Levocetirizine

R06A - Antihistamines for systemic use ATC R06AE09 Small molecule approved 2007 Oral Natural product

JFDA label: Xyzal Tab

Mechanism of Action

Levocetirizine is an antihistamine which selectively competes with histamine for H1-receptor sites on effector cells in the gastrointestinal tract, blood vessels, and respiratory tract. Levocetirizine, the active enantiomer of cetirizine, has twice the binding affinity at the H1-receptor compared to cetirizine.

Indications

Approved

Allergic rhinitis (OTC only)
Chronic idiopathic urticaria
Perennial allergic rhinitis

Contraindications

Source: Lexicomp

Known hypersensitivity to levocetirizine, cetirizine, or any component of the formulation Absolute
end-stage renal disease (CrCl Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Nervous system disorders (2)

Common Drowsiness · fatigue

Gastrointestinal disorders (3)

Common Constipation · vomiting · xerostomia

Ear and labyrinth disorders (1)

Common Otitis media

General disorders and administration site conditions (1)

Common Fever

Other (2)

Very Common Gastrointestinal: Diarrhea

Not Known Neuromuscular & skeletal: Weakness

Respiratory, thoracic and mediastinal disorders (4)

Common cough · epistaxis · Nasopharyngitis · pharyngitis

Dosing

Source: Lexicomp

Chronic idiopathic urticaria: Oral: 5 mg once daily (in the evening); some patients may experience relief of symptoms with 2.5 mg once daily. In one clinical trial, the titrated use of higher doses (up to 10 mg twice daily) in adults demonstrated clinical improvement (Staevska 2010). Allergic rhinitis (OTC only): Oral: 5 mg once daily (in the evening); some patients with less severe symptoms may experience relief with 2.5 mg once daily; maximum dose: 5 mg/day

(For additional information see "Levocetirizine: Pediatric drug information") Chronic idiopathic urticaria: Oral: Children 6 months to 5 years: 1.25 mg once daily (in the evening); maximum dose: 1.25 mg/day Children 6 to 11 years: 2.5 mg once daily (in the evening); maximum dose: 2.5 mg/day Children ≥12 years and Adolescents: Oral: 5 mg once daily (in the evening); some patients may experience relief of symptoms with 2.5 mg once daily. Perennial allergic rhinitis: Oral: Children 6 months to 2 years: 1.25 mg once daily (in the evening); maximum dose: 1.25 mg/day Allergic rhinitis (OTC only): Oral: Children 2 to 5 years: 1.25 mg once daily (in the evening); maximum dose: 1.25 mg/day Children 6 to 11 years: 2.5 mg once daily (in the evening); maximum dose: 2.5 mg/day Children ≥12 years and Adolescents: Refer to adult dosing.

Refer to adult dosing; dosing should begin at the lower end of the dosing range.

Chronic idiopathic urticaria, perennial allergic rhinitis: Children ≥12 years, Adolescents, and Adults: CrCl 50 to 80 mL/minute: 2.5 mg once daily CrCl 30 to 50 mL/minute: 2.5 mg once every other day CrCl 10 to 30 mL/minute: 2.5 mg twice weekly (every 3 or 4 days) CrCl Children 6 months to 11 years with renal impairment: Use is contraindicated. Hemodialysis: Nondialyzable Allergic rhinitis (OTC): Use is not recommended.

No dosage adjustment necessary.

Warnings & Precautions

Source: Lexicomp

CNS depression

May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Disease-related concerns:

Renal impairment

Levocetirizine is excreted primarily by the kidneys; use with caution in adults with mild to severe renal impairment; dosage adjustments may be needed. Use is contraindicated in end-stage renal disease (CrCl • Urinary retention: Urinary retention may occur; use with caution in patients with increased risk of urinary retention (including spinal cord lesions or prostatic hyperplasia); discontinue if urinary retention occurs. Concurrent drug therapy issues:

Drug-drug interactions

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:

Elderly

Use with caution in the elderly.

Pregnancy & Lactation

Pregnancy

FDA category B

Adverse events have not been observed in animal reproduction studies; therefore, the manufacturer classifies levocetirizine as pregnancy category B. The use of antihistamines for the treatment of rhinitis during pregnancy is generally considered to be safe at recommended doses. Information related to the use of levocetirizine during pregnancy is limited; therefore, other agents are preferred. Levocetirizine is the active enantiomer of cetirizine; refer to the Cetirizine monograph for additional information.

Lactation

Avoid

It is not known if levocetirizine is excreted in breast milk. Breast-feeding is not recommended by the manufacturer.

