Identification

Name
Levocetirizine
Accession Number
DB06282
Type
Small Molecule
Groups
Approved
Description

Levocetirizine is a third-generation non-sedative antihistamine indicated for the relief of symptoms associated with seasonal and perennial allergic rhinitis and uncomplicated skin manifestations of chronic idiopathic urticaria. It was developed from the second-generation antihistamine cetirizine. Levocetirizine is the R-enantiomer of the cetirizine racemate. Levocetirizine is an inverse agonist that decreases activity at histamine H1 receptors. This in turn prevents the release of other allergy chemicals and increased blood supply to the area, and provides relief from the typical symptoms of hay fever. It does not prevent the actual release of histamine from mast cells. Levocetirizine was approved by the United States Food and Drug Administration on May 25, 2007 and is marketed under the brand XYZAL® by sanofi-aventis U.S. LLC.

Structure
Thumb
Synonyms
  • 2-(2-{4-[(R)-(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethoxy)acetic acid
Product Ingredients
IngredientUNIICASInChI Key
Levocetirizine dihydrochlorideSOD6A38AGA130018-87-0PGLIUCLTXOYQMV-GHVWMZMZSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Levocetirizine DihydrochlorideTablet, film coated5 mg/1OralWinthrop U.S.2007-08-09Not applicableUs
Levocetirizine DihydrochlorideSolution0.5 mg/1mLOralWinthrop U.S.2008-04-02Not applicableUs
XyzalTablet5 mg/1OralPhysicians Total Care, Inc.2007-11-06Not applicableUs54868 582920180907 15195 ifaws8
XyzalSolution0.5 mg/1mLOralSanofi Aventis2017-07-24Not applicableUs
XyzalSolution0.5 mg/1mLOralUcb Inc2008-04-022018-06-08Us
XyzalTablet, film coated5 mg/1OralSanofi Aventis2007-08-09Not applicableUs00024 5800 90 nlmimage10 4112a085
XyzalTablet5 mg/1OralUCB Farchim S.A.2008-02-19Not applicableUs
XyzalTablet, film coated5 mg/1OralSanofi Aventis2017-07-24Not applicableUs
XyzalTablet, film coated5 mg/1OralUcb Inc2007-08-092019-01-19Us50474 0920 90 nlmimage10 0a47850c
XyzalSolution0.5 mg/1mLOralPhysicians Total Care, Inc.2010-04-27Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Levocetirizine DihydrochlorideTablet5 mg/1Oralbryant ranch prepack2014-10-27Not applicableUs
Levocetirizine DihydrochlorideSolution0.5 mg/1mLOralPerrigo New York Inc.2011-11-07Not applicableUs
Levocetirizine DihydrochlorideSolution0.5 mg/1mLOralLannett Company, Inc.2017-05-15Not applicableUs
Levocetirizine DihydrochlorideTablet, film coated5 mg/1OralDispensing Solutions, Inc.2011-09-06Not applicableUs
Levocetirizine DihydrochlorideSolution0.5 mg/1mLOralApotex Corporation2017-10-26Not applicableUs
Levocetirizine dihydrochlorideTablet, film coated5 mg/1OralSynthon Pharmaceuticals, Inc.2010-11-26Not applicableUs
Levocetirizine DihydrochlorideTablet5 mg/1OralVensun Pharmaceuticals, Inc.2014-10-27Not applicableUs
Levocetirizine DihydrochlorideTablet5 mg/1OralProficient Rx LP2015-02-13Not applicableUs
Levocetirizine DihydrochlorideTablet5 mg/1OralSciegen Pharmaceuticals Inc.2014-09-09Not applicableUs
Levocetirizine DihydrochlorideTablet5 mg/1OralYiling Pharmaceutical, Inc.2017-03-29Not applicableUs
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
24HR Allergy ReliefTablet, coated5 mg/1OralCardinal Health2018-03-12Not applicableUs
Allergy ReliefTablet, coated5 mg/1OralAlbertsons Companies2018-06-30Not applicableUs
Allergy ReliefTablet, coated5 mg/1OralAmerisource Bergen Drug Corportaion2018-04-20Not applicableUs
Childrens Xyzal AllergySolution0.5 mg/1mLOralChattem, Inc.2017-02-16Not applicableUs
Levocetirizine DihydrochlorideTablet, coated5 mg/1OralRugby2018-04-20Not applicableUs
Levocetirizine DihydrochlorideTablet, coated5 mg/1OralKroger Company2018-09-30Not applicableUs
Levocetirizine DihydrochlorideTablet, coated5 mg/1OralDr Reddy's Laboratories2018-03-12Not applicableUs
Levocetirizine DihydrochlorideTablet, coated5 mg/1OralWalgreens2018-03-12Not applicableUs
Levocetirizine DihydrochlorideTablet, coated5 mg/1OralCVS PHARMACY2018-04-15Not applicableUs
Levocetirizine DihydrochlorideTablet, coated5 mg/1OralWalgreens2018-03-26Not applicableUs
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
AlloPAXLevocetirizine dihydrochloride (3 g/3g) + Loratadine (3 g/3g)KitPharmaGenetico LLC2015-06-30Not applicableUs
Nazirex Compounding KitLevocetirizine dihydrochloride (1 g/1g) + Loratadine (1 g/1g)KitTopicalAlvix Laboratories2015-03-182015-07-01Us
International/Other Brands
Xusal
Categories
UNII
6U5EA9RT2O
CAS number
130018-77-8
Weight
Average: 388.89
Monoisotopic: 388.1553704
Chemical Formula
C21H25ClN2O3
InChI Key
ZKLPARSLTMPFCP-OAQYLSRUSA-N
InChI
InChI=1S/C21H25ClN2O3/c22-19-8-6-18(7-9-19)21(17-4-2-1-3-5-17)24-12-10-23(11-13-24)14-15-27-16-20(25)26/h1-9,21H,10-16H2,(H,25,26)/t21-/m1/s1
IUPAC Name
2-(2-{4-[(R)-(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethoxy)acetic acid
SMILES
OC(=O)COCCN1CCN(CC1)[C@H](C1=CC=CC=C1)C1=CC=C(Cl)C=C1

