Desloratadine
Sun Pharmaceutical Industries Limited
HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use desloratadine safely and effectively. See full prescribing information for desloratadine tablets.Desloratadine Tablets for oral useInitial U.S. Approval: 2001 INDICATIONS AND USAGEDesloratadine tablets are 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) DOSAGE AND ADMINISTRATIONDosage (by age):Adults and adolescents 12 years of age and over: Desloratadine tablets - one 5 mg tablet once daily DOSAGE FORMS AND STRENGTHS Desloratadine tablets - 5 mg (3) CONTRAINDICATIONS Hypersensitivity (4, 6.2) WARNINGS AND PRECAUTIONS Hypersensitivity reactions including rash, pruritus, urticaria, edema, dyspnea, and anaphylaxis have been reported. In such cases, stop desloratadine at once and consider alternative treatments. (5.1) Side Effects 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 CARACO Pharmaceutical Laboratories Ltd. at 1-800-818-4555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.USE IN SPECIFIC POPULATIONS Renal impairment: dosage adjustment is recommended (2.5, 8.6, 12.3) Hepatic impairment: dosage adjustment is recommended (2.5, 8.7, 12.3)
FULL PRESCRIBING INFORMATION: CONTENTS*
- 1 DESLORATADINE INDICATIONS AND USAGE
- 2 DESLORATADINE DOSAGE AND ADMINISTRATION
- 3 DOSAGE FORMS AND STRENGTHS
- 4 DESLORATADINE CONTRAINDICATIONS
- 5 WARNINGS AND PRECAUTIONS
- 6 DESLORATADINE ADVERSE REACTIONS
- 7 DRUG INTERACTIONS
- 8 USE IN SPECIFIC POPULATIONS
- 9 DRUG ABUSE AND DEPENDENCE
- 10 OVERDOSAGE
- 11 DESLORATADINE DESCRIPTION
- 12 CLINICAL PHARMACOLOGY
- 13 NONCLINICAL TOXICOLOGY
- 14 CLINICAL STUDIES
- 16 HOW SUPPLIED/STORAGE AND HANDLING
- 17 PATIENT COUNSELING INFORMATION
- PRINCIPAL DISPAY PANEL - Label
FULL PRESCRIBING INFORMATION
1 INDICATIONS AND USAGE
1.1 Seasonal Allergic Rhinitis
1.2 Perennial Allergic Rhinitis
1.3 Chronic Idiopathic Urticaria
2 DOSAGE AND ADMINISTRATION
2.1 Adults and adolescents 12 years of age and over
2.5 Adults with Hepatic or Renal Impairment
[see Clinical Pharmacology (12.3)].
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
[see Warnings and Precautions (5.1) and Adverse Reactions (6.2)].
5 WARNINGS AND PRECAUTIONS
5.1 Hypersensitivity Reactions
[See Adverse Reactions (6.2).]
6 ADVERSE REACTIONS
- Hypersensitivity reactions. [See Warnings and Precautions (5.1).]
6.1 Clinical Trials Experience
Adults and Adolescents
Allergic Rhinitis:Table 1
Adverse Event
|
Desloratadine
Tablets
5 mg (n=1,655) |
Placebo (n=1,652) |
Infections and Infestations
|
||
Pharyngitis |
4.1% |
2% |
Nervous System Disorders
|
||
Somnolence |
2.1% |
1.8% |
Gastrointestinal Disorders
|
||
Dry Mouth |
3% |
1.9% |
Musculoskeletal and Connective Tissue Disorders
|
||
Myalgia |
2.1% |
1.8% |
Reproductive System and Breast Disorders
|
||
Dysmenorrhea |
2.1% |
1.6% |
General Disorders and Administration Site Conditions
|
||
Fatigue |
2.1% |
1.2% |
The frequency and magnitude of laboratory and electrocardiographic abnormalities were similar in desloratadine and placebo-treated patients.
Chronic Idiopathic Urticaria:
6.2 Postmarketing Experience
7 DRUG INTERACTIONS
7.1 Inhibitors of Cytochrome P450 3A4
[See Clinical Pharmacology (12.3).]
7.2 Fluoxetine
[See Clinical Pharmacology (12.3).]
7.3 Cimetidine
[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, desloratadine should be used during pregnancy only if clearly needed.
[See Nonclinical Toxicology (13.2).]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.
8.4 Pediatric Use
8.5 Geriatric Use
[See Clinical Pharmacology (12.3).]
8.6 Renal Impairment
[see Dosage and Administration (2.5) and Clinical Pharmacology (12.3)].
8.7 Hepatic Impairment
[see Dosage and Administration (2.5) and Clinical Pharmacology (12.3)].
9 DRUG ABUSE AND DEPENDENCE
10 OVERDOSAGE
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 postmarketing 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)].
