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Levocetirizine

Class: Second Generation Antihistamines
ATC Class: R06AE09
VA Class: AH109
Chemical Name: [2-[4-[(R)-p-Chloro-α-phenylbenzyl]-1-piperazinyl]ethoxy]acetic acid
Molecular Formula: C21H25ClN2O3
CAS Number: 130018-77-8
Brands: Xyzal

Medically reviewed by Drugs.com on Jan 25, 2021. Written by ASHP.

Introduction

Second generation antihistamine; R-enantiomer of cetirizine.

Uses for Levocetirizine

Allergic Rhinitis

Symptomatic relief of seasonal (e.g., hay fever) and perennial (nonseasonal) allergic rhinitis.

Chronic Idiopathic Urticaria

Symptomatic treatment of uncomplicated skin manifestations of chronic idiopathic urticaria.

Levocetirizine Dosage and Administration

Administration

Oral Administration

Administer orally once daily in the evening without regard to meals.

Tablets are scored and can be broken in half (each half providing a dose of 2.5 mg).

Dosage

Available as levocetirizine dihydrochloride; dosage expressed in terms of the salt.

5-mg dose administered as oral solution containing 2.5 mg/5 mL is bioequivalent to 5-mg tablet.

Pediatric Patients

Allergic Rhinitis
Seasonal
Oral

Children 2–5 years of age: 1.25 mg once daily (as oral solution). (See Pediatric Use under Cautions.)

Children 6–11 years of age: 2.5 mg once daily.

Children ≥12 years of age: 5 mg once daily; alternatively, 2.5 mg once daily may be adequate for some patients.

Perennial
Oral

Children 6 months to 5 years of age: 1.25 mg once daily (as oral solution). (See Pediatric Use under Cautions.)

Children 6–11 years of age: 2.5 mg once daily.

Children ≥12 years of age: 5 mg once daily; alternatively, 2.5 mg once daily may be adequate for some patients.

Chronic Idiopathic Urticaria
Oral

Children 6 months to 5 years of age: 1.25 mg once daily (as oral solution). (See Pediatric Use under Cautions.)

Children 6–11 years of age: 2.5 mg once daily.

Children ≥12 years of age: 5 mg once daily; alternatively, 2.5 mg once daily may be adequate for some patients.

Adults

Allergic Rhinitis
Oral

5 mg once daily; alternatively, 2.5 mg once daily may be adequate for some patients.

Chronic Idiopathic Urticaria
Oral

5 mg once daily; alternatively, 2.5 mg once daily may be adequate for some patients.

Prescribing Limits

Pediatric Patients

Allergic Rhinitis
Seasonal
Oral

Children 2–5 years of age: Maximum 1.25 mg daily; higher dosages associated with increased risk of somnolence. (See Absorption: Special Populations, under Pharmacokinetics.)

Children 6–11 years of age: Maximum 2.5 mg daily; higher dosages associated with increased risk of somnolence.

Children ≥12 years of age: Maximum 5 mg daily; higher dosages associated with increased risk of somnolence.

Perennial
Oral

Children 6 months to 5 years of age: Maximum 1.25 mg daily; higher dosages associated with increased risk of somnolence. (See Absorption: Special Populations, under Pharmacokinetics.)

Children 6–11 years of age: Maximum 2.5 mg daily; higher dosages associated with increased risk of somnolence.

Children ≥12 years of age: Maximum 5 mg daily; higher dosages associated with increased risk of somnolence.

Chronic Idiopathic Urticaria
Oral

Children 6 months to 5 years of age: Maximum 1.25 mg daily; higher dosages associated with increased risk of somnolence. (See Absorption: Special Populations, under Pharmacokinetics.)

Children 6–11 years of age: Maximum 2.5 mg daily; higher dosages associated with increased risk of somnolence.

Children ≥12 years of age: Maximum 5 mg daily; higher dosages associated with increased risk of somnolence.

Adults

Allergic Rhinitis
Oral

Maximum 5 mg daily; higher dosages associated with increased risk of somnolence.

Chronic Idiopathic Urticaria
Oral

Maximum 5 mg daily; higher dosages associated with increased risk of somnolence.

Special Populations

Hepatic Impairment

No dosage adjustment required.

Renal Impairment

Children 6 months to 11 years of age: Use contraindicated. (See Contraindications under Cautions.)

