desloratadine 5 MG Oral Tablet
Generic Name: DESLORATADINE
Brand Name: Desloratadine
- Substance Name(s):
- DESLORATADINE
DRUG INTERACTIONS
7 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 H 2 -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) .
]
OVERDOSAGE
10 In the event of overdose, consider standard measures to remove any unabsorbed drug.
Symptomatic and supportive treatment is recommended.
Desloratadine and 3-hydroxydesloratadine are not eliminated by hemodialysis.
Information regarding acute overdosage is limited to experience from post-marketing adverse event reports and from clinical trials conducted during the development of the Desloratadine product.
In 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 Desloratadine 45 mg for 10 days [ see Clinical Pharmacology (12.2) ].
Lethality occurred in rats at oral doses of 250 mg/kg or greater (estimated desloratadine and desloratadine 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 desloratadine exposures were approximately 290 times the human daily oral dose on a mg/m 2 basis).
No deaths occurred at oral doses up to 250 mg/kg in monkeys (estimated desloratadine exposures were approximately 810 times the human daily oral dose on a mg/m 2 basis).
DESCRIPTION
11 Desloratadine Tablets are light blue, round, tablets containing 5 mg desloratadine, an antihistamine, to be administered orally.
Desloratadine 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%.
Desloratadine 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: C 19 H 19 ClN 2 and a molecular weight of 310.8.
The chemical name is 8-chloro-6,11-dihydro-11-(4-piperdinylidene)-5 H -benzo[5,6]cyclohepta[1,2-b]pyridine and has the following structure: Chemical Structure
CLINICAL STUDIES
14 14.1 Seasonal Allergic Rhinitis The clinical efficacy and safety of Desloratadine Tablets were evaluated in over 2,300 patients 12 to 75 years of age with seasonal allergic rhinitis.
A total of 1,838 patients received 2.5 to 20 mg/day of Desloratadine in 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 Desloratadine 5 mg in the treatment of adult and adolescent patients with seasonal allergic rhinitis.
In a dose-ranging trial, Desloratadine 2.5 to 20 mg/day was studied.
Doses of 5, 7.5, 10, and 20 mg/day were superior to placebo; and no additional benefit was seen at doses above 5.0 mg.
In the same study, an increase in the incidence of somnolence was observed at doses of 10 mg/day and 20 mg/day (5.2% and 7.6%, respectively), compared to placebo (2.3%).
In two 4-week studies of 924 patients (aged 15 to 75 years) with seasonal allergic rhinitis and concomitant asthma, Desloratadine Tablets 5 mg once daily improved rhinitis symptoms, with no decrease in pulmonary function.
This supports the safety of administering Desloratadine Tablets to adult patients with seasonal allergic rhinitis with mild to moderate asthma.
Desloratadine Tablets 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 .
Table 3 TOTAL SYMPTOM SCORE (TSS) Changes in a 2 Week Clinical Trial in Patients with Seasonal Allergic Rhinitis Treatment Group (n) Mean Baseline At 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 Baseline Mean reduction in TSS averaged over the 2-week treatment period.
(SEM) Placebo Comparison ( P -value) SEM = Standard Error of the Mean Desloratadine 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 Desloratadine Tablets 5 mg across subgroups of patients defined by gender, age, or race.
14.2 Perennial Allergic Rhinitis The clinical efficacy and safety of Desloratadine 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 Desloratadine 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 Desloratadine Tablets 5 mg once daily was shown to significantly reduce the Total Symptom Score in patients with perennial allergic rhinitis (Table 4).
Table 4 TOTAL SYMPTOM SCORE (TSS) Changes in a 4 Week Clinical Trial in Patients with Perennial Allergic Rhinitis Treatment Group (n) Mean Baseline At 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 Baseline Mean reduction in TSS averaged over the 4 week treatment period.
(SEM) Placebo Comparison ( P -value) SEM = Standard Error of the Mean Desloratadine 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 Desloratadine Tablets 5 mg once daily was studied in 416 chronic idiopathic urticaria patients 12 to 84 years of age, of whom 211 received Desloratadine.
In two double-blind, placebo-controlled, randomized clinical trials of six weeks duration, at the pre-specified one-week primary time point evaluation, Desloratadine Tablets significantly reduced the severity of pruritus when compared to placebo (Table 5).
Secondary endpoints were also evaluated, and during the first week of therapy Desloratadine Tablets 5 mg reduced the secondary endpoints, “Number of Hives” and the “Size of the Largest Hive,” when compared to placebo.