2211 DESCRIPTION
Desloratadine tablets are blue, circular, film-coated tablets containing 5 mg desloratadine, an antihistamine, to be administered orally. Desloratadine tablets also contain the following excipients: corn starch, microcrystalline cellulose, meglumine, pregelatinized starch, sodium starch glycolate and sodium stearyl fumarate, coating material consisting of hypromellose, titanium dioxide, polyethylene glycol, polysorbate 80 and FD&C Blue #2 Aluminum Lake.
19192Hb
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
11in vitro1
12.2 Pharmacodynamics
Wheal and Flare: Human histamine skin wheal studies following single and repeated 5 mg doses of desloratadine have shown that the drug exhibits an antihistaminic effect by 1 hour; this activity may persist for as long as 24 hours. There was no evidence of histamine-induced skin wheal tachyphylaxis within the desloratadine 5 mg group over the 28-day treatment period. The clinical relevance of histamine wheal skin testing is unknown.
Effects on QTc:desloratadine12.3 Pharmacokinetics
Absorption
Following oral administration of a desloratadine 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 desloratadine.
Distribution
Desloratadine and 3-hydroxydesloratadine are approximately 82% to 87% and 85% to 89% bound to plasma proteins, respectively. Protein binding of desloratadine and 3-hydroxydesloratadine was unaltered in subjects with impaired renal function.
Metabolism
Desloratadine (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 desloratadine. In pharmacokinetic studies (n=3,748), approximately 6% of subjects were poor metabolizers of desloratadine (defined as a subject with an AUC ratio of 3-hydroxydesloratadine to desloratadine less than 0.1, or a subject with a desloratadine 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 desloratadine in the poor metabolizers was approximately 6-fold greater than in the subjects who are not poor metabolizers. Subjects who are poor metabolizers of desloratadine cannot be prospectively identified and will be exposed to higher levels of desloratadine following dosing with the recommended dose of desloratadine. In multidose clinical safety studies, where metabolizer status was identified, a total of 94 poor metabolizers and 123 normal metabolizers were enrolled and treated with desloratadine oral solution for 15 to 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 desloratadine 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 desloratadine.
Special Populations
Geriatric Subjects: In older subjects (≥65 years old; n=17) following multiple-dose administration of desloratadine tablets, the mean Cmax and AUC values for desloratadine were 20% greater than in younger subjects (<65 years old). The oral total body clearance (CL/F) when normalized for body weight was similar between the two age groups. The mean plasma elimination half-life of desloratadine was 33.7 hr in subjects ≥65 years old. The pharmacokinetics for 3-hydroxydesloratadine appeared unchanged in older versus younger subjects. These age-related differences are unlikely to be clinically relevant and no dosage adjustment is recommended in elderly subjects.
Renally Impaired: Desloratadine pharmacokinetics following a single dose of 7.5 mg were characterized in patients with mild (n=7; creatinine clearance 51 to 69 mL/min/1.73 m2), moderate (n=6; creatinine clearance 34 to 43 mL/min/1.73 m2), and severe (n=6; creatinine clearance 5 to 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. Desloratadine and 3-hydroxydesloratadine were poorly removed by hemodialysis. Plasma protein binding of desloratadine and 3-hydroxydesloratadine was unaltered by renal impairment. Dosage adjustment for patients with renal impairment is recommended [see Dosage and Administration (2.5)].
Hepatically Impaired: Desloratadine pharmacokinetics were characterized following 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 desloratadine in patients with mild, moderate, and severe hepatic impairment was 37%, 36%, and 28% of that in normal subjects, respectively. An increase in the mean elimination half-life of desloratadine in patients with hepatic impairment was observed. For 3-hydroxydesloratadine, the mean 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 desloratadine tablets had 10% and 3% higher desloratadine 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:maxmax
Drug Interactions:max0-24 hrs
Desloratadine
|
3-Hydroxydesloratadine
|
|||
Cmax
|
AUC0–24 hrs
|
Cmax
|
AUC0–24 hrs
|
|
Erythromycin (500 mg Q8h) |
+ 24% |
+ 14% |
+ 43% |
+ 40% |
Ketoconazole (200 mg Q12h) |
+ 45% |
+ 39% |
+ 43% |
+ 72% |
Azithromycin (500 mg day 1, 250 mg QD x 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 desloratadine was assessed using a loratadine study in rats and a desloratadine study in mice. In a 2-year study in rats, loratadine was administered in the diet at doses up to 25 mg/kg/day (estimated desloratadine and desloratadine metabolite exposures were approximately 30 times the AUC in humans at the recommended daily oral dose). 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 desloratadine and desloratadine 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 desloratadine 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 desloratadine, respectively, did not show significant increases in the incidence of any tumors. The estimated desloratadine and desloratadine metabolite exposures in mice at these doses were 12 and 27 times, respectively, the AUC in humans at the recommended daily oral dose.
