LEVOCETIRIZINE DIHYDROCHLORIDE- levocetirizine dihydrochloride solution

United States - English - NLM (National Library of Medicine)

Buy It Now

Active ingredient:
LEVOCETIRIZINE DIHYDROCHLORIDE (UNII: SOD6A38AGA) (LEVOCETIRIZINE - UNII:6U5EA9RT2O)
Available from:
Lannett Company, Inc.
INN (International Name):
LEVOCETIRIZINE DIHYDROCHLORIDE
Composition:
LEVOCETIRIZINE DIHYDROCHLORIDE 0.5 mg in 1 mL
Administration route:
ORAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
Levocetirizine dihydrochloride oral solution is indicated for the relief of symptoms associated with perennial allergic rhinitis in children 6 months to 2 years of age. Levocetirizine dihydrochloride oral solution is indicated for the treatment of the uncomplicated skin manifestations of chronic idiopathic urticaria in adults and children 6 months of age and older. The use of levocetirizine dihydrochloride is contraindicated in: Patients with known hypersensitivity to levocetirizine or any of the ingredients of levocetirizine dihydrochloride, or to cetirizine. Observed reactions range from urticaria to anaphylaxis [see Adverse Reactions (6.2)] . Patients with end-stage renal disease (CLCR < 10 mL/min) and patients undergoing hemodialysis Children 6 months to 11 years of age with impaired renal function Risk Summary Available data from published literature and postmarketing experience with levocetirizine use in pregnant women are insufficient to identify any drug-associated risks of miscarriage, birth defects
Product summary:
Levocetirizine Dihydrochloride Oral Solution is a clear, colorless liquid containing 0.5 mg of levocetirizine dihydrochloride per mL. Oral Solution available in 5 fl oz (148 mL) plastic bottle (0527-1917-69). Storage: Store at 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature].
Authorization status:
Abbreviated New Drug Application
Authorization number:
0527-1917-69

LEVOCETIRIZINE DIHYDROCHLORIDE- levocetirizine dihydrochloride solution

Lannett Company, Inc.

----------

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use LEVOCETIRIZINE DIHYDROCHLORIDE

ORAL SOLUTION safely and effectively. See full prescribing information for LEVOCETIRIZINE

DIHYDROCHLORIDE ORAL SOLUTION.

LEVOCETIRIZINE DIHYDROCHLORIDE oral solution

Initial U.S. Approval: 1995

INDICATIONS AND USAGE

Levocetirizine dihydrochloride oral solution, 2.5 mg/5 mL (0.5 mg/mL) is a histamine H -receptor antagonist indicated for:

The relief of symptoms associated with perennial allergic rhinitis (1.1)

The treatment of the uncomplicated skin manifestations of chronic idiopathic urticaria (1.2)

DOSAGE AND ADMINISTRATION

Perennial Allergic Rhinitis (2.1)

Children 6 months to 2 years of age: 1.25 mg (1/2 teaspoon oral solution) (2.5 mL) once daily in the evening

Chronic Idiopathic Urticaria (2.2)

Adults and children 12 years of age and older: 5 mg once daily in the evening

Children 6 to 11 years of age: 2.5 mg once daily in the evening

Children 6 months to 5 years of age: 1.25 mg (1/2 teaspoon oral solution) (2.5 mL) once daily in the evening

Renal Impairment

Adjust the dose in patients 12 years of age and older with decreased renal function (12.3)

DOSAGE FORMS AND STRENGTHS

Immediate release oral solution, 2.5 mg per 5 mL (0.5 mg per mL) (3)

CONTRAINDICATIONS

Patients with a known hypersensitivity to levocetirizine or any of the ingredients of levocetirizine dihydrochloride oral

solution or to cetirizine (4.1)

Patients with end-stage renal disease at less than 10 mL/min creatinine clearance or patients undergoing hemodialysis

(4.2)

Children 6 months to 11 years of age with renal impairment (4.3)

WARNINGS AND PRECAUTIONS

Avoid engaging in hazardous occupations requiring complete mental alertness such as driving or operating machinery

when taking levocetirizine dihydrochloride. (5.1)

Avoid concurrent use of alcohol or other central nervous system depressants with levocetirizine dihydrochloride. (5.1)

Use with caution in patients with predisposing factors of urinary retention (e.g. spinal cord lesion, prostatic hyperplasia).

Discontinue levocetirizine dihydrochloride if urinary retention occurs. (5.2)

ADVERSE REACTIONS

The most common adverse reactions (rate ≥2% and > placebo) were somnolence, nasopharyngitis, fatigue, dry mouth, and

pharyngitis in subjects 12 years of age and older, and pyrexia, somnolence, cough, and epistaxis in children 6 to 12 years of

age. In subjects 1 to 5 years of age, the most common adverse reactions (rate ≥2% and > placebo) were pyrexia, diarrhea,

vomiting, and otitis media. In subjects 6 to 11 months of age, the most common adverse reactions (rate ≥3% and >

placebo) were diarrhea and constipation. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Lannett Company, Inc. at 1-844-834-0530 or FDA at 1-

800-FDA-1088 or www.fda.gov/medwatch.

USE IN SPECIFIC POPULATIONS

Renal Impairment

Because levocetirizine dihydrochloride is substantially excreted by the kidneys, the risk of adverse reactions to this

drug may be greater in patients with impaired renal function. (8.6, 12.3)

Pediatric Use

Do not exceed the recommended doses of 2.5 mg and 1.25 mg once daily in children 6 to 11 years and 6 months to 5

years of age, respectively. Systemic exposure with these doses in respective pediatric age groups is comparable to that

from a 5 mg once daily dose in adults. (12.3)

See 17 for PATIENT COUNSELING INFORMATION.

Revised: 2/2019

FULL PRESCRIBING INFORMATION: CONTENTS*

1 INDICATIONS AND USAGE

1.1 Perennial Allergic Rhinitis

1.2 Chronic Idiopathic Urticaria

2 DOSAGE AND ADMINISTRATION

2.1 Perennial Allergic Rhinitis

2.2 Chronic Idiopathic Urticaria

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

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

8.2 Lactation

8.4 Pediatric Use

8.5 Geriatric Use

8.6 Renal Impairment

8.7 Hepatic Impairment

10 OVERDOSAGE

11 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

14 CLINICAL STUDIES

14.1 Perennial Allergic Rhinitis

14.2 Chronic Idiopathic Urticaria

16 HOW SUPPLIED/STORAGE AND HANDLING

17 PATIENT COUNSELING INFORMATION

Sections or subsections omitted from the full prescribing information are not listed.

FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

1.1 Perennial Allergic Rhinitis

Levocetirizine dihydrochloride oral solution is indicated for the relief of symptoms associated with

perennial allergic rhinitis in children 6 months to 2 years of age.

1.2 Chronic Idiopathic Urticaria

Levocetirizine dihydrochloride oral solution is indicated for the treatment of the uncomplicated skin

manifestations of chronic idiopathic urticaria in adults and children 6 months of age and older.

2 DOSAGE AND ADMINISTRATION

Levocetirizine dihydrochloride is available as 2.5 mg/5 mL (0.5 mg/mL) oral solution. Levocetirizine

dihydrochloride can be taken without regard to food consumption.

2.1 Perennial Allergic Rhinitis

Children 6 months to 2 Years of Age

The recommended initial dose of levocetirizine dihydrochloride is 1.25 mg (1/2 teaspoon oral solution)

(2.5 mL) once daily in the evening. The 1.25 mg once daily dose should not be exceeded based on

comparable exposure to adults receiving 5 mg [see Clinical Pharmacology (12.3)].

2.2 Chronic Idiopathic Urticaria

Adults and Children 12 Years of Age and Older

The recommended dose of levocetirizine dihydrochloride is 5 mg (2 teaspoons [10 mL] oral solution)

once daily in the evening. Some patients may be adequately controlled by 2.5 mg (1 teaspoon [5 mL] oral

solution) once daily in the evening.

Children 6 to 11 Years of Age

The recommended dose of levocetirizine dihydrochloride is 2.5 mg (1 teaspoon [5 mL] oral solution)

once daily in the evening. The 2.5 mg dose should not be exceeded because the systemic exposure with

5 mg is approximately twice that of adults [see Clinical Pharmacology (12.3)].

Children 6 months to 5 Years of Age

The recommended initial dose of levocetirizine dihydrochloride is 1.25 mg (1/2 teaspoon oral solution)

(2.5 mL) once daily in the evening. The 1.25 mg once daily dose should not be exceeded based on

comparable exposure to adults receiving 5 mg [see Clinical Pharmacology (12.3)].

Dose Adjustment for Renal and Hepatic Impairment

In adults and children 12 years of age and older with:

Mild renal impairment (creatinine clearance [CL

] = 50-80 mL/min): a dose of 2.5 mg once daily is

recommended;

Moderate renal impairment (CL

= 30-50 mL/min): a dose of 2.5 mg once every other day is

recommended;

Severe renal impairment (CL

= 10-30 mL/min): a dose of 2.5 mg twice weekly (administered once

every 3-4 days) is recommended;

End-stage renal disease patients (CL

< 10 mL/min) and patients undergoing hemodialysis should

not receive levocetirizine dihydrochloride oral solution.

No dose adjustment is needed in patients with solely hepatic impairment. In patients with both hepatic

impairment and renal impairment, adjustment of the dose is recommended.

3 DOSAGE FORMS AND STRENGTHS

Levocetirizine Dihydrochloride Oral Solution is a clear, colorless liquid containing 0.5 mg of

levocetirizine dihydrochloride per mL.

4 CONTRAINDICATIONS

The use of levocetirizine dihydrochloride is contraindicated in:

4.1 Patients with Known Hypersensitivity

Patients with known hypersensitivity to levocetirizine or any of the ingredients of levocetirizine

dihydrochloride, or to cetirizine. Observed reactions range from urticaria to anaphylaxis [see Adverse

Reactions (6.2)].

4.2 Patients with End-Stage Renal Disease

Patients with end-stage renal disease (CL

< 10 mL/min) and patients undergoing hemodialysis

4.3 Pediatric Patients with Impaired Renal Function

Children 6 months to 11 years of age with impaired renal function

5 WARNINGS AND PRECAUTIONS

5.1 Somnolence

In clinical trials the occurrence of somnolence, fatigue, and asthenia has been reported in some patients

under therapy with levocetirizine dihydrochloride. Patients should be cautioned against engaging in

hazardous occupations requiring complete mental alertness, and motor coordination such as operating

machinery or driving a motor vehicle after ingestion of levocetirizine dihydrochloride. Concurrent use

of levocetirizine dihydrochloride with alcohol or other central nervous system depressants should be

avoided because additional reductions in alertness and additional impairment of central nervous system

performance may occur.

5.2 Urinary Retention

Urinary retention has been reported post marketing with levocetirizine dihydrochloride. Levocetirizine

dihydrochloride should be used with caution in patients with predisposing factors of urinary retention

(e.g. spinal cord lesion, prostatic hyperplasia) as levocetirizine dihydrochloride may increase the risk

of urinary retention. Discontinue levocetirizine dihydrochloride if urinary retention occurs.

6 ADVERSE REACTIONS

Use of levocetirizine dihydrochloride has been associated with somnolence, fatigue, asthenia, and

urinary retention [see Warnings and Precautions (5)].

6.1 Clinical Trials Experience

The safety data described below reflect exposure to levocetirizine dihydrochloride in 2708 patients

with allergic rhinitis or chronic idiopathic urticaria in 14 controlled clinical trials of 1 week to 6

months duration.

months duration.

The short-term (exposure up to 6 weeks) safety data for adults and adolescents are based upon eight

clinical trials in which 1896 patients (825 males and 1071 females aged 12 years and older) were treated

with levocetirizine dihydrochloride 2.5, 5, or 10 mg once daily in the evening.

The short-term safety data from pediatric patients are based upon two clinical trials in which 243

children with allergic rhinitis (162 males and 81 females 6 to 12 years of age) were treated with

levocetirizine dihydrochloride 5 mg once daily for 4 to 6 weeks, one clinical trial in which 114

children (65 males and 49 females 1 to 5 years of age) with allergic rhinitis or chronic idiopathic

urticaria were treated with levocetirizine dihydrochloride 1.25 mg twice daily for 2 weeks, and one

clinical trial in which 45 children (28 males and 17 females 6 to 11 months of age) with symptoms of

allergic rhinitis or chronic urticaria were treated with levocetirizine dihydrochloride 1.25 mg once

daily for 2 weeks.

The long-term (exposure of 4 or 6 months) safety data in adults and adolescents are based upon two

clinical trials in which 428 patients (190 males and 238 females) with allergic rhinitis were exposed to

treatment with levocetirizine dihydrochloride 5 mg once daily. Long term safety data are also available

from an 18-month trial in 255 levocetirizine dihydrochloride-treated subjects 12-24 months of age.

