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Dilora

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Dilora uses


1 INDICATIONS AND USAGE

Dilora Tablets are indicated for:

1.1 Seasonal Allergic Rhinitis

Dilora 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

Dilora 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

Dilora 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

Dilora Tablets may be taken without regard to meals.

Dosage :

Adults and adolescents 12 years of age and over:

2.1 Adults and adolescents 12 years of age and over

The recommended dose of Dilora 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) ].

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3 DOSAGE FORMS AND STRENGTHS

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

4 CONTRAINDICATIONS

Dilora 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) ].

5 WARNINGS AND PRECAUTIONS

5.1 Hypersensitivity Reactions

Hypersensitivity reactions including rash, pruritus, urticaria, edema, dyspnea, and anaphylaxis have been reported after administration of Dilora. If such a reaction occurs, therapy with Dilora 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:


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

Adverse Event Dilora Tablets 5 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 Dilora 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 Dilora Tablets and 205 received placebo. Adverse events that were reported by greater than or equal to 2% of patients who received Dilora Tablets and that were more common with Dilora than placebo were (rates for Dilora 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 Dilora 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 Dilora and placebo in at least 2 percent of subjects receiving Dilora 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 Dilora product and placebo in at least 2 percent of subjects receiving Dilora 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 Dilora and placebo in at least 2 percent of subjects receiving Dilora 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 Dilora 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 Dilora: 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.

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7 DRUG INTERACTIONS

7.1 Inhibitors of Cytochrome P450 3A4

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

7.2 Fluoxetine

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

7.3 Cimetidine

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

8 USE IN SPECIFIC POPULATIONS

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, Dilora should be used during pregnancy only if clearly needed. Dilora 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. Dilora 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 Dilora exposure in rabbits and the sum of Dilora and its metabolites exposures in rats, respectively. [See Nonclinical Toxicology (13.2).]

8.3 Nursing Mothers

Dilora passes into breast milk; therefore, a decision should be made whether to discontinue nursing or to discontinue Dilora, 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 Dilora Oral Solution in the pediatric population is based on cross-study comparison of the plasma concentration of Dilora in adults and pediatric subjects. The safety of Dilora 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 Dilora are sufficiently similar in the pediatric and adult populations, it allows extrapolation from the adult efficacy data to pediatric patients. The effectiveness of Dilora Oral Solution in these age groups is supported by evidence from adequate and well-controlled studies of Dilora Tablets in adults. The safety and effectiveness of Dilora Tablets or Dilora 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 Dilora 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) ].

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9 DRUG ABUSE AND DEPENDENCE

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

10 OVERDOSAGE

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

Lethality occurred in rats at oral doses of 250 mg/kg or greater (estimated Dilora and Dilora 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 Dilora 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 Dilora exposures were approximately 810 times the human daily oral dose on a mg/m2 basis).

11 DESCRIPTION

Dilora Tablets are light blue, round, tablets containing 5 mg Dilora, an antihistamine, to be administered orally. Dilora 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%.

Dilora 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:

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12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Dilora 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, Dilora shows significant interaction with the human histamine H1-receptor. Dilora 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 Dilora 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 Dilora 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 Dilora 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 Dilora - 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 Dilora treated subjects relative to placebo. No clinically relevant adverse events were reported.

12.3 Pharmacokinetics

Absorption

Following oral administration of a Dilora 5 mg tablet once daily for 10 days to normal healthy volunteers, the mean time to maximum plasma concentrations (Tmax) occurred at approximately 3 hours post dose and mean steady state peak plasma concentrations (Cmax) 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 (Cmax and AUC) of Dilora.

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

Distribution

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

Metabolism

Dilora (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 Dilora. In pharmacokinetic studies (n=3,748), approximately 6% of subjects were poor metabolizers of Dilora (defined as a subject with an AUC ratio of 3-hydroxydesloratadine to Dilora less than 0.1, or a subject with a Dilora 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 Dilora in the poor metabolizers was approximately 6-fold greater than in the subjects who are not poor metabolizers. Subjects who are poor metabolizers of Dilora cannot be prospectively identified and will be exposed to higher levels of Dilora following dosing with the recommended dose of Dilora. 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 Dilora 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 Dilora was approximately 27 hours. Cmax 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 Tmax and half-life values compared to Dilora.

