or pharmacist.Call your doctor for medical advice about side effects. You may report side effects to Belcher Pharmaceuticals LLC at 1-727-471-0850 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch How should store Desloratadine TabletsStore Desloratadine Tablets between 59F to 86F (15C to 30C).Desloratadine Tablets are sensitive to heat. Do not store above 86F (30C).Protect Desloratadine Tablets from moisture.Keep Desloratadine Tablets, and all medicines out of the reach of children.General information about Desloratadine TabletsMedicines are sometimes prescribed for purposes other than those listed in patient information leaflet. Do not use Desloratadine Tablets for condition for which it was not prescribed. Do not give Desloratadine Tablets 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 Tablets. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about Desloratadine Tablets that is written for health professionals.What are the ingredients in Desloratadine TabletsActive ingredient: DesloratadineInactive ingredients in Desloratadine Tablets: microcrystalline cellulose NF, pregelatinized starch NF, croscarmellose sodium NF, talc USP, zinc stearate, USP and FD&C Blue HT 11-14%. Manufactured by Belcher Pharmaceuticals, LLC. 12393 Belcher Road, Suite 420 Largo, FL 33773 December 2012 L05I D-0806. Patients should be instructed to use Desloratadine Tablets as directed.. As there are no food effects on bioavailability, patients can be instructed that Desloratadine Tablets may be taken without regard to meals.. Patients should be advised not to increase the dose or dosing frequency as studies have not demonstrated increased effectiveness at higher doses and somnolence may occur.. seasonal allergic rhinitis (sneezing, stuffy nose, runny nose and itching of the nose) in people 12 years of age and older.. perennial allergic rhinitis (sneezing, stuffy nose, runny nose and itching of the nose) in people 12 years of age and older.. Chronic idiopathic urticaria (long term itching) and to reduce the number and size of hives in people 12 years of age and older.. are allergic to desloratadine or any of the ingredients in Desloratadine Tablets. See the end of this leaflet for complete list of ingredients.. are allergic to loratadine (Alavert, Claritin).. 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.. ketoconazole (Nizoral). erythromycin (Ery-tab, Eryc, PCE). azithromycin (Zithromax, Zmax). antihistamines. fluoxetine (Prozac). cimetidine (Tagamet). Take Desloratadine Tablets exactly as your doctor tells you to take it.. Do not change your dose of Desloratadine Tablets or take more often than prescribed.. Desloratadine Tablets can be taken with or without food.. If you take too much Desloratadine Tablets, call your doctor or get medical attention right away.. rash. itching. hives. swelling of your lips, tongue, face, and throat. shortness of breath or trouble breathing. sore throat. dry mouth. muscle pain. tiredness. sleepiness. menstrual pain. Store Desloratadine Tablets between 59F to 86F (15C to 30C).. Desloratadine Tablets are sensitive to heat. Do not store above 86F (30C).. Protect Desloratadine Tablets from moisture.

NONCLINICAL TOXICOLOGY SECTION.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity Studies:The 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 Studies:In 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 Fertility:There was no effect on female fertility in rats at desloratadine doses up to 24 mg/kg/day (estimated desloratadine and desloratadine metabolite exposures were approximately 130 times the AUC in humans at the recommended daily oral dose). 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).. 13.2 Animal Toxicology and/or Pharmacology. Reproductive Toxicology Studies: Desloratadine was not teratogenic in rats at doses up to 48 mg/kg/day (estimated desloratadine and desloratadine metabolite exposures were approximately 210 times the AUC in humans at the recommended daily oral dose) or in rabbits at doses up to 60 mg/kg/day (estimated desloratadine exposures were approximately 230 times the AUC in humans at the recommended daily oral dose). In separate study, an increase in pre-implantation loss and decreased number of implantations and fetuses were noted in female rats at 24 mg/kg (estimated desloratadine and desloratadine metabolite exposures were approximately 120 times the AUC in humans at the recommended daily oral dose). Reduced body weight and slow righting reflex were reported in pups at doses of mg/kg/day or greater (estimated desloratadine and desloratadine metabolite exposures were approximately 50 times or greater than the AUC in humans at the recommended daily oral dose). Desloratadine had no effect on pup development at an oral dose of mg/kg/day (estimated desloratadine and desloratadine metabolite exposures were approximately times the AUC in humans at the recommended daily oral dose).