Table 5 PRURITUS SYMPTOM SCORE Changes in the First Week of a Clinical Trial in Patients with Chronic Idiopathic Urticaria Treatment Group (n) Mean Baseline (SEM) Change from Baseline Mean 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=maximal symptom SEM = Standard Error of the Mean Desloratadine 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)
HOW SUPPLIED
16 /STORAGE AND HANDLING Desloratadine Tablets: Debossed “5”, light blue, round tablets that are packaged in high-density polyethylene plastic bottles of 30 (NDC 69543-107-30), 100 (NDC 69543-107-10), and 500 (NDC 69543-107-50).
Storage • Desloratadine Tablets: Store at 25° C (77° F); excursions permitted to 15° C – 30° C (59° F – 86° F) [see USP Controlled Room Temperature].
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.
GERIATRIC USE
8.5 Geriatric Use Clinical studies of desloratadine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.
Other reported clinical experience has not identified differences between the elderly and younger patients.
In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
[ See Clinical Pharmacology (12.3) .
]
DOSAGE FORMS AND STRENGTHS
3 Desloratadine Tablets are light blue round tablets debossed with “5” containing 5 mg desloratadine.
• Desloratadine Tablets – 5 mg ( 3 )
MECHANISM OF ACTION
12.1 Mechanism of Action Desloratadine is a long-acting tricyclic histamine antagonist with selective H 1 -receptor histamine antagonist activity.
Receptor binding data indicates that at a concentration of 2-3 ng/mL (7 nanomolar), desloratadine shows significant interaction with the human histamine H 1 -receptor.
Desloratadine inhibited histamine release from human mast cells in vitro .
Results of a radiolabeled tissue distribution study in rats and a radioligand H 1 -receptor binding study in guinea pigs showed that desloratadine did not readily cross the blood brain barrier.
The clinical significance of this finding is unknown.
INDICATIONS AND USAGE
1 Desloratadine Tablets are an H 1 – receptor antagonist indicated for: • Seasonal Allergic Rhinitis: relief of nasal and non-nasal symptoms in patients 12 years of age and older.
( 1.1 ) • 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 Desloratadine 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 Desloratadine 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 Desloratadine 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.
PEDIATRIC USE
8.4 Pediatric Use The recommended dose of Desloratadine Oral Solution in the pediatric population is based on cross-study comparison of the plasma concentration of Desloratadine in adults and pediatric subjects.
The safety of Desloratadine Oral Solution has been established in 246 pediatric subjects aged 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 Desloratadine are sufficiently similar in the pediatric and adult populations, it allows extrapolation from the adult efficacy data to pediatric patients.
The effectiveness of Desloratadine Oral Solution in these age groups is supported by evidence from adequate and well-controlled studies of Desloratadine Tablets in adults.
The safety and effectiveness of Desloratadine Tablets or Desloratadine Oral Solution have not been demonstrated in pediatric patients less than 6 months of age.
[ See Clinical Pharmacology (12.3) .
]
PREGNANCY
8.1 Pregnancy Pregnancy Category C: There are no adequate and well-controlled studies in pregnant women.
Because animal reproduction studies are not always predictive of human response, desloratadine should be used during pregnancy only if clearly needed.
Desloratadine was not teratogenic in rats or rabbits at approximately 210 and 230 times, respectively, the area under the concentration-time curve (AUC) in humans at the recommended daily oral dose.
An increase in pre-implantation loss and 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.
Desloratadine 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 desloratadine exposure in rabbits and the sum of desloratadine and its metabolites exposures in rats, respectively.
[ See Nonclinical Toxicology (13.2) .
]
NUSRING MOTHERS
8.3 Nursing Mothers Desloratadine passes into breast milk; therefore, a decision should be made whether to discontinue nursing or to discontinue desloratadine, taking into account the benefit of the drug to the nursing mother and the possible risk to the child.
WARNING AND CAUTIONS
5 WARNINGS AND PRECAUTIONS • Hypersensitivity reactions including rash, pruritus, urticaria, edema, dyspnea, and anaphylaxis have been reported.
In such cases, stop Desloratadine Tablets 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 Tablets should be stopped and alternative treatment should be considered.
[ See Adverse Reactions (6.2) .]
INFORMATION FOR PATIENTS
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information).
17.1 Information for Patients • Patients should be instructed to use Desloratadine Tablets as directed.
• As there are no food effects on bioavailability, patients can be instructed that Desloratadine Tablets may be taken without regard to meals.
• Patients should be advised not to increase the dose or dosing frequency as studies have not demonstrated increased effectiveness at higher doses and somnolence may occur.
DOSAGE AND ADMINISTRATION
2 Desloratadine Tablets may be taken without regard to meals.
Dosage (by age): Adults and Adolescents 12 Years of Age and Over: • Desloratadine Tablets – one 5 mg tablet once daily ( 2 ) 2.1 Adults and Adolescents 12 Years of Age and Over The recommended dose of Desloratadine 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) ].