Special Populations

Geriatric Subjects: In older subjects (≥65 years old; n=17) following multiple-dose administration of Dilora Tablets, the mean Cmax and AUC values for Dilora 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 Dilora 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 Dilora Oral solution containing 2.5 mg of Dilora, resulted in Dilora plasma concentrations similar to those achieved in adults administered a single 5 mg Dilora Tablet. In subjects 2 to 5 years old, a single dose of 2.5 mL of Dilora Oral solution containing 1.25 mg of Dilora, resulted in Dilora plasma concentrations similar to those achieved in adults administered a single 5-mg Dilora Tablet. However, the Cmax 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 Cmax and AUC obtained in children 2 to 11 years of age receiving 1.25-2.5 mg of Dilora Oral solution. A single dose of either 2.5 mL or 1.25 mL of Dilora Oral solution containing 1.25 mg or 0.625 mg, respectively, of Dilora 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 Dilora plasma concentrations similar to those achieved in adults administered a single 5 mg dose of Dilora Oral solution.

Renally Impaired: Dilora 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 Cmax and AUC values increased by approximately 1.2- and 1.9-fold, respectively, relative to subjects with normal renal function. In patients with severe renal impairment or who were hemodialysis dependent, Cmax and AUC values increased by approximately 1.7- and 2.5-fold, respectively. Minimal changes in 3-hydroxydesloratadine concentrations were observed. Dilora and 3-hydroxydesloratadine were poorly removed by hemodialysis. Plasma protein binding of Dilora 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: Dilora 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 Dilora 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 Dilora in patients with hepatic impairment was observed. For 3-hydroxydesloratadine, the mean Cmax and AUC values for patients with hepatic impairment were not statistically significantly different from subjects with normal hepatic function. Dosage adjustment for patients with hepatic impairment is recommended [see Dosage and Administration (2.5) ].

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

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

Drug Interactions: In two controlled crossover clinical pharmacology studies in healthy male (n=12 in each study) and female (n=12 in each study) volunteers, Dilora 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, Dilora 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 (Cmax and AUC 0-24 hrs) of Dilora and 3-hydroxydesloratadine were observed, there were no clinically relevant changes in the safety profile of Dilora, as assessed by electrocardiographic parameters (including the corrected QT interval), clinical laboratory tests, vital signs, and adverse events.

Dilora 3-Hydroxydesloratadine
Cmax AUC

0-24hrs

 Cmax 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%

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity Studies:

The carcinogenic potential of Dilora was assessed using a loratadine study in rats and a Dilora 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 Dilora and Dilora 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 Dilora 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 Dilora, respectively, did not show significant increases in the incidence of any tumors. The estimated Dilora and Dilora 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 Dilora, 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 Dilora doses up to 24 mg/kg/day (estimated Dilora and Dilora 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 Dilora dose of 12 mg/kg in rats (estimated Dilora and Dilora metabolite exposures were approximately 45 times the AUC in humans at the recommended daily oral dose). Dilora had no effect on fertility in rats at an oral dose of 3 mg/kg/day (estimated Dilora and Dilora 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:

Dilora was not teratogenic in rats at doses up to 48 mg/kg/day (estimated Dilora and Dilora 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 Dilora 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 Dilora and Dilora 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 Dilora and Dilora metabolite exposures were approximately 50 times or greater than the AUC in humans at the recommended daily oral dose). Dilora had no effect on pup development at an oral dose of 3 mg/kg/day (estimated Dilora and Dilora 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 Dilora 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 Dilora 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 Dilora 5 mg in the treatment of adult and adolescent patients with seasonal allergic rhinitis. In a dose-ranging trial, Dilora 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, Dilora Tablets 5 mg once daily improved rhinitis symptoms, with no decrease in pulmonary function. This supports the safety of administering Dilora Tablets to adult patients with seasonal allergic rhinitis with mild to moderate asthma.