Pharmacology

Indication

Levocetirizine is indicated for the relief of symptoms associated with allergic rhinitis (seasonal and perennial) in adults and children 6 years of age and older.

Associated Conditions
Pharmacodynamics
Not Available
Mechanism of action

Levocetirizine, the active enantiomer of cetirizine, is an anti-histamine; its principal effects are mediated via selective inhibition of H1 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 H1-receptor 2-fold higher than that of cetirizine (Ki = 3 nmol/L vs. 6 nmol/L, respectively). This increased affinity has unknown clinical relevance.

TargetActionsOrganism
AHistamine H1 receptor
antagonist
inhibitor
Human
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 Tmax was delayed by about 1.25 hours and Cmax was decreased by about 36% after administration with a high fat meal; therefore, levocetirizine can be administered with or without food.

Volume of distribution

Approximately 0.4 L/kg.

Protein binding

91-92%.

Metabolism

Levocetirizine is poorly metabolized and mostly excreted via the urine [3]. This is favourable as it is unlikely to be modified by drugs administered concomitantly.

Route of elimination

Renal excretion, mainly tubular excretion - therefore dose adjustment may be required in patients with renal impairment. After admininstration of a 5 mg dose of radiolabeled oral levocetirizine - 85.4% was excreted in urine and and 12.9% in feces (146 hours later).

Half life

8-9 hours.

Clearance

about 0.63 mL/kg/min (oral total body clearance).

Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Levocetirizine H1-Antihistamine ActionDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
2,5-Dimethoxy-4-ethylamphetamine2,5-Dimethoxy-4-ethylamphetamine may decrease the sedative activities of Levocetirizine.
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may decrease the sedative activities of Levocetirizine.
3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine may decrease the sedative activities of Levocetirizine.
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may decrease the sedative activities of Levocetirizine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when Levocetirizine is combined with 7-Nitroindazole.
AcepromazineThe risk or severity of adverse effects can be increased when Levocetirizine is combined with Acepromazine.
AceprometazineThe risk or severity of adverse effects can be increased when Levocetirizine is combined with Aceprometazine.
AcetaminophenAcetaminophen may decrease the excretion rate of Levocetirizine which could result in a higher serum level.
AcetazolamideThe risk or severity of adverse effects can be increased when Levocetirizine is combined with Acetazolamide.
Acetyl sulfisoxazoleThe metabolism of Levocetirizine can be decreased when combined with Acetyl sulfisoxazole.
Food Interactions
Not Available

References

General References
  1. Grant JA, Riethuisen JM, Moulaert B, DeVos C: A double-blind, randomized, single-dose, crossover comparison of levocetirizine with ebastine, fexofenadine, loratadine, mizolastine, and placebo: suppression of histamine-induced wheal-and-flare response during 24 hours in healthy male subjects. Ann Allergy Asthma Immunol. 2002 Feb;88(2):190-7. [PubMed:11868924]
  2. Ferrer M: Pharmacokinetic evaluation of levocetirizine. Expert Opin Drug Metab Toxicol. 2011 Aug;7(8):1035-47. doi: 10.1517/17425255.2011.590131. Epub 2011 Jun 4. [PubMed:21639816]
  3. Devillier P, Roche N, Faisy C: Clinical pharmacokinetics and pharmacodynamics of desloratadine, fexofenadine and levocetirizine : a comparative review. Clin Pharmacokinet. 2008;47(4):217-30. [PubMed:18336052]
External Links
Human Metabolome Database
HMDB0240226
KEGG Drug
D07402
PubChem Compound
1549000
PubChem Substance
310264866
ChemSpider
1266001
BindingDB
85030
ChEBI
94559
ChEMBL
CHEMBL1201191
HET
LCR
Drugs.com
Drugs.com Drug Page
Wikipedia
Levocetirizine
ATC Codes
R06AE09 — Levocetirizine
PDB Entries
5dqf
FDA label
Download (167 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableRhinitis, Allergic, Perennial and Seasonal1
1CompletedBasic ScienceHealthy Volunteers1
1CompletedPreventionSkin Inflammation1
1CompletedTreatmentAllergic Rhinitis (AR)1
1CompletedTreatmentAllergies1
1CompletedTreatmentFasting1
1CompletedTreatmentFasting State1
1CompletedTreatmentFed1
1CompletedTreatmentHealthy Volunteers2
1CompletedTreatmentRhinitis1
2CompletedNot AvailableAllergic Rhinitis (AR)1
2CompletedTreatmentAllergic / Rhinitis / Rhinitis, Allergic, Seasonal / Seasonal1
2CompletedTreatmentCoughing1
2CompletedTreatmentNeoplasms, Colorectal1
3CompletedNot AvailableAtopic Dermatitis (AD)1
3CompletedTreatmentAllergic Rhinitis (AR)2
3CompletedTreatmentAllergic Rhinitis (AR) / Chronic Urticaria2
3CompletedTreatmentAllergic / Perennial / Rhinitis1
3CompletedTreatmentAllergic / Rhinitis / Seasonal1
3CompletedTreatmentDermatitis, Eczematous / Skin Inflammation1
3CompletedTreatmentPerennial Allergic Rhinitis (PAR)1
3CompletedTreatmentRhinitis1
3CompletedTreatmentRhinitis, Allergic, Seasonal2
3CompletedTreatmentUrticarias2
3CompletedTreatmentVasomotor Rhinitis1
3Not Yet RecruitingTreatmentAngiœdema / Urticarias1
3TerminatedTreatmentAsthma Bronchial1
4CompletedNot AvailableAnti-allergic Agents1
4CompletedNot AvailableRhinitis, Allergic, Perennial2
4CompletedNot AvailableSeasonal Allergic Rhinitis (SAR)1
4CompletedBasic ScienceHealthy Volunteers1
4CompletedTreatmentAllergic Rhinitis (AR)5
4CompletedTreatmentAllergic / Perennial / Rhinitis1
4CompletedTreatmentAtopic Dermatitis (AD) / Pruritus1
4CompletedTreatmentChronic Idiopathic Urticaria1
4CompletedTreatmentChronic Urticaria1
4CompletedTreatmentHypersensitivity1
4CompletedTreatmentPerennial Allergic Rhinitis (PAR)2
4CompletedTreatmentRhinitis, Allergic, Seasonal2
4CompletedTreatmentSeasonal Allergic Rhinitis (SAR)2
4Unknown StatusTreatmentChronic Idiopathic Urticaria / Urticarias1
4Unknown StatusTreatmentPerennial Allergic Rhinitis (PAR)1
Not AvailableCompletedNot AvailableRhinitis, Allergic, Perennial and Seasonal1
Not AvailableCompletedTreatmentRhinitis, Allergic, Seasonal1
Not AvailableTerminatedNot AvailableRhinitis / Urticarias1
Not AvailableUnknown StatusDiagnosticAsthma Bronchial / Asthma, Allergic / Non-allergic Asthma1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Kit
Tablet, coatedOral5 mg/1
Tablet, film coatedOral5 mg/1
KitTopical
SolutionOral0.5 mg/1mL
TabletOral5 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5698558No1993-03-242013-03-24Us
US8633194No2007-10-162027-10-16Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0658 mg/mLALOGPS
logP2.98ALOGPS
logP0.87ChemAxon
logS-3.8ALOGPS
pKa (Strongest Acidic)3.59ChemAxon
pKa (Strongest Basic)7.42ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area53.01 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity106.87 m3·mol-1ChemAxon
Polarizability41.93 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-000i-0019000000-e24b60aef9a19aa0ca89
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0udi-0090000000-4fbbabe7bf3d0ad4cab5
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0udi-0190000000-8783499dc5c2d31a3f7a
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0uxr-0790000000-4efaf73700a535eb98e9
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-014i-0920000000-f952b59e46cde6d2cfac
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0udi-0492000000-90537be4971a327c0fb1