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 trial of another drug

and may not reflect the rates observed in practice.

Adults and Adolescents 12 years of Age and Older

In studies up to 6 weeks in duration, the mean age of the adult and adolescent patients was 32 years, 44%

of the patients were men and 56% were women, and the large majority (more than 90%) was Caucasian.

In these trials 43% and 42% of the subjects in the levocetirizine dihydrochloride 2.5 mg and 5 mg

groups, respectively, had at least one adverse event compared to 43% in the placebo group.

In placebo-controlled trials of 1-6 weeks in duration, the most common adverse reactions were

somnolence, nasopharyngitis, fatigue, dry mouth, and pharyngitis, and most were mild to moderate in

intensity. Somnolence with levocetirizine dihydrochloride showed dose ordering between tested doses

of 2.5, 5 and 10 mg and was the most common adverse reaction leading to discontinuation (0.5%).

Table 1 lists adverse reactions that were reported in greater than or equal to 2% of subjects aged 12

years and older exposed to levocetirizine dihydrochloride 2.5 mg or 5 mg in eight placebo-controlled

clinical trials and that were more common with levocetirizine dihydrochloride than placebo.

Table 1: Adverse Reactions Reported in ≥ 2% of Subjects Aged 12 Years and Older Exposed to

Levocetirizine Dihydrochloride 2.5 mg or 5 mg Once Daily in Placebo-Controlled Clinical Trials

1-6 Weeks in Duration

Advers e

Reactions

Levocetirizine

Dihydrochloride

2.5 mg

(n = 421)

Levocetirizine

Dihydrochloride

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%)

Additional adverse reactions of medical significance observed at a higher incidence than in placebo in

adults and adolescents aged 12 years and older exposed to levocetirizine dihydrochloride are syncope

*

Rounded to the closest unit percentage

(0.2%) and weight increased (0.5%).

Pediatric Patients 6 to 12 Years of Age

A total of 243 pediatric patients 6 to 12 years of age received levocetirizine dihydrochloride 5 mg

once daily in two short-term placebo controlled double-blind trials. The mean age of the patients was

9.8 years, 79 (32%) were 6 to 8 years of age, and 50% were Caucasian. Table 2 lists adverse reactions

that were reported in greater than or equal to 2% of subjects aged 6 to 12 years exposed to

levocetirizine dihydrochloride 5 mg in placebo-controlled clinical trials and that were more common

with levocetirizine dihydrochloride than placebo.

Table 2: Adverse Reactions Reported in ≥ 2% of Subjects Aged 6-12 Years

Exposed to Levocetirizine Dihydrochloride 5 mg Once Daily in Placebo-Controlled

Clinical Trials 4 and 6 Weeks in Duration

Advers e

Reactions

Levocetirizine

Dihydrochloride 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%)

Pediatric Patients 1 to 5 Years of Age

A total of 114 pediatric patients 1 to 5 years of age received levocetirizine dihydrochloride 1.25 mg

twice daily in a two week placebo-controlled double-blind safety trial. The mean age of the patients

was 3.8 years, 32% were 1 to 2 years of age, 71% were Caucasian and 18% were Black. Table 3 lists

adverse reactions that were reported in greater than or equal to 2% of subjects aged 1 to 5 years

exposed to levocetirizine dihydrochloride 1.25 mg twice daily in the placebo-controlled safety trial and

that were more common with levocetirizine dihydrochloride than placebo.

Table 3: Adverse Reactions Reported in ≥ 2% of Subjects Aged 1-5 Years Exposed

to Levocetirizine Dihydrochloride 1.25 mg Twice Daily in a 2-Week Placebo-

Controlled Clinical Trial

Advers e

Reactions

Levocetirizine

Dihydrochloride 1.25 mg

Twice Daily

(n = 114)

Placebo

(n = 59)

Pyrexia

5 (4%)

1 (2%)

Diarrhea

4 (4%)

2 (3%)

Vomiting

4 (4%)

2 (3%)

Otitis Media

3 (3%)

0 (0%)

Pediatric Patients 6 to 11 Months of Age

A total of 45 pediatric patients 6 to 11 months of age received levocetirizine dihydrochloride 1.25 mg

once daily in a two week placebo-controlled double-blind safety trial. The mean age of the patients was

9 months, 51% were Caucasian and 31% were Black. Adverse reactions that were reported in more than

1 subject (i.e. greater than or equal to 3% of subjects) aged 6 to 11 months exposed to levocetirizine

dihydrochloride 1.25 mg once daily in the placebo-controlled safety trial and that were more common

*

Rounded to the closest unit percentage

*

Rounded to the closest unit percentage

with levocetirizine dihydrochloride than placebo included diarrhea and constipation which were

reported in 6 (13%) and 1 (4%) and 3 (7%) and 1 (4%) children in the levocetirizine dihydrochloride and

placebo-treated groups, respectively.

Long-Term Clinical Trials Experience

In two controlled clinical trials, 428 patients (190 males and 238 females) aged 12 years and older were

treated with levocetirizine dihydrochloride 5 mg once daily for 4 or 6 months. The patient

characteristics and the safety profile were similar to that seen in the short-term studies. Ten (2.3%)

patients treated with levocetirizine dihydrochloride discontinued because of somnolence, fatigue or

asthenia compared to 2 (<1%) in the placebo group.

There are no long term clinical trials in children below 12 years of age with allergic rhinitis or chronic

idiopathic urticaria.

Laboratory Test Abnormalities

Elevations of blood bilirubin and transaminases were reported in <1% of patients in the clinical trials.

The elevations were transient and did not lead to discontinuation in any patient.

6.2 Postmarketing Experience

In addition to the adverse reactions reported during clinical trials and listed above, the following

adverse reactions have also been identified during postapproval use of levocetirizine dihydrochloride.

Because these reactions 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.

Cardiac disorders: palpitations, tachycardia

Ear and labyrinth disorders: vertigo

Eye disorders: blurred vision, visual disturbances

Gastrointestinal disorders: nausea, vomiting

General disorders and administration site conditions: edema

Hepatobiliary disorders: hepatitis

Immune system disorders: anaphylaxis and hypersensitivity

Metabolism and nutrition disorders: increased appetite

Musculoskeletal, connective tissues, and bone disorders: arthralgia, myalgia

Nervous system disorders: dizziness, dysgeusia, febrile seizure, movement disorders (including

dystonia and oculogyric crisis), paraesthesia, seizure (reported in subjects with and without a known

seizure disorder), tremor

Psychiatric disorders: aggression and agitation, depression, hallucinations, insomnia, nightmare,

suicidal ideation

Renal and urinary disorders: dysuria, urinary retention

Respiratory, thoracic, and mediastinal disorders: dyspnea

Skin and subcutaneous tissue disorders: angioedema, fixed drug eruption, pruritus, rash and urticaria

Besides these reactions reported under treatment with levocetirizine dihydrochloride, other potentially

severe adverse events have been reported from the postmarketing experience with cetirizine. Since

levocetirizine is the principal pharmacologically active component of cetirizine, one should take into

account the fact that the following adverse events could also potentially occur under treatment with

levocetirizine dihydrochloride.