PHARMACOKINETICS SECTION.

12.3 Pharmacokinetics AbsorptionFollowing oral administration of desloratadine mg tablet once daily for 10 days to normal healthy volunteers, the mean time to maximum plasma concentrations (T max) occurred at approximately hours post dose and mean steady state peak plasma concentrations (C max) and AUC of ng/mL and 56.9 nghr/mL were observed, respectively. Neither food nor grapefruit juice had an effect on the bioavailability (C max and AUC) of desloratadine. The pharmacokinetic profile of 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 max) of Desloratadine Oral Solution. DistributionDesloratadine 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.MetabolismDesloratadine (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 15-35 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.EliminationThe mean plasma elimination half-life of desloratadine was approximately 27 hours. max 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 max and half-life values compared to desloratadine. Special PopulationsGeriatric Subjects: In older subjects (>=65 years old; n=17) following multiple-dose administration of Desloratadine Tablets, the mean max and AUC values for desloratadine were 20% greater than in younger subjects (<65 years old). The oral total body clearance (CL/F) when normalized for body weight was similar between the two age groups. The mean plasma elimination half-life of desloratadine was 33.7 hr in subjects >=65 years old. The 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 max 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 max and AUC obtained in children to 11 years of age receiving 1.25-2.5 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 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 51-69 mL/min/1.73 2), moderate (n=6; creatinine clearance 34-43 mL/min/1.73 2), and severe (n=6; creatinine clearance 5-29 mL/min/1.73 2) renal impairment or hemodialysis dependent (n=6) patients. In patients with mild and moderate renal impairment, median 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, 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 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 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 max and AUC values, respectively, compared with male subjects. The 3-hydroxydesloratadine 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 max 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 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 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 (C max and AUC 0-24 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 2Changes in Desloratadine and 3-HydroxydesloratadinePharmacokinetics in Healthy Male and Female VolunteersDesloratadine3-HydroxydesloratadineC max AUC 0-24hrs 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 4 days +15%+5%+15%+4%Fluoxetine (20 mg QD) +15%+0%+17%+13%Cimetidine (600 mg Q12h) +12%+19%-11%-3%.

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS Renal impairment: dosage adjustment is recommended 2.5, 8.6, 12.3) Hepatic impairment: dosage adjustment is recommended 2.5, 8.7, 12.3) 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 Pregnancy Category C: There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, desloratadine should be used during pregnancy only if clearly needed. Desloratadine was not teratogenic in rats or rabbits at approximately 210 and 230 times, respectively, the area under the concentration-time curve (AUC) in humans at the recommended daily oral dose. An increase in pre-implantation loss and decreased number of implantations and fetuses were noted, however, in separate study in female rats at approximately 120 times the AUC in humans at the recommended daily oral dose. Reduced body weight and slow righting reflex were reported in pups at approximately 50 times or greater than the AUC in humans at the recommended daily oral dose. Desloratadine had no effect on pup development at approximately times the AUC in humans at the recommended daily oral dose. The AUCs in comparison referred to the desloratadine exposure in rabbits and the sum of desloratadine and its metabolites exposures in rats, respectively. [See Nonclinical Toxicology 13.2).] 8.3 Nursing Mothers Desloratadine passes into breast milk; therefore, decision should be made whether to discontinue nursing or to discontinue desloratadine, taking into account the benefit of the drug to the nursing mother and the possible risk to the child.. 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 Tablets or Desloratadine Oral Solution have 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)].