Taxonomy

Description
This compound belongs to the class of organic compounds known as diphenylmethanes. These are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Diphenylmethanes
Direct Parent
Diphenylmethanes
Alternative Parents
N-alkylpiperazines / Chlorobenzenes / Aralkylamines / Aryl chlorides / Trialkylamines / Amino acids / Monocarboxylic acids and derivatives / Dialkyl ethers / Carboxylic acids / Azacyclic compounds
show 5 more
Substituents
Diphenylmethane / Chlorobenzene / Halobenzene / N-alkylpiperazine / Aralkylamine / Aryl halide / 1,4-diazinane / Aryl chloride / Piperazine / Amino acid
show 22 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
Inhibitor
General Function
Histamine receptor activity
Specific Function
In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamin...
Gene Name
HRH1
Uniprot ID
P35367
Uniprot Name
Histamine H1 receptor
Molecular Weight
55783.61 Da
References
  1. Ferrer M: Pharmacokinetic evaluation of levocetirizine. Expert Opin Drug Metab Toxicol. 2011 Aug;7(8):1035-47. doi: 10.1517/17425255.2011.590131. Epub 2011 Jun 4. [PubMed:21639816]
  2. Devillier P, Roche N, Faisy C: Clinical pharmacokinetics and pharmacodynamics of desloratadine, fexofenadine and levocetirizine : a comparative review. Clin Pharmacokinet. 2008;47(4):217-30. [PubMed:18336052]

Drug created on March 19, 2008 10:21 / Updated on October 01, 2018 16:37