Monitoring

Clinical pearl	Creatinine clearance (prior to treatment for dosing adjustment)

Chemistry & Properties

Formula	C21H25ClN2O3
Molecular weight	388.9 g/mol
IUPAC name	2-[2-[4-[(R)-(4-chlorophenyl)-phenylmethyl]piperazin-1-yl]ethoxy]acetic acid
CAS	130018-77-8
PubChem CID	1549000
InChIKey	`ZKLPARSLTMPFCP-OAQYLSRUSA-N`
logP	3.15 (XLogP 1.7)
Polar surface area	53.01 Å²
H-bond acceptors / donors	4 / 1
Drug-likeness (QED)	0.70
Lipinski violations	0

SMILES

O=C(O)COCCN1CCN([C@H](c2ccccc2)c2ccc(Cl)cc2)CC1

Biology & Pharmacokinetics

Pharmacokinetics

BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP2C19	Substrate	—
CYP2D6	Inhibitor	—
CYP3A4	Substrate	—

Receptor binding (top 1)

Target	Action	Affinity
H1 receptor (HRH1)	Antagonist	pKi 8.5

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)OAT4 (Substrate)P-gp (Substrate)

Drug–drug interactions (100+, DDInter)

Interacting drug	Severity	Management
Aldesleukin	moderate
Alfentanil	moderate
Alimemazine	moderate
Alprazolam	moderate
Amitriptyline	moderate
Amobarbital	moderate
Amoxapine	moderate
Apraclonidine	moderate
Aripiprazole	moderate
Asenapine	moderate
Azatadine	moderate
Azelastine (nasal)	moderate
Baclofen	moderate
Benzatropine	moderate
Benzhydrocodone	moderate
Biperiden	moderate
Brexanolone	moderate
Brexpiprazole	moderate
Brimonidine (ophthalmic)	moderate
Brimonidine (topical)	moderate
Brivaracetam	moderate
Brompheniramine	moderate
Buprenorphine	moderate
Bupropion	moderate
Buspirone	moderate
Butabarbital	moderate
Butalbital	moderate
Butorphanol	moderate
Candida albicans	moderate
Cannabidiol	moderate
Carbamazepine	moderate
Carbinoxamine	moderate
Cariprazine	moderate
Carisoprodol	moderate
Cenobamate	moderate
Chloral hydrate	moderate
Chlorcyclizine	moderate
Chlordiazepoxide	moderate
Chlormezanone	moderate
Chlorphenesin	moderate

Showing 40 of 100+.

Registered Products (21)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Layal	Tablet 5 mg	10 tab pack varies	Jordan Sweden Medical & Sterilization Co.	1.550
Lesonal 5mg F.C Tab	Film-Coated Tablet 5 mg	10 tab	UNITED PHARM.MFG.CO.LTD(UPM)/JORDAN	1.550
Levar	Tablet 5 mg	10 tab pack varies	Al-Taqqadom Pharmaceutical Industries	1.550
Xyzal Tab	Tablet 5 mg	10 tab pack varies	Suleiman Tannous & Sons Co. Ltd	1.630
L-Cet 5 Tab	Tablet 5 mg	20 tab pack varies	Noor Drug Store	2.170
Levozal	Tablet 5 mg	20 tab	شركة مستودع ادوية الايمان	2.170
Zolix	Tablet 5 mg	20 tab	Sukhtian Group	2.170
Levosyn	Tablet 5 mg	30 tab	Modern Drug Store	3.080
L-Cet 5 Tab	Tablet 5 mg	30 tab pack varies	Noor Drug Store	3.230
L-Cet	Injection 0.5 mg/ml	100 ml	Noor Drug Store	4.090
Lesonal	Injection 0.5 mg/ml	100 ml	UNITED PHARM.MFG.CO.LTD(UPM)/JORDAN	4.090
Levar	Solution 0.5 mg/1 ml	100 ml	AL-TAQADDOM PHARMACEUTICAL INDUSTRIES/JORDAN	4.090
Layal Syrup	Syrup 2.5 mg/5 ml	100 ml pack varies	Jordan Sweden Medical & Sterilization Co.	4.210
Levar 5mg F.C Tab	Film-Coated Tablet 5 mg	30 tab pack varies	Al-Taqqadom Pharmaceutical Industries	4.370
Cetazal	Tablet 5 mg	30 tab	THE JORDANIAN PHARMACEUTICAL MANUFACTURING COMPANY/JORDAN	4.380
Layal	Tablet 5 mg	30 tab pack varies	Jordan Sweden Medical & Sterilization Co.	4.380
Xyzal Tab	Tablet 5 mg	30 tab pack varies	Suleiman Tannous & Sons Co. Ltd	4.610
Layal Syrup	Syrup 2.5 mg/5 ml	120 ml pack varies	Jordan Sweden Medical & Sterilization Co.	5.050
Zolix 0.5 mg/ml Oral Solution	Solution 0.5 mg/1 ml	200 ml	Sukhtian Group	5.480
HPI-Levocetirizine	Injection 0.5 mg/ml	200 ml	Hayat Pharmaceutical Industries CO.PLC/JORDAN	7.580
Layal Syrup	Syrup 2.5 mg/5 ml	200 ml pack varies	Jordan Sweden Medical & Sterilization Co.	8.000