Cardiac disorders: severe hypotension

Gastrointestinal disorders: cholestasis

Nervous system disorders: extrapyramidal symptoms, myoclonus, orofacial dyskinesia, tic

Pregnancy, puerperium and perinatal conditions: stillbirth

Renal and urinary disorders: glomerulonephritis

Skin and subcutaneous tissue disorders: acute generalized exanthematous pustulosis (AGEP); rebound

pruritus - pruritus within a few days after discontinuation of cetirizine, usually after long-term use

(e.g. months to years) of cetirizine.

7 DRUG INTERACTIONS

In vitro data indicate that levocetirizine is unlikely to produce pharmacokinetic interactions through

inhibition or induction of liver drug-metabolizing enzymes. No in vivo drug-drug interaction studies

have been performed with levocetirizine. Drug interaction studies have been performed with racemic

cetirizine.

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

Ps eudoephedrine

Pharmacokinetic interaction studies performed with racemic cetirizine demonstrated that cetirizine did

not interact with antipyrine, pseudoephedrine, erythromycin, azithromycin, ketoconazole, and cimetidine.

There was a small decrease (~16%) in the clearance of cetirizine caused by a 400 mg dose of

theophylline. It is possible that higher theophylline doses could have a greater effect.

7.2 Ritonavir

Ritonavir increased the plasma AUC of cetirizine by about 42% accompanied by an increase in half-life

(53%) and a decrease in clearance (29%) of cetirizine. The disposition of ritonavir was not altered by

concomitant cetirizine administration.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

Available data from published literature and postmarketing experience with levocetirizine use in

pregnant women are insufficient to identify any drug-associated risks of miscarriage, birth defects, or

adverse maternal or fetal outcomes. In animal reproduction studies, there was no evidence of fetal harm

with administration of levocetirizine by the oral route to pregnant rats and rabbits, during the period of

organogenesis, at doses up to 390 times and 470 times, respectively, the maximum recommended human

dose (MRHD) in adults. In rats treated during late gestation and the lactation period, cetirizine had no

effects on pup development at oral doses up to approximately 60 times the MRHD in adults. In mice

treated during late gestation and the lactation period, cetirizine administered by the oral route to the

dams had no effects on pup development at a dose that was approximately 25 times the MRHD in adults;

however, lower pup weight gain during lactation was observed at a dose that was 95 times the MRHD

in adults (see Data).

The estimated background risk of major birth defects and miscarriage for the indicated population is

unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In

the U.S. general population, the estimated background risks of major birth defects and miscarriage in

clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data

Animal Data

In embryo-fetal development studies, pregnant rats received daily doses of levocetirizine up to 200

mg/kg/day from gestation days 6 to 15 and pregnant rabbits received daily doses of levocetirizine up to

120 mg/kg/day from gestation days 6 to 18. Levocetirizine produced no evidence of fetal harm in rats

and rabbits at doses up to 390 and 470 times the MRHD, respectively (on a mg/m basis with maternal

oral doses of 200 and 120 mg/kg/day in rats and rabbits, respectively).

No prenatal and postnatal development (PPND) studies in animals have been conducted with

levocetirizine. In a PPND study conducted in mice, cetirizine was administered at oral doses up to 96

mg/kg/day from gestation day 15 through lactation day 21. Cetirizine lowered pup body weight gain

during lactation at an oral dose in dams that was approximately 95 times the MRHD (on a mg/m basis

with a maternal oral dose of 96 mg/kg/day); however, there were no effects on pup weight gain at an

oral dose in dams that was approximately 25 times the MRHD (on a mg/m basis with a maternal oral

dose of 24 mg/kg/day). In a PPND study conducted in rats, cetirizine was administered at oral doses up

to 180 mg/kg/day from gestation day 17 to lactation day 22. Cetirizine did not have any adverse effects

on rat dams or offspring development at doses up to approximately 60 times the MRHD (on a mg/m

basis with a maternal oral dose of 30 mg/kg/day). Cetirizine caused excessive maternal toxicity at an

oral dose in dams that was approximately 350 times the MRHD (on a mg/m basis with a maternal oral

dose of 180 mg/kg/day).

8.2 Lactation

Risk Summary

There are no data on the presence of levocetirizine in human milk, the effects on the breastfed infant, or

the effects on milk production. However, cetirizine has been reported to be present in human breast

milk. In mice and beagle dogs, studies indicated that cetirizine was excreted in milk (see Data). When a

drug is present in animal milk, it is likely the drug will be present in human milk. The developmental and

health benefits of breastfeeding should be considered along with the mother’s clinical need for

levocetirizine dihydrochloride and any potential adverse effects on the breastfed child from

levocetirizine dihydrochloride or from the underlying maternal condition.

Data

Animal Data

Cetirizine was detected in the milk of mice. No adverse developmental effects on pups were seen when

cetirizine was administered orally to dams during lactation at a dose that was approximately 25 times the

MRHD in adults [see Use in Specific Populations (8.1)]. Studies in beagle dogs indicated that

approximately 3% of the dose of cetirizine was excreted in milk. The concentration of drug in animal

milk does not necessarily predict the concentration of drug in human milk.

8.4 Pediatric Use

The recommended dose of levocetirizine dihydrochloride for the treatment of the uncomplicated skin

manifestations of chronic idiopathic urticaria in patients 6 months to 17 years of age is based on

extrapolation of efficacy from adults 18 years of age and older [see Clinical Studies (14)].

The recommended dose of levocetirizine dihydrochloride in patients 6 months to 2 years of age for the

treatment of the symptoms of perennial allergic rhinitis and 6 months to 11 years of age with chronic

idiopathic urticaria is based on cross-study comparisons of the systemic exposure of levocetirizine

dihydrochloride in adults and pediatric patients and on the safety profile of levocetirizine

dihydrochloride in both adult and pediatric patients at doses equal to or higher than the recommended

dose for patients 6 months to 11 years of age.