Dilora 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.

Treatment Group

(n)

 Mean BaselineAt baseline, a total nasal symptom score (sum of 4 individual symptoms) of at least 6 and a total non-nasal symptom score (sum of 4 individual symptoms) of at least 5 (each symptom scored 0 to 3 where 0=no symptom and 3=severe symptoms) was required for trial eligibility. TSS ranges from 0=no symptoms to 24=maximal symptoms.

(SEM)

 Change from BaselineMean reduction in TSS averaged over the 2 - week treatment period.

(SEM)

 Placebo Comparison

(P-value)
SEM = Standard Error of the Mean
Dilora

5.0 mg (171)

 14.2 (0.3) -4.3 (0.3) P<0.01
Placebo (173) 13.7 (0.3) -2.5 (0.3)

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

14.2 Perennial Allergic Rhinitis

The clinical efficacy and safety of Dilora 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 Dilora 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 Dilora Tablets 5 mg once daily was shown to significantly reduce the Total Symptom Score in patients with perennial allergic rhinitis (Table 4).

Treatment Group

(n)

 Mean BaselineAt baseline, average of total symptom score (sum of 5 individual nasal symptoms and 3 non-nasal symptoms, each symptom scored 0 to 3 where 0=no symptom and 3=severe symptoms) of at least 10 was required for trial eligibility. TSS ranges from 0=no symptoms to 24=maximal symptoms.

(SEM)

 Change from BaselineMean reduction in TSS averaged over the 4 week treatment period.

(SEM)

 Placebo Comparison

(P-value)
SEM = Standard Error of the Mean
Dilora

5.0 mg (337)

 12.37 (0.18) -4.06 (0.21) P=0.01
Placebo (337) 12.30 (0.18) -3.27 (0.21)

14.3 Chronic Idiopathic Urticaria

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

Treatment Group

(n)

 Mean Baselinex

(SEM)

 Change from BaselineMean reduction in Pruritus averaged over the first week of treatment.

(SEM)

 Placebo Comparison

(P-value)
Pruritus scored 0 to 3 where 0=no symptom to 3=maximum symptom
SEM = Standard Error of the Mean
Dilora

5.0 mg (115)

 2.19 (0.04) -1.05 (0.07) P=0.01
Placebo (110) 2.21 (0.04) -0.52 (0.07)

16 HOW SUPPLIED/STORAGE AND HANDLING

Dilora 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:

17 PATIENT COUNSELING INFORMATION

.

17.1 Information for Patients


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

Dilora Tablets, 5 mg

Read the Patient Information that comes with Dilora 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 Dilora tablets?

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

Dilora tablets are used to help control the symptoms of:


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

Who should not take Dilora tablets?

Do not take Dilora tablets if you:


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 Dilora tablets?

Before you take Dilora Tablets, tell your doctor if you:


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

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


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 Dilora Tablets?


What are the possible side effects of Dilora Tablets?

Dilora tablets may cause serious side effects, including:

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


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


Increased sleepiness or tiredness can happen if you take more Dilora 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 Dilora 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 Dilora Tablets?


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

General information about Dilora Tablets

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

What are the ingredients in Dilora Tablets?

Active ingredient: Dilora

Inactive ingredients in Dilora 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

Dilora 5mg tablet

Chemical Structure

Dilora pharmaceutical active ingredients containing related brand and generic drugs:


Dilora available forms, composition, doses:


Dilora destination | category:


Dilora Anatomical Therapeutic Chemical codes:


Dilora pharmaceutical companies:


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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

Can i drive or operate heavy machine after consuming Dilora?

Depending on the reaction of the Dilora after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Dilora 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.

Is Dilora addictive or habit forming?

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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Review

sdrugs.com conducted a study on Dilora, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Dilora consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

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


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