Deselex

Deselex uses

• Indications and usage
• Dosage and administration
• Dosage forms and strengths
• Contraindications
• Warnings and precautions
• Adverse reactions
• Drug interactions
• Use in specific populations
• Drug abuse and dependence
• Overdosage
• Description
• Clinical pharmacology
• Nonclinical toxicology
• Clinical studies
• How supplied/storage and handling
• Patient counseling information
• Deselex reviews

1 INDICATIONS AND USAGE

Deselex Tablets are indicated for:

• Seasonal Allergic Rhinitis: relief of nasal and non-nasal symptoms in patients 12 years of age and older.
• Perennial Allergic Rhinitis: relief of nasal and non-nasal symptoms in patients 12 years 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 12 years of age and older. (1.3)

1.1 Seasonal Allergic Rhinitis

Deselex Tablets are indicated for the relief of the nasal and non-nasal symptoms of seasonal allergic rhinitis in patients 12 years of age and older.

1.2 Perennial Allergic Rhinitis

Deselex Tablets are indicated for the relief of the nasal and non-nasal symptoms of perennial allergic rhinitis in patients 12 years of age and older.

1.3 Chronic Idiopathic Urticaria

Deselex Tablets are indicated for the symptomatic relief of pruritus, reduction in the number of hives, and size of hives, in patients with chronic idiopathic urticaria 12 years of age and older.

2 DOSAGE AND ADMINISTRATION

Deselex Tablets may be taken without regard to meals.

Dosage :

Adults and adolescents 12 years of age and over:

• Deselex Tablets - one 5 mg tablet once daily

2.1 Adults and adolescents 12 years of age and over

The recommended dose of Deselex Tablets is one 5 mg tablet once daily.

2.5 Adults with Hepatic or Renal Impairment

In adult patients with liver or renal impairment, a starting dose of one 5 mg tablet every other day is recommended based on pharmacokinetic data. Dosing recommendation for children with liver or renal impairment cannot be made due to lack of data [see Clinical Pharmacology (12.3) ].

3 DOSAGE FORMS AND STRENGTHS

Deselex Tablets are light blue round tablets debossed with "5" containing 5 mg Deselex.

• Deselex Tablets - 5 mg (3)

4 CONTRAINDICATIONS

Deselex Tablets are 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)

5 WARNINGS AND PRECAUTIONS

• Hypersensitivity reactions including rash, pruritus, urticaria, edema, dyspnea, and anaphylaxis have been reported. In such cases, stop Deselex Tablets at once and consider alternative treatments.

5.1 Hypersensitivity Reactions

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

6 ADVERSE REACTIONS

The following adverse reactions are discussed in greater detail in other sections of the label:

• Hypersensitivity reactions. [See Warnings and Precautions .]

• 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 Virtus Pharmaceuticals at 813-283-1344 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 Deselex 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 Deselex and placebo-treated patients. The percent of patients who withdrew prematurely due to adverse events was 2.4% in the Deselex group and 2.6% in the placebo group. There were no serious adverse events in these trials in patients receiving Deselex. All adverse events that were reported by greater than or equal to 2% of patients who received the recommended daily dose of Deselex Tablets (5 mg once daily), and that were more common with Deselex Tablets than placebo, are listed in Table 1.

The frequency and magnitude of laboratory and electrocardiographic abnormalities were similar in Deselex 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 Deselex Tablets and 205 received placebo. Adverse events that were reported by greater than or equal to 2% of patients who received Deselex Tablets and that were more common with Deselex than placebo were (rates for Deselex 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 Deselex 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 Deselex and placebo in at least 2 percent of subjects receiving Deselex 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 Deselex product and placebo in at least 2 percent of subjects receiving Deselex Oral Solution and at a frequency greater than placebo were fever (16.9%, 12.9%), diarrhea (15.4%, 11.3%), upper respiratory tract infections (10.8%, 9.7%), coughing (10.8%, 6.5%), appetite increased (3.1%, 1.6%), emotional lability (3.1%, 0%), epistaxis (3.1%, 0%), parasitic infection (3.1%, 0%), pharyngitis (3.1%, 0%), rash maculopapular (3.1%, 0%).

