Levocetirizine Dihydrochloride

Sun Pharma Global FZE

HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use levocetirizine dihydrochloride tablets safely and effectively. See full prescribing information for levocetirizine dihydrochloride tablets. Levocetirizine Dihydrochloride Tablets, 5 mgInitial U.S. Approval: 1995 RECENT MAJOR CHANGES5.2INDICATIONS AND USAGE1 The treatment of the uncomplicated skin manifestations of chronic idiopathic urticaria (1.3) DOSAGE AND ADMINISTRATION Adults and children 12 years of age and older: 5 mg once daily in the evening (2.1) Children 6 to 11 years of age: 2.5 mg once daily in the evening (2.2) Renal Impairment Adjust the dose in patients 12 years of age and older with decreased renal function (2.4, 12.3) DOSAGE FORMS AND STRENGTHS Immediate-release breakable (scored) tablets, 5 mg (3) CONTRAINDICATIONS Patients with a known hypersensitivity to levocetirizine or any of the ingredients of levocetirizine dihydrochloride tablet or to cetirizine (4) Patients with end-stage renal disease at less than 10 mL/min creatinine clearance or patients undergoing hemodialysis (4) Children 6 months to 11 years of age with renal impairment (4) WARNINGS AND PRECAUTIONS Avoid engaging in hazardous occupations requiring complete mental alertness such as driving or operating machinery when taking levocetirizine dihydrochloride tablets (5.1). Avoid concurrent use of alcohol or other central nervous system depressants with levocetirizine dihydrochloride tablets (5.1). Use with caution in patients with predisposing factors of urinary retention (e.g. spinal cord lesion, prostatic hyperplasia). Discontinue levocetirizine dihydrochloride tablets if urinary retention occurs (5.2). Side Effects6.1To 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 POPULATIONS8.612.312.3Pediatric use information in pediatric patients (age 6 months to 5 years) is approved for UCB Inc.’s levocetirizine dihydrochloride drug product labeling. However, due to UCB Inc.’s marketing exclusivity rights; this drug product is not labeled for such use in those pediatric patients

FULL PRESCRIBING INFORMATION: CONTENTS*

• 1 LEVOCETIRIZINE DIHYDROCHLORIDE INDICATIONS AND USAGE
  • 1.3 Chronic Idiopathic Urticaria
• 2 LEVOCETIRIZINE DIHYDROCHLORIDE DOSAGE AND ADMINISTRATION
  • 2.1 Adults and Children 12 Years of Age and Older
  • 2.2 Children 6 to 11 Years of Age
  • 2.3 Children 6 months to 5 Years of Age
  • 2.4 Dose Adjustment for Renal and Hepatic Impairment
• 3 DOSAGE FORMS AND STRENGTHS
• 4 LEVOCETIRIZINE DIHYDROCHLORIDE CONTRAINDICATIONS
  • 4.1 Patients with known hypersensitivity
  • 4.2 Patients with end-stage renal disease
  • 4.3 Pediatric patients with impaired renal function
• 5 WARNINGS AND PRECAUTIONS
  • 5.1 Somnolence
  • 5.2 Urinary Retention
• 6 LEVOCETIRIZINE DIHYDROCHLORIDE ADVERSE REACTIONS
  • 6.1 Clinical Trials Experience
  • 6.2 Postmarketing Experience
• 7 DRUG INTERACTIONS
  • 7.1 Antipyrine, Azithromycin, Cimetidine, Erythromycin, Ketoconazole, Theophylline, and Pseudoephedrine
  • 7.2 Ritonavir
• 8 USE IN SPECIFIC POPULATIONS
  • 8.1 Pregnancy
  • 8.3 Nursing Mothers
  • 8.4 Pediatric Use
  • 8.5 Geriatric Use
  • 8.6 Renal Impairment
  • 8.7 Hepatic Impairment
• 10 OVERDOSAGE
• 11 LEVOCETIRIZINE DIHYDROCHLORIDE DESCRIPTION
• 12 CLINICAL PHARMACOLOGY
  • 12.1 Mechanism of Action
  • 12.2 Pharmacodynamics
  • 12.3 Pharmacokinetics
• 13 NONCLINICAL TOXICOLOGY
  • 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
  • 13.2 Animal Toxicology
• 14 CLINICAL STUDIES
  • 14.2 Chronic Idiopathic Urticaria
• 16 HOW SUPPLIED/STORAGE AND HANDLING
• 17 PATIENT COUNSELING INFORMATION
  • 17.1 Somnolence
  • 17.2 Concomitant Use of Alcohol and other Central Nervous System Depressants
  • 17.3 Dosing of Levocetirizine Dihydrochloride Tablets
• PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - LABEL

FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

1.3 Chronic Idiopathic Urticaria

2 DOSAGE AND ADMINISTRATION

2.1 Adults and Children 12 Years of Age and Older

2.2 Children 6 to 11 Years of Age

2.3 Children 6 months to 5 Years of Age

2.4 Dose Adjustment for Renal and Hepatic Impairment

• Mild renal impairment (creatinine clearance [CL_CR] = 50 to 80 mL/min): a dose of 2.5 mg once daily is recommended;
• Moderate renal impairment (CL_CR = 30 to 50 mL/min): a dose of 2.5 mg once every other day is recommended;
• Severe renal impairment (CL_CR = 10 to 30 mL/min): a dose of 2.5 mg twice weekly (administered once every 3 to 4 days) is recommended;
• End-stage renal disease patients (CL_CR < 10 mL/min) and patients undergoing hemodialysis should not receive levocetirizine dihydrochloride tablets.

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

4.1 Patients with known hypersensitivity

4.2 Patients with end-stage renal disease

4.3 Pediatric patients with impaired renal function

5 WARNINGS AND PRECAUTIONS

5.1 Somnolence

5.2 Urinary Retention

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

Adults and Adolescents 12 years of Age and Older

Table 1 Adverse Reactions Reported in ≥ 2%Rounded to the closest unit percentage of Subjects Aged 12 Years and Older Exposed to Levocetirizine 2.5 mg or 5 mg Once Daily in Placebo-Controlled Clinical Trials 1 to 6 Weeks in Duration

Adverse Reactions	Levocetirizine 2.5 mg (n = 421)	Levocetirizine 5 mg (n = 1070)	Placebo (n = 912)
Somnolence	22 (5%)	61 (6%)	16 (2%)
Nasopharyngitis	25 (6%)	40 (4%)	28 (3%)
Fatigue	5 (1%)	46 (4%)	20 (2%)
Dry Mouth	12 (3%)	26 (2%)	11 (1%)
Pharyngitis	10 (2%)	12 (1%)	9 (1%)

Pediatric Patients 6 to 12 Years of Age

Table 2 Adverse Reactions Reported in ≥2%Rounded to the closest unit percentage of Subjects Aged 6 to 12 Years Exposed to Levocetirizine 5 mg Once Daily in Placebo-Controlled Clinical Trials 4 and 6 Weeks in Duration

Adverse Reactions	Levocetirizine 5 mg (n = 243)	Placebo (n = 240)
Pyrexia	10 (4%)	5 (2%)
Cough	8 (3%)	2 (<1%)
Somnolence	7 (3%)	1 (<1%)
Epistaxis	6 (2%)	1 (<1%)

Clinical trial information in pediatric patients (age 6 months to 5 years) is approved for UCB Inc.’s levocetirizine dihydrochloride drug product labeling. However, due to UCB Inc.’s marketing exclusivity rights; this drug product is not labeled for such use in those pediatric patients.

Long-Term Clinical Trials Experience





Laboratory Test Abnormalities

6.2 Postmarketing Experience

7 DRUG INTERACTIONS

In vitro in vivo

7.1 Antipyrine, Azithromycin, Cimetidine, Erythromycin, Ketoconazole, Theophylline, and Pseudoephedrine

7.2 Ritonavir

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category B



Teratogenic Effects:

²

8.3 Nursing Mothers

²

8.4 Pediatric Use

[see Clinical Studies (14)].



[see Adverse Reactions (6.1)].



[see Dosage and Administration (2.2); Clinical Studies (14); and Clinical Pharmacology (12.3)].

Pediatric use information in pediatric patients (age 6 months to 5 years) is approved for UCB Inc.’s levocetirizine dihydrochloride drug product labeling. However, due to UCB Inc.’s marketing exclusivity rights; this drug product is not labeled for such use in those pediatric patients.