The safety of levocetirizine dihydrochloride 5 mg once daily was evaluated in 243 pediatric patients 6

to 12 years of age in two placebo-controlled clinical trials lasting 4 and 6 weeks. The safety of

levocetirizine dihydrochloride 1.25 mg twice daily was evaluated in one 2-week clinical trial in 114

pediatric patients 1 to 5 years of age and the safety of levocetirizine dihydrochloride 1.25 mg once

daily was evaluated in one 2-week clinical trial in 45 pediatric patients 6 to 11 months of age [see

Adverse Reactions (6.1)].

The effectiveness of levocetirizine dihydrochloride 1.25 mg once daily (6 months to 5 years of age)

and 2.5 mg once daily (6 to 11 years of age) for the treatment of the symptoms of perennial allergic

rhinitis and chronic idiopathic urticaria is supported by the extrapolation of demonstrated efficacy of

levocetirizine dihydrochloride 5 mg once daily in patients 12 years of age and older based on the

pharmacokinetic comparison between adults and children.

Cross-study comparisons indicate that administration of a 5 mg dose of levocetirizine dihydrochloride

to 6 to 12 year old pediatric patients resulted in about 2-fold the systemic exposure (AUC) observed

when 5 mg of levocetirizine dihydrochloride was administered to healthy adults. Therefore, in children

6 to 11 years of age the recommended dose of 2.5 mg once daily should not be exceeded. In a

population pharmacokinetics study the administration of 1.25 mg once daily in children 6 months to 5

years of age resulted in systemic exposure comparable to 5 mg once daily in adults [see Dosage and

Administration (2.2), Clinical Studies (14), and Clinical Pharmacology (12.3)].

8.5 Geriatric Use

Clinical studies of levocetirizine dihydrochloride for each approved indication did not include

sufficient numbers of patients aged 65 years and older to determine whether they respond differently

than younger patients. Other reported clinical experience has not identified differences in responses

between the elderly and younger patients. In general, dose selection for an elderly patient should be

cautious, usually starting at the low end of the dosing range reflecting the greater frequency of

decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.

8.6 Renal Impairment

Levocetirizine dihydrochloride is known to be substantially excreted by the kidneys and the risk of

adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly

patients are more likely to have decreased renal function, care should be taken in dose selection and it

may be useful to monitor renal function [see Dosage and Administration (2) and Clinical Pharmacology

(12.3)].

8.7 Hepatic Impairment

As levocetirizine is mainly excreted unchanged by the kidneys, it is unlikely that the clearance of

levocetirizine is significantly decreased in patients with solely hepatic impairment [see Clinical

Pharmacology (12.3)].

10 OVERDOSAGE

Overdosage has been reported with levocetirizine dihydrochloride.

Symptoms of overdose may include drowsiness in adults. In children agitation and restlessness may

initially occur, followed by drowsiness. There is no known specific antidote to levocetirizine

dihydrochloride. Should overdose occur, symptomatic or supportive treatment is recommended.

Levocetirizine dihydrochloride is not effectively removed by dialysis, and dialysis will be ineffective

unless a dialyzable agent has been concomitantly ingested.

The acute maximal non-lethal oral dose of levocetirizine was 240 mg/kg in mice (approximately 190

times the maximum recommended daily oral dose in adults, approximately 230 times the maximum

recommended daily oral dose in children 6 to 11 years of age, and approximately 180 times the

maximum recommended daily oral dose in children 6 months to 5 years of age on a mg/m basis). In rats

the maximal non-lethal oral dose was 240 mg/kg (approximately 390 times the maximum recommended

daily oral dose in adults, approximately 460 times the maximum recommended daily oral dose in

children 6 to 11 years of age, and approximately 370 times the maximum recommended daily oral dose

in children 6 months to 5 years of age on a mg/m basis).

11 DESCRIPTION

Levocetirizine dihydrochloride, the active component of Levocetirizine Dihydrochloride Oral

Solution, is an orally active H -receptor antagonist. The chemical name is (R)-[2-[4-[(4-chlorophenyl)

phenylmethyl]-1-piperazinyl] ethoxy] acetic acid dihydrochloride. Levocetirizine dihydrochloride is

the R enantiomer of cetirizine hydrochloride, a racemic compound with antihistaminic properties. The

empirical formula of levocetirizine dihydrochloride is C

H ClN O ·2HCl. The molecular weight is

461.82 and the chemical structure is shown below:

Levocetirizine dihydrochloride is a white, crystalline powder and is water soluble.

Levocetirizine dihydrochloride 0.5 mg/mL oral solution is formulated as an immediate release, clear,

colorless liquid. Inactive ingredients are: sodium acetate trihydrate, glacial acetic acid, maltitol

solution, glycerin, methylparaben, propylparaben, sucralose, artificial grape flavor, purified water.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Levocetirizine, the active enantiomer of cetirizine, is an antihistamine; its principal effects are mediated

via selective inhibition of H receptors. The antihistaminic activity of levocetirizine has been

documented in a variety of animal and human models. In vitro binding studies revealed that levocetirizine

has an affinity for the human H -receptor 2-fold higher than that of cetirizine (Ki = 3 nmol/L vs. 6

nmol/L, respectively). The clinical relevance of this finding is unknown.

12.2 Pharmacodynamics

Studies in adult healthy subjects showed that levocetirizine at doses of 2.5 mg and 5 mg inhibited the

skin wheal and flare caused by the intradermal injection of histamine. In contrast, dextrocetirizine

exhibited no clear change in the inhibition of the wheal and flare reaction. Levocetirizine at a dose of 5

mg inhibited the wheal and flare caused by intradermal injection of histamine in 14 pediatric subjects

(aged 6 to 11 years) and the activity persisted for at least 24 hours. The clinical relevance of histamine

wheal skin testing is unknown.

A QT/QTc study using a single dose of 30 mg of levocetirizine did not demonstrate an effect on the

QTc interval. While a single dose of levocetirizine had no effect, the effects of levocetirizine may not

be at steady state following single dose. The effect of levocetirizine on the QTc interval following

multiple dose administration is unknown. Levocetirizine is not expected to have QT/QTc effects

because of the results of QTc studies with cetirizine and the long postmarketing history of cetirizine

without reports of QT prolongation.

12.3 Pharmacokinetics

Levocetirizine exhibited linear pharmacokinetics over the therapeutic dose range in adult healthy

subjects.