Adults and children ≥12 years of age: Adjust dosage based on degree of renal impairment. (See Table 1.)

Table 1. Dosage for Symptomatic Treatment of Allergic Rhinitis and Chronic Idiopathic Urticaria in Adults and Children ≥12 Years of Age with Renal Impairment133

Clcr (mL/minute)

Dosage

50–80

2.5 mg once daily

30–50

2.5 mg every other day

10–30

2.5 mg twice weekly (administered every 3–4 days)

<10 (or undergoing hemodialysis)

Use contraindicated

Geriatric Patients

Select dosage with caution (usually starting at low end of dosage range) because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy. (See Geriatric Use under Cautions.)

Cautions for Levocetirizine

Contraindications

  • Known hypersensitivity (e.g., urticaria, anaphylaxis) to levocetirizine or any ingredient in the formulation, or to cetirizine.

  • Adults and children ≥12 years of age with end-stage renal disease (Clcr <10 mL/minute) or undergoing hemodialysis.

  • Pediatric patients 6 months to 11 years of age with renal impairment.

Warnings/Precautions

CNS Effects

Somnolence, fatigue, and asthenia reported. Avoid performing hazardous activities requiring complete mental alertness or physical coordination (e.g., operating machinery, driving a motor vehicle). (See Advice to Patients.)

Specific Populations

Pregnancy

Category B.

Lactation

Expected to distribute into milk (since cetirizine is distributed into milk). Use not recommended.

Pediatric Use

Safety not established in children <6 months of age.

Efficacy of 1.25-mg once daily dosage (in pediatric patients 6 months to 5 years of age years of age) and 2.5-mg daily dosage (in pediatric patients 6–11 years of age) for management of allergic rhinitis is based on extrapolation of demonstrated efficacy of 5-mg daily dosage in pediatric patients ≥12 years of age and on pharmacokinetic comparisons in adults and children.

Efficacy of 1.25-mg once daily dosage (in pediatric patients 6 months to 5 years of age years of age), 2.5-mg daily dosage (in pediatric patients 6–11 years of age), and 5-mg daily dosage (in pediatric patients ≥12 years of age) for management of chronic idiopathic urticaria is based on extrapolation of demonstrated efficacy in adults and/or on pharmacokinetic comparisons in adults and children.

Risk of overdosage and toxicity (including death) in children <2 years of age receiving OTC preparations containing antihistamines, cough suppressants, expectorants, and nasal decongestants alone or in combination for relief of symptoms of upper respiratory tract infection. Clinicians should ask caregivers about use of nonprescription cough and cold preparations to avoid overdosage.

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults. Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy. (See Geriatric Patients under Dosage and Administration.) Periodic monitoring of renal function may be useful.

Hepatic Impairment

Pharmacokinetics not evaluated, but clearance unlikely to be decreased. (See Elimination under Pharmacokinetics.) Dosage adjustment not necessary.

Renal Impairment

Decreased clearance, resulting in increased risk of adverse effects. Dosage adjustment necessary based on degree of renal impairment. (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Children 6–11 months of age (with 1.25-mg once daily dosage): Diarrhea, constipation.

Children 1–5 years of age (with 1.25-mg twice daily dosage): Pyrexia, diarrhea, vomiting, otitis media.

Children 6–12 years of age (with 5-mg daily dosage): Pyrexia, cough, somnolence, epistaxis.

Adults and children ≥12 years of age (with 2.5- or 5-mg daily dosage): Somnolence, nasopharyngitis, fatigue, dry mouth, pharyngitis.

Interactions for Levocetirizine

No formal drug interaction studies with levocetirizine to date; studies have been performed with racemic cetirizine. (See Specific Drugs under Interactions.)

Does not inhibit CYP isoenzymes 1A2, 2C9, 2C19, 2A1, 2D6, 2E1, or 3A4. Does not induce UGT1A or CYP isoenzymes 1A2, 2C9, or 3A4. Unlikely to produce or be subject to pharmacokinetic interactions associated with metabolic enzyme systems.