8.5 Geriatric Use

8.6 Renal Impairment

Dosage and Administration (2) and Clinical Pharmacology (12.3)

8.7 Hepatic Impairment

[see Clinical Pharmacology (12.3)].

10 OVERDOSAGE

²²

11 DESCRIPTION

_1212523

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

₁In vitro₁vs.

12.2 Pharmacodynamics

12.3 Pharmacokinetics

•    Absorption

_maxmax


•    Distribution

in vitro

•    Metabolism


 
•    Elimination

Dosage and Administration2.3
 
•    Drug Interaction Studies

In vitro_max

in vivoDrug Interactions (7)

•    Pediatric Patients

_maxmax

Dedicated pharmacokinetic studies have not been conducted in pediatric patients younger than 6 years of age.

Pharmacokinetic information in pediatric patients (age 1 to 5 years) is approved for UCB Inc.’s levocetirizine dihydrochloride drug product labeling. However, due to UCB Inc.’s marketing exclusivity rights; this drug product is not labeled for such use in those pediatric patients.

•    Geriatric Patients

Dosage and Administration (2)

•    Gender



•    Race



•    Renal Impairment



_CR

Dosage and Administration (2.4)

•    Hepatic Impairment



Dosage and Administration (2)

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

^{2 22}

in vivo

²

13.2 Animal Toxicology

<sup>2

2</sup>

14 CLINICAL STUDIES

14.2 Chronic Idiopathic Urticaria

Adult Patients 18 Years of Age and Older

Table 3 Mean Reflective Pruritus Severity Score in Chronic Idiopathic Urticaria Trials

Treatment	N	Baseline	On Treatment Adjusted Mean	Difference from Placebo
				Estimate	95% CI	p-value
Dose-Ranging Trial – Reflective pruritus severity score
Levocetirizine 2.5 mg	69	2.08	1.02	0.82	(0.58, 1.06)	<0.001
Levocetirizine 5 mg	62	2.07	0.92	0.91	(0.66, 1.16)	<0.001
Levocetirizine 10 mg	55	2.04	0.73	1.11	(0.85, 1.37)	<0.001
Placebo	60	2.25	1.84
Chronic Idiopathic Urticaria Trial – Reflective pruritus severity score
Levocetirizine 5 mg	80	2.07	0.94	0.62	(0.38, 0.86)	<0.001
Placebo	82	2.06	1.56

Pediatric Patients

[see Use in Specific Populations (8.4)].

16 HOW SUPPLIED/STORAGE AND HANDLING

Storage:

17 PATIENT COUNSELING INFORMATION

17.1 Somnolence

17.2 Concomitant Use of Alcohol and other Central Nervous System Depressants

17.3 Dosing of Levocetirizine Dihydrochloride Tablets

Pediatric use information in pediatric patients (age 6 months to 5 years) is approved for UCB Inc.’s levocetirizine dihydrochloride drug product labeling. However, due to UCB Inc.’s marketing exclusivity rights; this drug product is not labeled for such use in those pediatric patients.

Caraco Pharmaceutical Laboratories, Ltd.



Sun Pharmaceutical Industries

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - LABEL

NDC 47335-175-83
Levocetirizine Dihydrochloride Tablets
5 mg
For oral administration
Rx only
30 TABLETS
SUN PHARMA

Levocetirizine Dihydrochloride Levocetirizine Dihydrochloride TABLET, FILM COATED Product Information Product Type Human prescription drug label Item Code (Source) NDC:47335-175 Route of Administration ORAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength LEVOCETIRIZINE DIHYDROCHLORIDE LEVOCETIRIZINE 5 mg Inactive Ingredients Ingredient Name Strength ANHYDROUS LACTOSE cellulose, microcrystalline SILICON DIOXIDE MAGNESIUM STEARATE HYPROMELLOSES POLYETHYLENE GLYCOLS polysorbate 80 titanium dioxide Product Characteristics Color Size Imprint Code Shape WHITE 8 mm S OVAL Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:47335-175-83 30 in 1 BOTTLE 2 NDC:47335-175-88 100 in 1 BOTTLE 3 NDC:47335-175-08 100 in 1 BOTTLE 4 NDC:47335-175-18 1000 in 1 BOTTLE 5 NDC:47335-175-81 90 in 1 BOTTLE Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA090362 2013-02-05