Absorption

Levocetirizine is rapidly and extensively absorbed following oral administration. In adults, peak plasma

concentrations are achieved 0.9 hour after administration of the oral tablet. The accumulation ratio

following daily oral administration is 1.12 with steady state achieved after 2 days. Peak concentrations

are typically 270 ng/mL and 308 ng/mL following a single and a repeated 5 mg once daily dose,

respectively. Food had no effect on the extent of exposure (AUC) of the levocetirizine tablet, but T

was delayed by about 1.25 hours and C

was decreased by about 36% after administration with a high

fat meal; therefore, levocetirizine can be administered with or without food.

A dose of 5 mg (10 mL) of levocetirizine dihydrochloride oral solution is bioequivalent to a 5 mg dose

of levocetirizine dihydrochloride tablets. Following oral administration of a 5 mg dose of

levocetirizine dihydrochloride oral solution to healthy adult subjects, the mean peak plasma

concentrations were achieved approximately 0.5 hour post dose.

Distribution

The mean plasma protein binding of levocetirizine in vitro ranged from 91 to 92%, independent of

concentration in the range of 90-5000 ng/mL, which includes the therapeutic plasma levels observed.

Following oral dosing, the average apparent volume of distribution is approximately 0.4 L/kg,

representative of distribution in total body water.

Metabolism

The extent of metabolism of levocetirizine in humans is less than 14% of the dose and therefore

differences resulting from genetic polymorphism or concomitant intake of hepatic drug metabolizing

enzyme inhibitors are expected to be negligible. Metabolic pathways include aromatic oxidation, N- and

O-dealkylation, and taurine conjugation. Dealkylation pathways are primarily mediated by CYP3A4

while aromatic oxidation involves multiple and/or unidentified CYP isoforms.

Elimination

The plasma half-life in adult healthy subjects was about 8 to 9 hours after administration of oral tablets

and oral solution, and the mean oral total body clearance for levocetirizine was approximately 0.63

mL/kg/min. The major route of excretion of levocetirizine and its metabolites is via urine, accounting

for a mean of 85.4% of the dose. Excretion via feces accounts for only 12.9% of the dose.

Levocetirizine is excreted both by glomerular filtration and active tubular secretion. Renal clearance of

levocetirizine correlates with that of creatinine clearance. In patients with renal impairment the

clearance of levocetirizine is reduced [see Dosage and Administration (2.2)].

Drug Interaction Studies

In vitro data on metabolite interaction indicate that levocetirizine is unlikely to produce, or be subject to

metabolic interactions. Levocetirizine at concentrations well above C

level achieved within the

therapeutic dose ranges is not an inhibitor of CYP isoenzymes 1A2, 2C9, 2C19, 2A1, 2D6, 2E1, and

3A4, and is not an inducer of UGT1A or CYP isoenzymes 1A2, 2C9 and 3A4.

No formal in vivo drug interaction studies have been performed with levocetirizine. Studies have been

performed with the racemic cetirizine [see Drug Interactions (7)].

Pediatric patients

Data from a pediatric pharmacokinetic study with oral administration of a single dose of 5 mg

levocetirizine in 14 children age 6 to 11 years with body weight ranging between 20 and 40 kg show

that C

and AUC values are about 2-fold greater than that reported in healthy adult subjects in a cross-

study comparison. The mean C

was 450 ng/mL, occurring at a mean time of 1.2 hours, weight-

normalized, total body clearance was 30% greater, and the elimination half-life 24% shorter in this

pediatric population than in adults.

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

age. A retrospective population pharmacokinetic analysis was conducted in 323 subjects (181 children 1

to 5 years of age, 18 children 6 to 11 years of age, and 124 adults 18 to 55 years of age) who received

single or multiple doses of levocetirizine ranging from 1.25 mg to 30 mg. Data generated from this

analysis indicated that administration of 1.25 mg once daily to children 6 months to 5 years of age

results in plasma concentrations similar to those of adults receiving 5 mg once daily.

Geriatric patients

Limited pharmacokinetic data are available in elderly subjects. Following once daily repeat oral

administration of 30 mg levocetirizine for 6 days in 9 elderly subjects (65-74 years of age), the total

body clearance was approximately 33% lower compared to that in younger adults. The disposition of

racemic cetirizine has been shown to be dependent on renal function rather than on age. This finding

would also be applicable for levocetirizine, as levocetirizine and cetirizine are both predominantly

excreted in urine. Therefore, the levocetirizine dihydrochloride dose should be adjusted in accordance

with renal function in elderly patients [see Dosage and Administration (2)].

Gender

Pharmacokinetic results for 77 patients (40 men, 37 women) were evaluated for potential effect of

gender. The half-life was slightly shorter in women (7.08 ± 1.72 hr) than in men (8.62 ± 1.84 hr);

however, the body weight-adjusted oral clearance in women (0.67 ± 0.16 mL/min/kg) appears to be

comparable to that in men (0.59 ± 0.12 mL/min/kg). The same daily doses and dosing intervals are

applicable for men and women with normal renal function.

Race

The effect of race on levocetirizine has not been studied. As levocetirizine is primarily renally

excreted, and there are no important racial differences in creatinine clearance, pharmacokinetic

characteristics of levocetirizine are not expected to be different across races. No race-related

differences in the kinetics of racemic cetirizine have been observed.

Renal impairment

Levocetirizine exposure (AUC) exhibited 1.8-, 3.2-, 4.3-, and 5.7-fold increase in mild, moderate,

severe, renal impaired, and end-stage renal disease patients, respectively, compared to healthy subjects.

The corresponding increases of half-life estimates were 1.4-, 2.0-, 2.9-, and 4-fold, respectively.

The total body clearance of levocetirizine after oral dosing was correlated to the creatinine clearance

and was progressively reduced based on severity of renal impairment. Therefore, it is recommended to

adjust the dose and dosing intervals of levocetirizine based on creatinine clearance in patients with mild,

moderate, or severe renal impairment. In end-stage renal disease patients (CL

< 10 mL/min)

levocetirizine is contraindicated. The amount of levocetirizine removed during a standard 4-hour

hemodialysis procedure was <10%.

The dosage of levocetirizine dihydrochloride should be reduced in patients with mild renal impairment.

Both the dosage and frequency of administration should be reduced in patients with moderate or severe

renal impairment [see Dosage and Administration (2.2)].

Hepatic impairment

Levocetirizine dihydrochloride has not been studied in patients with hepatic impairment. The non-renal

clearance (indicative of hepatic contribution) was found to constitute about 28% of the total body

clearance in healthy adult subjects after oral administration.