In subjects 6 months to 11 months of age, adverse events reported for Deselex and placebo in at least 2 percent of subjects receiving Deselex Oral Solution and at a frequency greater than placebo were upper respiratory tract infections (21.2%, 12.9%), diarrhea (19.7%, 8.1%), fever (12.1%, 1.6%), irritability (12.1%, 11.3%), coughing (10.6%, 9.7%), somnolence (9.1%, 8.1%), bronchitis (6.1%, 0%), otitis media (6.1%, 1.6%), vomiting (6.1%, 3.2%), anorexia (4.5%, 1.6%), pharyngitis (4.5%, 1.6%), insomnia (4.5%, 0%), rhinorrhea (4.5%, 3.2%), erythema (3.0%, 1.6%), and nausea (3.0%, 0%). There were no clinically meaningful changes in any electrocardiographic parameter, including the QTc interval. Only one of the 246 pediatric subjects receiving Deselex 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 a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The following spontaneous adverse events have been reported during the marketing of Deselex: 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.

7 DRUG INTERACTIONS

7.1 Inhibitors of Cytochrome P450 3A4

In controlled clinical studies co-administration of Deselex with ketoconazole, erythromycin, or azithromycin resulted in increased plasma concentrations of Deselex and 3 hydroxydesloratadine, but there were no clinically relevant changes in the safety profile of Deselex. [See Clinical Pharmacology .]

7.2 Fluoxetine

In controlled clinical studies co-administration of Deselex with fluoxetine, a selective serotonin reuptake inhibitor (SSRI), resulted in increased plasma concentrations of Deselex and 3 hydroxydesloratadine, but there were no clinically relevant changes in the safety profile of Deselex. [See Clinical Pharmacology (12.3) .]

7.3 Cimetidine

In controlled clinical studies co-administration of Deselex with cimetidine, a histamine H₂-receptor antagonist, resulted in increased plasma concentrations of Deselex and 3 hydroxydesloratadine, but there were no clinically relevant changes in the safety profile of Deselex. [See Clinical Pharmacology (12.3).]

8 USE IN SPECIFIC POPULATIONS

• Renal impairment: dosage adjustment is recommended
• 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, Deselex should be used during pregnancy only if clearly needed. Deselex 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 a decreased number of implantations and fetuses were noted, however, in a 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. Deselex had no effect on pup development at approximately 7 times the AUC in humans at the recommended daily oral dose. The AUCs in comparison referred to the Deselex exposure in rabbits and the sum of Deselex and its metabolites exposures in rats, respectively. [See Nonclinical Toxicology (13.2).]

8.3 Nursing Mothers

Deselex passes into breast milk; therefore, a decision should be made whether to discontinue nursing or to discontinue Deselex, 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 Deselex Oral Solution in the pediatric population is based on cross-study comparison of the plasma concentration of Deselex in adults and pediatric subjects. The safety of Deselex Oral Solution has been established in 246 pediatric subjects aged 6 months to 11 years in three placebo-controlled clinical studies. Since the course of seasonal and perennial allergic rhinitis and chronic idiopathic urticaria and the effects of Deselex are sufficiently similar in the pediatric and adult populations, it allows extrapolation from the adult efficacy data to pediatric patients. The effectiveness of Deselex Oral Solution in these age groups is supported by evidence from adequate and well-controlled studies of Deselex Tablets in adults. The safety and effectiveness of Deselex Tablets or Deselex Oral Solution have not been demonstrated in pediatric patients less than 6 months of age. [See Clinical Pharmacology.]

8.5 Geriatric Use

Clinical studies of Deselex 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 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) ].

9 DRUG ABUSE AND DEPENDENCE

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

10 OVERDOSAGE

In the event of overdose, consider standard measures to remove any unabsorbed drug. Symptomatic and supportive treatment is recommended. Deselex 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 Deselex product. In a 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 Deselex 45 mg for 10 days [see Clinical Pharmacology (12.2) ].

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

11 DESCRIPTION

Deselex Tablets are light blue, round, tablets containing 5 mg Deselex, an antihistamine, to be administered orally. Deselex Tablets also contain the following inactive ingredients: microcrystalline cellulose NF, pregelatinized starch NF, croscarmellose sodium NF, talc USP, zinc stearate, USP and FD&C Blue #2 HT 11-14%.

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

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Deselex is a long-acting tricyclic histamine antagonist with selective H₁-receptor histamine antagonist activity. Receptor binding data indicates that at a concentration of 2-3 ng/mL, Deselex shows significant interaction with the human histamine H₁-receptor. Deselex inhibited histamine release from human mast cells in vitro. Results of a radiolabeled tissue distribution study in rats and a radioligand H₁-receptor binding study in guinea pigs showed that Deselex 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 Deselex have shown that the drug exhibits an antihistaminic effect by 1 hour; this activity may persist for as long as 24 hours. There was no evidence of histamine-induced skin wheal tachyphylaxis within the Deselex 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 a blinded fashion by a cardiologist. In Deselex - treated subjects, there was an increase in mean heart rate of 9.2 bpm relative to placebo. The QT interval was corrected for heart rate (QTc) by both the Bazett and Fridericia methods. Using the QTc (Bazett) there was a mean increase of 8.1 msec in Desloratadine-treated subjects relative to placebo. Using QTc (Fridericia) there was a mean increase of 0.4 msec in Deselex treated subjects relative to placebo. No clinically relevant adverse events were reported.