Genotoxicity Studies:
In genotoxicity studies with desloratadine, there was no evidence of genotoxic potential in 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:
13.2 Animal Toxicology and/or Pharmacology
Reproductive Toxicology Studies:
14 CLINICAL STUDIES
14.1 Seasonal Allergic Rhinitis
Table 3
Treatment Group (n) |
Mean Baseline (SEM) |
Change from Baseline (SEM) |
Placebo Comparison (P-value) |
---|---|---|---|
SEM=Standard Error of the Mean |
|||
Desloratadine
5 mg (171) |
14.2 (0.3) |
-4.3 (0.3) |
P<0.01 |
Placebo (173) |
13.7 (0.3) |
-2.5 (0.3) |
14.2 Perennial Allergic Rhinitis
Table 4
Treatment Group (n) |
Mean Baseline (SEM) |
Change from Baseline (SEM) |
Placebo Comparison (P-value) |
---|---|---|---|
SEM=Standard Error of the Mean |
|||
Desloratadine
5 mg (337) |
12.37 (0.18) |
-4.06 (0.21) |
P=0.01 |
Placebo (337) |
12.3 (0.18) |
-3.27 (0.21) |
14.3 Chronic Idiopathic Urticaria
Table 5
Treatment Group (n) |
Mean Baseline (SEM) |
Change from Baseline (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 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
Blue, circular, biconvex, film-coated tablets debossed with “5” on one side and plain on other side; that are packaged in high-density polyethylene plastic bottles:
Bottle of 30’s with child Resistant Cap ………………………… NDC 62756-523-83
Bottle of 100’s with child Resistant Cap ……………………….. NDC 62756-523-88
Bottle of 100’s with Non child Resistant Cap……………………NDC 62756-523-08
Bottle of 500’s with Non child Resistant Cap……………………NDC 62756-523-13
Bottle of 1000’s with Non child Resistant Cap ………………… NDC 62756-523-18
Storage:
17 PATIENT COUNSELING INFORMATION
[See FDA-Approved Patient Labeling.]
17.1 Information for Patients
- Patients should be instructed to use desloratadine tablets as directed.
- As there are no food effects on bioavailability, patients can be instructed that desloratadine tablets may be taken without regard to meals.
- Patients should be advised not to increase the dose or dosing frequency as studies have not demonstrated increased effectiveness at higher doses and somnolence may occur.
PATIENT INFORMATION
Desloratadine Tablets
What are desloratadine tablets?
Desloratadine tablets are prescription medicine that contains the medicine desloratadine (an antihistamine).
- 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.
Who should not take desloratadine tablets?
- are allergic to desloratadine or any of the ingredients in desloratadine tablets. See the end of this leaflet for a complete list of ingredients.
- are allergic to loratadine (Alavert*, Claritin*).
What should I tell my doctor before taking desloratadine tablets?
- have liver or kidney problems.
- have any other medical conditions.
- are pregnant or plan to become pregnant. It is not known if desloratadine tablets will harm your unborn baby. Talk to your doctor if you are pregnant or plan to become pregnant.
- are breast-feeding or plan to breast-feed. Desloratadine can pass into your breast milk. Talk to your doctor about the best way to feed your baby if you take desloratadine tablets.
- ketoconazole (Nizoral*)
- erythromycin (Ery-tab*, Eryc*, PCE*)
- azithromycin (Zithromax*, Zmax*)
- antihistamines
- fluoxetine (Prozac*)
- cimetidine (Tagamet*)
How should I take desloratadine tablets?
- Take desloratadine tablets exactly as your doctor tells you to take it.
- Do not change your dose of desloratadine tablets or take more often than prescribed.
- Desloratadine tablets can be taken with or without food.
- If you take too many desloratadine tablets, call your doctor or get medical attention right away.
- Allergic reactions. Stop taking desloratadine 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
- sore throat
- dry mouth
- muscle pain
- tiredness
- sleepiness
- menstrual pain
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store desloratadine tablets?
- Store desloratadine tablets at 25°C (77°F); excursions permitted to 15-30°C (59-86°F).
- Desloratadine tablets are sensitive to heat. Do not store above 86°F (30°C).
- Protect desloratadine tablets from moisture.
General information about desloratadine tablets
What are the ingredients in desloratadine tablets?
Active ingredient:
Inactive ingredients:
Caraco Pharmaceutical Laboratories, Ltd.
Sun Pharmaceutical Industries Ltd.
PRINCIPAL DISPAY PANEL - Label
NDC 62756-523-88
Desloratadine Tablets
5 mg
Rx only
100 TABLETS
SUN PHARMA
PHARMACIST: Please dispense with Patient Information Sheet provided separately to each patient.
DesloratadineDesloratadine TABLET, FILM COATED
|