As levocetirizine is mainly excreted unchanged by the kidney, it is unlikely that the clearance of

levocetirizine is significantly decreased in patients with solely hepatic impairment [see Dosage and

Administration (2)].

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

No carcinogenicity studies have been performed with levocetirizine. However, evaluation of cetirizine

carcinogenicity studies is relevant for determination of the carcinogenic potential of levocetirizine. In a

2-year carcinogenicity study, in rats, cetirizine was not carcinogenic at dietary doses up to 20 mg/kg

(approximately 40, 40, 25, and 10 times the MRHDs in adults, children 6 to 11 years of age, children 2-

5 years, and children 6 months to 2 years of age, respectively, on a mg/m basis). In a 2-year

carcinogenicity study in mice, cetirizine caused an increased incidence of benign hepatic tumors in

males at a dietary dose of 16 mg/kg (approximately 15, 15, 9, and 5 times the MRHDs in adults, children

6 to 11 years of age, children 2-5 years, and children 6 months to 2 years of age, respectively, on a

mg/m basis). No increased incidence of benign tumors was observed at a dietary dose of 4 mg/kg

(approximately 4, 4, 2, and 1 times the MRHDs in adults, children 6 to 11 years of age, children 2-5

years, and children 6 months to 2 years of age, respectively on a mg/m basis). The clinical significance

of these findings during long-term use of levocetirizine dihydrochloride is not known.

Levocetirizine was not mutagenic in the Ames test, and not clastogenic in the human lymphocyte assay,

the mouse lymphoma assay, and in vivo micronucleus test in mice.

Fertility and reproductive performance were unaffected in male and female mice and rats that received

cetirizine at oral doses up to 64 and 200 mg/kg/day, respectively (approximately 60 and 390 times the

MRHD in adults on a mg/m basis).

14 CLINICAL STUDIES

14.1 Perennial Allergic Rhinitis

Adults and Adolescents 12 Years of Age and Older

The efficacy of levocetirizine dihydrochloride was evaluated in four randomized, placebo-controlled,

double-blind clinical trials in adult and adolescent patients 12 years and older with symptoms of

perennial allergic rhinitis. The four clinical trials include two dose-ranging trials of 4 weeks duration

and two efficacy trials (one 6-week and one 6-month) in patients with perennial allergic rhinitis.

These trials included a total of 1729 patients (752 males and 977 females) of whom 227 were

adolescents 12 to 17 years of age. Efficacy was assessed using a total symptom score from patient

recording of 4 symptoms (sneezing, rhinorrhea, nasal pruritus, and ocular pruritus) in three studies and 5

symptoms (sneezing, rhinorrhea, nasal pruritus, ocular pruritus, and nasal congestion) in one study.

Patients recorded symptoms using a 0-3 categorical severity scale (0 = absent, 1 = mild, 2 = moderate, 3

= severe) once daily in the evening reflective of the 24 hour treatment period. The primary endpoint

was the mean total symptom score averaged over the first week and over 4 weeks for perennial allergic

rhinitis trials.

The two dose-ranging trials were conducted to evaluate the efficacy of levocetirizine dihydrochloride

2.5, 5, and 10 mg once daily in the evening. These trials were 4 weeks in duration and included patients

with perennial allergic rhinitis. In these trials, each of the three doses of levocetirizine dihydrochloride

demonstrated greater decrease in the reflective total symptom score than placebo and the difference was

statistically significant for all three doses in the two studies. Results for one of these trials are shown

in Table 4.

Table 4: Mean Reflective Total Symptom Score in Allergic Rhinitis Dose-Ranging Trials

Treatment

N

Bas eline

On

Treatment

Adjus ted

Mean

Difference from Placebo

Es timate

95% CI

p-value

Perennial Allergic Rhinitis Trial – Reflective total symptom score

Levocetirizine

Dihydrochloride

7.14

4.12

1.17

(0.71, 1.63)

<0.001

*

2.5 mg

Levocetirizine

Dihydrochloride

5 mg

7.18

4.07

1.22

(0.76, 1.69)

<0.001

Levocetirizine

Dihydrochloride

10 mg

7.58

4.19

1.10

(0.64, 1.57)

<0.001

Placebo

7.22

5.29

One clinical trial evaluated the efficacy of levocetirizine dihydrochloride 5 mg once daily in the

evening compared to placebo in patients with perennial allergic rhinitis over a 6-week treatment period.

Another trial conducted over a 6-month treatment period assessed efficacy at 4 weeks. Levocetirizine

dihydrochloride 5 mg demonstrated a greater decrease from baseline in the reflective total symptom

score than placebo and the difference from placebo was statistically significant. Results of the former

are shown in Table 5.

Table 5: Mean Reflective Total Symptom Score in Allergic Rhinitis Trials

Treatment

N

Bas eline

On

Treatment

Adjus ted

Mean

Difference from Placebo

Es timate

95% CI

p-value

Perennial Allergic Rhinitis Trial – Reflective total symptom score

Levocetirizine

Dihydrochloride

5 mg

7.69

3.93

1.17

(0.70, 1.64)

<0.001

Placebo

7.44

5.10

Onset of action was evaluated in two environmental exposure unit studies in allergic rhinitis patients

with a single dose of levocetirizine dihydrochloride 2.5 or 5 mg. Levocetirizine dihydrochloride 5 mg

was found to have an onset of action 1 hour after oral intake. Onset of action was also assessed from the

daily recording of symptoms in the evening before dosing in the allergic rhinitis trials. In these trials,

onset of effect was seen after 1 day of dosing.

Pediatric Patients Less than 12 Years of Age

There are no clinical efficacy trials with levocetirizine dihydrochloride 2.5 mg once daily in pediatric

patients under 12 years of age, and no clinical efficacy trials with levocetirizine dihydrochloride 1.25

mg once daily in pediatric patients 6 months to 5 years of age. The clinical efficacy of levocetirizine

dihydrochloride in pediatric patients under 12 years of age has been extrapolated from adult clinical

efficacy trials based on pharmacokinetic comparisons [see Use in Specific Populations (8.4)].

14.2 Chronic Idiopathic Urticaria

Adult Patients 18 Years of Age and Older

The efficacy of levocetirizine dihydrochloride for the treatment of the uncomplicated skin

manifestations of chronic idiopathic urticaria was evaluated in two multi-center, randomized, placebo-

controlled, double-blind clinical trials of 4 weeks duration in adult patients 18 to 85 years of age with

chronic idiopathic urticaria. The two trials included one 4-week dose-ranging trial and one 4-week

single-dose level efficacy trial. These trials included 423 patients (139 males and 284 females). Most

Total symptom score is the sum of individual symptoms of sneezing, rhinorrhea, nasal pruritus, and ocular

pruritus as assessed by patients on a 0-3 categorical severity scale.