Specific Drugs

Drug

Interaction

Comments

Azithromycin

No clinically important changes in ECG parameters observed following concomitant use with cetirizine, and no clinically important interactions reported following such concomitant use

Cimetidine

No pharmacokinetic interactions observed with cetirizine

CNS depressants (e.g., alcohol)

Possible additive CNS effects

Avoid concomitant use

Erythromycin

No clinically important changes in ECG parameters observed following concomitant use with cetirizine, and no clinically important interactions reported following such concomitant use

Ketoconazole

Prolongation of QTc interval (with an increase of 17.4 msec) observed following concomitant administration with cetirizine; no other clinically important interactions reported following such concomitant use

Not considered clinically important

Pseudoephedrine

No pharmacokinetic interactions observed with cetirizine

Ritonavir

Increased plasma AUC (42%), increased half-life (53%), and decreased clearance (29%) of cetirizine; disposition of ritonavir not altered following concomitant administration with cetirizine

Theophylline

Decreased clearance (16%) of cetirizine; disposition of theophylline not altered following concomitant administration with cetirizine

Levocetirizine Pharmacokinetics

Absorption

Bioavailability

Rapidly and extensively absorbed following oral administration, with peak plasma concentration usually attained in 0.9 hour (tablets) or 0.5 hour (oral solution).

Onset

Antihistaminic effects occur within 1 hour. Symptomatic improvement observed as early as 1 day after initiation of therapy for allergic rhinitis or chronic idiopathic urticaria.

Duration

Antihistaminic effects persist for at least 24 hours.

Food

A high-fat meal reduces peak plasma concentration by about 36% and delays time to peak plasma concentration by about 1.25 hours, but does not affect AUC.

Special Populations

In patients with renal impairment, AUC is increased by 1.8-, 3.2-, or 4.3-fold in those with mild, moderate, or severe impairment, respectively; AUC is increased by 5.7-fold in those with end-stage renal disease.

In pediatric patients 6 months to 5 years of age, plasma concentrations following administration of 1.25 mg once daily are similar to those observed in adults receiving 5 mg once daily. In pediatric patients 6–11 years of age, peak plasma concentration and AUC following administration of 5-mg dose are approximately twice that in adults.

Distribution

Extent

Average apparent volume of distribution is 0.4 L/kg, which represents distribution in total body water.

Expected to distribute into milk.

Plasma Protein Binding

Approximately 91–92% (mainly albumin).

Elimination

Metabolism

Metabolized to a limited extent (<14% of dose) by aromatic oxidation, N-dealkylation, O-dealkylation, and taurine conjugation.

Elimination Route

Excreted in urine (85.4%) (via glomerular filtration and active tubular secretion) and in feces (12.9%).

<10% of dose removed by standard 4-hour hemodialysis procedure.

Half-life

Approximately 8–9 hours in adults.

Special Populations

In patients with renal impairment, half-life is increased by 1.4-, 2-, or 2.9-fold in those with mild, moderate, or severe impairment, respectively; half-life is increased by fourfold in those with end-stage renal disease. Total body clearance also progressively decreases based on severity of renal impairment. (See Renal Impairment under Dosage and Administration.)

In pediatric patients 6–11 years of age receiving a single 5-mg dose, total body clearance was 30% greater and elimination half-life 24% shorter than those observed in adults.

In geriatric patients receiving 30 mg once daily for 6 days, total body clearance was 33% lower than that observed in younger adults; however, levocetirizine disposition appears to be dependent on renal function rather than on age.

Stability

Storage

Oral

Tablets and Oral Solution

20–25ºC (may be exposed to 15–30ºC).

Actions

  • Exhibits selective antagonism of peripheral histamine H1-receptors.

  • At half the dosage of cetirizine, appears to be as potent as cetirizine in inhibiting histamine-induced sneezing, increased nasal airway resistance, and skin wheal and flare.

  • Has been shown to exhibit greater and more consistent inhibition of histamine-induced wheal and flare compared with other antihistamines (e.g., desloratadine, fexofenadine, loratadine). Clinical relevance of histamine wheal skin testing is unknown.

Advice to Patients

  • Importance of taking only as prescribed; do not exceed prescribed dosage because of increased risk of somnolence.

  • Risk of somnolence; avoid performing activities requiring complete mental alertness or physical coordination (e.g., operating machinery, driving a motor vehicle).

  • Avoid concomitant use with alcohol or other CNS depressants.

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Levocetirizine Dihydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Solution

2.5 mg/5 mL

Xyzal

UCB

Tablets, film-coated

5 mg

Xyzal (scored)

UCB

AHFS DI Essentials™. © Copyright 2021, Selected Revisions February 4, 2013. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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