12.3 Pharmacokinetics

Absorption

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

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

Distribution

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

Metabolism

Deselex (a major metabolite of loratadine) is extensively metabolized to 3-hydroxydesloratadine, an active metabolite, which is subsequently glucuronidated. The enzyme(s) responsible for the formation of 3-hydroxydesloratadine have not been identified. Data from clinical trials indicate that a subset of the general population has a decreased ability to form 3-hydroxydesloratadine, and are poor metabolizers of Deselex. In pharmacokinetic studies (n=3,748), approximately 6% of subjects were poor metabolizers of Deselex (defined as a subject with an AUC ratio of 3-hydroxydesloratadine to Deselex less than 0.1, or a subject with a Deselex half-life exceeding 50 hours). These pharmacokinetic studies included subjects between the ages of 2 and 70 years, including 977 subjects aged 2 to 5 years, 1,575 subjects aged 6 to 11 years, and 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 Deselex in the poor metabolizers was approximately 6-fold greater than in the subjects who are not poor metabolizers. Subjects who are poor metabolizers of Deselex cannot be prospectively identified and will be exposed to higher levels of Deselex following dosing with the recommended dose of Deselex. In multidose clinical safety studies, where metabolizer status was identified, a total of 94 poor metabolizers and 123 normal metabolizers were enrolled and treated with Deselex 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.

Elimination

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

Special Populations

Geriatric Subjects: In older subjects (≥65 years old; n=17) following multiple-dose administration of Deselex Tablets, the mean C_max and AUC values for Deselex 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 Deselex 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 6 to 11 years old, a single dose of 5 mL of Deselex Oral solution containing 2.5 mg of Deselex, resulted in Deselex plasma concentrations similar to those achieved in adults administered a single 5 mg Deselex Tablet. In subjects 2 to 5 years old, a single dose of 2.5 mL of Deselex Oral solution containing 1.25 mg of Deselex, resulted in Deselex plasma concentrations similar to those achieved in adults administered a single 5-mg Deselex Tablet. However, the C_max and AUC of the metabolite (3-hydroxydesloratadine) were 1.27 and 1.61 times higher for the 5 mg dose of Oral solution administered in adults compared to the C_max and AUC obtained in children 2 to 11 years of age receiving 1.25-2.5 mg of Deselex Oral solution. A single dose of either 2.5 mL or 1.25 mL of Deselex Oral solution containing 1.25 mg or 0.625 mg, respectively, of Deselex was administered to subjects 6 to 11 months of age and 12 to 23 months of age. The results of a population pharmacokinetic analysis indicated that a dose of 1 mg for subjects aged 6 to 11 months and 1.25 mg for subjects 12 to 23 months of age is required to obtain Deselex plasma concentrations similar to those achieved in adults administered a single 5 mg dose of Deselex Oral solution.

Renally Impaired: Deselex pharmacokinetics following a single dose of 7.5 mg were characterized in patients with mild (n=7; creatinine clearance 51-69 mL/min/1.73 m²), moderate (n=6; creatinine clearance 34-43 mL/min/1.73 m²), and severe (n=6; creatinine clearance 5-29 mL/min/1.73 m²) renal impairment or hemodialysis dependent (n=6) patients. In patients with mild and moderate renal impairment, median C_max and AUC values increased by approximately 1.2- and 1.9-fold, respectively, relative to subjects with normal renal function. In patients with severe renal impairment or who were hemodialysis dependent, C_max and AUC values increased by approximately 1.7- and 2.5-fold, respectively. Minimal changes in 3-hydroxydesloratadine concentrations were observed. Deselex and 3-hydroxydesloratadine were poorly removed by hemodialysis. Plasma protein binding of Deselex 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: Deselex pharmacokinetics were characterized following a single oral dose in patients with mild (n=4), moderate (n=4), and severe (n=4) hepatic impairment as defined by the Child-Pugh classification of hepatic function and 8 subjects with normal hepatic function. Patients with hepatic impairment, regardless of severity, had approximately a 2.4-fold increase in AUC as compared with normal subjects. The apparent oral clearance of Deselex 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 Deselex in patients with hepatic impairment was observed. For 3-hydroxydesloratadine, the mean C_max and AUC values for patients with hepatic impairment were not statistically significantly different from subjects with normal hepatic function. Dosage adjustment for patients with hepatic impairment is recommended [see Dosage and Administration (2.5) ].