*

Total symptom score is the sum of individual symptoms of sneezing, rhinorrhea, nasal pruritus, and ocular pruritus

as assessed by patients on a 0-3 categorical severity scale.

patients (>90%) were Caucasian and the mean age was 41. Of these patients, 146 received

levocetirizine dihydrochloride 5 mg once daily in the evening. Efficacy was assessed based on patient

recording of pruritus severity on a severity score of 0-3 (0 = none to 3 = severe). The primary efficacy

endpoint was the mean reflective pruritus severity score over the first week and over the entire

treatment period. Additional efficacy variables were the instantaneous pruritus severity score, the

number and size of wheals, and duration of pruritus.

The dose-ranging trial was conducted to evaluate the efficacy of levocetirizine dihydrochloride 2.5, 5,

and 10 mg once daily in the evening. In this trial, each of the three doses of levocetirizine

dihydrochloride demonstrated greater decrease in the reflective pruritus severity score than placebo

and the difference was statistically significant for all three doses (see Table 6).

The single dose level trial evaluated the efficacy of levocetirizine dihydrochloride 5 mg once daily in

the evening compared to placebo in patients with chronic idiopathic urticaria over a 4-week treatment

period. Levocetirizine dihydrochloride 5 mg demonstrated a greater decrease from baseline in the

reflective pruritus severity score than placebo and the difference from placebo was statistically

significant.

Duration of pruritus, number and size of wheals, and instantaneous pruritus severity score also showed

significant improvement over placebo. The significant improvement in the instantaneous pruritus

severity score over placebo confirmed end of dosing interval efficacy (see Table 6).

Table 6: Mean Reflective Pruritus Severity Score in Chronic Idiopathic Urticaria Trials

Treatment

N

Bas eline

On

Treatment

Adjus ted

Mean

Difference from Placebo

Es timate

95% CI

p-value

Dose-Ranging Trial – Reflective pruritus severity score

Levocetirizine

Dihydrochloride

2.5 mg

2.08

1.02

0.82

(0.58, 1.06)

<0.001

Levocetirizine

Dihydrochloride

5 mg

2.07

0.92

0.91

(0.66, 1.16)

<0.001

Levocetirizine

Dihydrochloride

10 mg

2.04

0.73

1.11

(0.85, 1.37)

<0.001

Placebo

2.25

1.84

Chronic Idiopathic Urticaria Trial – Reflective pruritus severity score

Levocetirizine

Dihydrochloride

5 mg

2.07

0.94

0.62

(0.38, 0.86)

<0.001

Placebo

2.06

1.56

Pediatric Patients

There are no clinical efficacy trials in pediatric patients with chronic idiopathic urticaria [see Use in

Specific Populations (8.4)].

16 HOW SUPPLIED/STORAGE AND HANDLING

Levocetirizine Dihydrochloride Oral Solution is a clear, colorless liquid containing 0.5 mg of

levocetirizine dihydrochloride per mL.

Oral Solution available in 5 fl oz (148 mL) plastic bottle (0527-1917-69).

Storage:

Store at 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room

Temperature].

17 PATIENT COUNSELING INFORMATION

Somnolence

Caution patients against engaging in hazardous occupations requiring complete mental alertness, and

motor coordination such as operating machinery or driving a motor vehicle after ingestion of

levocetirizine dihydrochloride.

Concomitant Use of Alcohol and other Central Nervous System Depressants

Instruct patients to avoid concurrent use of levocetirizine dihydrochloride with alcohol or other central

nervous system depressants because additional reduction in mental alertness may occur.

Dosing of Levocetirizine Dihydrochloride

Do not exceed the recommended daily dose in adults and adolescents 12 years of age and older of 5 mg

once daily in the evening. In children 6 to 11 years of age the recommended dose is 2.5 mg once daily in

the evening. In children 6 months to 5 years of age, the recommended dose is 1.25 mg once daily in the

evening. Advise patients to not ingest more than the recommended dose of levocetirizine

dihydrochloride because of the increased risk of somnolence at higher doses.

The brands listed are the registered trademarks of their respective owners

Distributed by:

Lannett Company, Inc.

Philadelphia, PA 19136

10-1140

Rev. 02/2019

PRINCIPAL DISPLAY PANEL - 148 mL Bottle Label

NDC 0527-1917-69

Levocetirizine

Dihydrochloride

Oral Solution

2.5 mg/ 5 mL

(0.5 mg/ mL)

Rx Only

148 mL (5 fl oz)

Lannett

PRINCIPAL DISPLAY PANEL - 148 mL Carton Label

NDC 0527-1917-69

Levocetirizine

Dihydrochloride

Oral Solution

2.5 mg/ 5 mL

(0.5 mg/ mL)

Rx Only

148 mL (5 fl oz) Bottle

Lannett

LEVOCETIRIZINE DIHYDROCHLORIDE

levocetirizine dihydrochloride solution

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:0 527-19 17

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

LEVO CETIRIZINE DIHYDRO CHLO RIDE (UNII: SOD6 A38 AGA) (LEVOCETIRIZINE -

UNII:6 U5EA9 RT2O)

LEVOCETIRIZINE

DIHYDROCHLORIDE

0 .5 mg

in 1 mL

Inactive Ingredients

Ingredient Name

Stre ng th

SO DIUM ACETATE (UNII: 4550 K0 SC9 B)

ACETIC ACID (UNII: Q40 Q9 N0 6 3P)

GLYCERIN (UNII: PDC6 A3C0 OX)

PRO PYLPARABEN (UNII: Z8 IX2SC1OH)

METHYLPARABEN (UNII: A2I8 C7HI9 T)

SUCRALO SE (UNII: 9 6 K6 UQ3ZD4)

Lannett Company, Inc.

WATER (UNII: 0 59 QF0 KO0 R)

MALTITO L (UNII: D6 5DG142WK)

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:0 527-19 17-6 9

1 in 1 CARTON

0 5/15/20 17

1

148 mL in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA20 459 9

0 5/15/20 17

Labeler -

Lannett Company, Inc. (002277481)

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

Lannett Co mpany,

Inc .

16 16 30 0 33

ANALYSIS(0 527-19 17) , LABEL(0 527-19 17) , MANUFACTURE(0 527-19 17) , PACK(0 527-

19 17)

Revised: 2/2019

Similar products

Search alerts related to this product

Share this information