Desloratadine Oral Solution

1 INDICATIONS AND USAGE Desloratadine Oral Solution is a histamine-1 (H1) receptor antagonist indicated for: Seasonal Allergic Rhinitis: relief of nasal and non-nasal symptoms in patients 2 years of age and older. (1.1) Perennial Allergic Rhinitis: relief of nasal and non-nasal symptoms in patients 6 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 6 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 2 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 6 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 6 months of age and older. 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 2 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 6 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 6 months of age and older.

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 a commercially available measuring dropper or syringe that is calibrated to deliver 2 mL and 2.5 mL (½ teaspoon). Dosage (by age): Adults and Adolescents 12 Years of Age and Over: 2 teaspoonfuls (5 mg in 10 mL) once daily (2) Children 6 to 11 Years of Age: 1 teaspoonful (2.5 mg in 5 mL) once daily Children 12 Months to 5 Years of Age: ½ 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 2 teaspoonfuls (5 mg in 10 mL) once daily. 2.2 Children 6 to 11 Years of Age The recommended dose of desloratadine oral solution is 1 teaspoonful (2.5 mg in 5 mL) once daily. 2.3 Children 12 Months to 5 Years of Age The recommended dose of desloratadine oral solution is ½ teaspoonful (1.25 mg in 2.5 mL) once daily. 2.4 Children 6 to 11 Months of Age The recommended dose of desloratadine oral solution is 2 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)]. 2.1 Adults and Adolescents 12 Years of Age and Over The recommended dose of desloratadine oral solution is 2 teaspoonfuls (5 mg in 10 mL) once daily. 2.2 Children 6 to 11 Years of Age The recommended dose of desloratadine oral solution is 1 teaspoonful (2.5 mg in 5 mL) once daily. 2.3 Children 12 Months to 5 Years of Age The recommended dose of desloratadine oral solution is ½ teaspoonful (1.25 mg in 2.5 mL) once daily. 2.4 Children 6 to 11 Months of Age The recommended dose of desloratadine oral solution is 2 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)].

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) 5.1 Hypersensitivity Reactions Hypersensitivity reactions including rash, pruritus, urticaria, edema, dyspnea, and anaphylaxis have been reported after administration of desloratadine. If such a reaction occurs, therapy with desloratadine should be stopped and alternative treatment should be considered. [See Adverse Reactions (6.2).] 5.1 Hypersensitivity Reactions Hypersensitivity reactions including rash, pruritus, urticaria, edema, dyspnea, and anaphylaxis have been reported after administration of desloratadine. If such a reaction occurs, therapy with desloratadine should be stopped and alternative treatment should be considered. [See Adverse Reactions (6.2).]

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)]. • Hypersensitivity (4, 6.2)

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 3 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, a selective serotonin reuptake inhibitor (SSRI), resulted in increased plasma concentrations of desloratadine and 3 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, a histamine H2-receptor antagonist, resulted in increased plasma concentrations of desloratadine and 3 hydroxydesloratadine, but there were no clinically relevant changes in the safety profile of desloratadine. [See Clinical Pharmacology (12.3).] 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 3 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, a selective serotonin reuptake inhibitor (SSRI), resulted in increased plasma concentrations of desloratadine and 3 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, a histamine H2-receptor antagonist, resulted in increased plasma concentrations of desloratadine and 3 hydroxydesloratadine, but there were no clinically relevant changes in the safety profile of desloratadine. [See Clinical Pharmacology (12.3).]

8.1 Pregnancy Risk Summary The limited available data with desloratadine in pregnant women are not sufficient to inform a 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 5 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 2 to 4% and 15 to 20%, respectively. Data Animal Data Desloratadine was given orally during organogenesis to pregnant rats at doses of 6, 24 and 48 mg/kg/day (approximately 50, 200 and 320 times the summed AUC-based exposure of desloratadine and its metabolite at the RHD). No fetal malformations were present. Reduced fetal weights and skeletal variations noted at doses of 24 and 48 mg/kg/day were likely secondary to the maternal toxicities of reduced body weight gain and food consumption observed at the same doses. Desloratadine was also given orally during organogenesis to pregnant rabbits at doses of 15, 30 and 60 mg/kg/day (approximately 30, 70 and 230 times the AUC-based exposure of desloratadine at the RHD). No adverse effects to the fetus were noted. Reduced maternal body weight gain was noted in rabbits at 60 mg/kg/day. In a peri-and post-natal development study, desloratadine was given to rats orally during the perinatal (Gestation Day 6) through lactation periods (Postpartum Day 21) at doses of 3, 9 and 18 mg/kg/day. Reduced body weight and slow righting reflex were reported in F1 pups at doses of 9 mg/kg/day or greater (approximately 70 times or greater than the summed AUC-based exposure of desloratadine and its metabolite at the RHD). Desloratadine had no effect on F1 pup development at 3 mg/kg/day (approximately 10 times the summed AUC-based exposure of desloratadine and its metabolite at the RHD). Maternal toxicities including reduced body weight gain and food consumption were noted at 18 mg/kg/day for F0 dams. F1 offspring were subsequently mated and there was no developmental toxicity for F2 pups observed.

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 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. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a 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 Adolescents Allergic 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 5 mg. In patients receiving 5 mg daily, the rate of adverse events was similar between desloratadine and placebo-treated patients. The percent of patients who withdrew prematurely due to adverse events was 2.4% in the desloratadine group and 2.6% in the placebo group. There were no serious adverse events in these trials in patients receiving desloratadine. All adverse events that were reported by greater than or equal to 2% of patients who received the recommended daily dose of desloratadine tablets (5 mg once daily), and that were more common with desloratadine tablets than placebo, are listed in Table 1. Table 1: Incidence of Adverse Events Reported by ≥ 2% of Adult and Adolescent Allergic Rhinitis Patients Receiving Desloratadine Tablets Adverse Event Desloratadine Tablets 5 mg (n = 1,655) Placebo (n = 1,652) Infections and Infestations Pharyngitis 4.1% 2% Nervous System Disorders Somnolence 2.1% 1.8% Gastrointestinal Disorders Dry Mouth 3% 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%). Pediatrics Two hundred and forty-six pediatric subjects 6 months to 11 years of age received desloratadine oral solution for 15 days in three placebo-controlled clinical trials. Pediatric subjects aged 6 to 11 years received 2.5 mg once a day, subjects aged 1 to 5 years received 1.25 mg once a day, and subjects 6 to 11 months of age received 1.0 mg once a day. In subjects 6 to 11 years of age, no individual adverse event was reported by 2 percent or more of the subjects. In subjects 2 to 5 years of age, adverse events reported for desloratadine and placebo in at least 2 percent of subjects receiving desloratadine oral solution and at a frequency greater than placebo were fever (5.5%, 5.4%), urinary tract infection (3.6%, 0%) and varicella (3.6%, 0%). In subjects 12 months to 23 months of age, adverse events reported for the desloratadine product and placebo in at least 2 percent of subjects receiving desl…