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

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

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

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity Studies:

The carcinogenic potential of Deselex was assessed using a loratadine study in rats and a Deselex study in mice. In a 2-year study in rats, loratadine was administered in the diet at doses up to 25 mg/kg/day. A 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 Deselex and Deselex metabolite exposures in rats given 10 mg/kg of loratadine were approximately 7 times the AUC in humans at the recommended daily oral dose. The clinical significance of these findings during long-term use of Deselex is not known.

In a 2-year dietary study in mice, males and females given up to 16 mg/kg/day and 32 mg/kg/day Deselex, respectively, did not show significant increases in the incidence of any tumors. The estimated Deselex and Deselex 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 Deselex, there was no evidence of genotoxic potential in a reverse mutation assay (Salmonella/E. coli mammalian microsome bacterial mutagenicity assay) or in 2 assays for chromosomal aberrations (human peripheral blood lymphocyte clastogenicity assay and mouse bone marrow micronucleus assay).

Impairment of Fertility:

There was no effect on female fertility in rats at Deselex doses up to 24 mg/kg/day (estimated Deselex and Deselex 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 Deselex dose of 12 mg/kg in rats (estimated Deselex and Deselex metabolite exposures were approximately 45 times the AUC in humans at the recommended daily oral dose). Deselex had no effect on fertility in rats at an oral dose of 3 mg/kg/day (estimated Deselex and Deselex metabolite exposures were approximately 8 times the AUC in humans at the recommended daily oral dose).

13.2 Animal Toxicology and/or Pharmacology

Reproductive Toxicology Studies:

Deselex was not teratogenic in rats at doses up to 48 mg/kg/day (estimated Deselex and Deselex 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 Deselex exposures were approximately 230 times the AUC in humans at the recommended daily oral dose). In a separate study, an increase in pre-implantation loss and a decreased number of implantations and fetuses were noted in female rats at 24 mg/kg (estimated Deselex and Deselex metabolite exposures were approximately 120 times the AUC in humans at the recommended daily oral dose). Reduced body weight and slow righting reflex were reported in pups at doses of 9 mg/kg/day or greater (estimated Deselex and Deselex metabolite exposures were approximately 50 times or greater than the AUC in humans at the recommended daily oral dose). Deselex had no effect on pup development at an oral dose of 3 mg/kg/day (estimated Deselex and Deselex metabolite exposures were approximately 7 times the AUC in humans at the recommended daily oral dose).

14 CLINICAL STUDIES

14.1 Seasonal Allergic Rhinitis

The clinical efficacy and safety of Deselex 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 Deselex in 4 double-blind, randomized, placebo-controlled clinical trials of 2 to 4 weeks' duration conducted in the United States. The results of these studies demonstrated the efficacy and safety of Deselex 5 mg in the treatment of adult and adolescent patients with seasonal allergic rhinitis. In a dose-ranging trial, Deselex 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, 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, Deselex Tablets 5 mg once daily improved rhinitis symptoms, with no decrease in pulmonary function. This supports the safety of administering Deselex Tablets to adult patients with seasonal allergic rhinitis with mild to moderate asthma.

Deselex Tablets 5 mg once daily significantly reduced the Total Symptom Score (the sum of individual scores of nasal and non-nasal symptoms) in patients with seasonal allergic rhinitis. See Table 3.

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

14.2 Perennial Allergic Rhinitis

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

14.3 Chronic Idiopathic Urticaria

The efficacy and safety of Deselex Tablets 5 mg once daily was studied in 416 chronic idiopathic urticaria patients 12 to 84 years of age, of whom 211 received Deselex. In two double-blind, placebo-controlled, randomized clinical trials of six weeks duration, at the pre-specified one-week primary time point evaluation, Deselex 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 Deselex Tablets 5 mg reduced the secondary endpoints, "Number of Hives" and the "Size of the Largest Hive," when compared to placebo.

16 HOW SUPPLIED/STORAGE AND HANDLING

Deselex Tablets: Debossed "5", light blue, round tablets that are packaged in high-density polyethylene plastic bottles of 30 (NDC 76439-107-30), 100 (NDC 76439-0107-10) and 500 (NDC 76439-107-50).

Storage:

• Deselex Tablets: Store at 25° C (77° F); excursions permitted to 15° C - 30° C (59° F - 86° F) Heat sensitive. Avoid exposure at or above 30° C (86° F).
  

  Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.

17 PATIENT COUNSELING INFORMATION

.

17.1 Information for Patients

• Patients should be instructed to use Deselex Tablets as directed.
• As there are no food effects on bioavailability, patients can be instructed that Deselex 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

Manufactured for:

Virtus Pharmaceuticals

Tampa, FL 33619

www.virtusRX.com

MADE IN USA

Rev. 04/12

PATIENT INFORMATION

Deselex Tablets, 5 mg

Read the Patient Information that comes with Deselex tablets before you start taking it and each time you get a refill. There may be new information. This leaflet is a 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 Deselex tablets?

Deselex tablets are a prescription medicine that contains the medicine Deselex (an antihistamine).

Deselex 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.

Deselex Tablets, 5 mg is not for children younger than 12 years of age.

Who should not take Deselex tablets?

Do not take Deselex tablets if you:

• are allergic to Deselex or any of the ingredients in Deselex Tablets. See the end of this leaflet for a complete list of ingredients.
• are allergic to loratadine (Alavert, Claritin).

Talk to your doctor before taking this medicine if you have any questions about whether or not to take this medicine.

What should I tell my doctor before taking Deselex tablets?

Before you take Deselex 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 Deselex 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. Deselex can pass into your breast milk.

Talk to your doctor about the best way to feed your baby if you take Deselex tablets.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins and herbal supplements. Deselex may affect the way other medicines work, and other medicines may affect how Deselex works. Especially tell your doctor if you take:

• ketoconazole (Nizoral)
• erythromycin (Ery-tab, Eryc, PCE)
• azithromycin (Zithromax, Zmax)
• antihistamines
• fluoxetine (Prozac)
• cimetidine (Tagamet)

Know the medicines you take. Keep a list of your medicines and show it to your doctor and pharmacist when you get a new medicine.

How should I take Deselex Tablets?

• Take Deselex tablets exactly as your doctor tells you to take it.
• Do not change your dose of Deselex tablets or take more often than prescribed.
• Deselex tablets can be taken with or without food.
• If you take too much Deselex tablets, call your doctor or get medical attention right away.

What are the possible side effects of Deselex Tablets?

Deselex tablets may cause serious side effects, including:

Allergic reactions. Stop taking Deselex tablets and call your doctor right away or get emergency help if you have any of these symptoms:

• rash
• itching
• hives
• swelling of your lips, tongue, face, and throat
• shortness of breath or trouble breathing

The most common side effects of Deselex tablets in adults and children 12 years of age and older with allergic rhinitis include:

• sore throat
• dry mouth
• muscle pain
• tiredness
• sleepiness
• menstrual pain

Increased sleepiness or tiredness can happen if you take more Deselex 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 Deselex Tablets. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to Virtus Pharmaceuticals at 813-283-1344 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

How should I store Deselex Tablets?

• Store Deselex Tablets between 59°F to 86°F (15°C to 30°C).
• Deselex Tablets are sensitive to heat. Do not store above 86°F (30°C).
• Protect Deselex Tablets from moisture.

Keep Deselex Tablets, and all medicines out of the reach of children.

General information about Deselex Tablets

Medicines are sometimes prescribed for purposes other than those listed in a patient information leaflet. Do not use Deselex Tablets for a condition for which it was not prescribed. Do not give Deselex 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 Deselex tablets. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about Deselex Tablets that is written for health professionals.

What are the ingredients in Deselex Tablets?

Active ingredient: Deselex

Inactive ingredients in Deselex Tablets: microcrystalline cellulose NF, pregelatinized starch NF, croscarmellose sodium NF, talc USP, zinc stearate, USP and FD&C Blue #2 HT 11-14%.

Manufactured by

Belcher Pharmaceuticals, LLC.

12393 Belcher Road, Suite 420

Largo, FL 33773

Manufactured for:

Virtus Pharmaceuticals

Tampa, FL 33619

www.virtusRX.com

MADE IN USA

April 2012

L05I-VIR

R-1204

Deselex 5mg tablet

Chemical Structure

Deselex pharmaceutical active ingredients containing related brand and generic drugs:

• Desloratadine

Deselex available forms, composition, doses:

• N/A

Deselex destination | category:

• Human:
• Antihistamines and antiallergics

Deselex Anatomical Therapeutic Chemical codes:

• R06AX27 - Desloratadine

Deselex pharmaceutical companies:

• Schering-Plough

References

1. Dailymed."DESLORATADINE TABLET [BRYANT RANCH PREPACK]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
2. Dailymed."DESLORATADINE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
3. "Desloratadine". https://pubchem.ncbi.nlm.nih.gov/co... (accessed August 28, 2018).

Frequently asked Questions

Depending on the reaction of the Deselex after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Deselex not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

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The information was verified by Dr. Rachana Salvi, MD Pharmacology