Levocabastine

S01G - Decongestants and antiallergics ATC R01AC02 Small molecule approved 1993 Topical

JFDA label: AZORA Metered Dose Nasal Spray

Mechanism of Action

Potent, selective histamine H1-receptor antagonist

Indications

Approved

Allergic rhinitis

Contraindications

Source: Lexicomp

Hypersensitivity to levocabastine or any component of the formulation 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 (1)

Common Fatigue

Eye disorders (1)

Common Eye irritation

General disorders and administration site conditions (4)

Common Application site burning · application site irritation · application site pain · application site reaction (dryness, discomfort)

Respiratory, thoracic and mediastinal disorders (3)

Common Epistaxis · pharyngolaryngeal pain · sinusitis

Dosing

Source: Lexicomp

Allergic rhinitis: Adults ≤65 years: Intranasal: Two sprays in each nostril twice daily; if necessary, may increase dose to 2 sprays 3 to 4 times daily; consider therapy discontinuation if no response within 3 days. Continuous treatment >10 weeks has not been evaluated.

Allergic rhinitis: Children ≥12 years and Adolescents: Intranasal: Refer to adult dosing.

There are no dosage adjustments provided in the manufacturer's labeling; use with caution.

There are no dosage adjustments provided in the manufacturer's labeling.

Warnings & Precautions

Source: Lexicomp

Renal impairment

Use caution; limited data available regarding use in this population.

Pregnancy & Lactation

Pregnancy

Adverse events were observed in some animal reproduction studies when using oral doses much larger than the equivalent maximum human nasal dose.

Lactation

Following intranasal application, minute amounts of levocabastine have been detected in human breast milk (Simons 1999). The manufacturer recommends that caution be exercised when administering levocabastine to nursing women.

Chemistry & Properties

Formula	C26H29FN2O2
Molecular weight	420.53 g/mol
IUPAC name	(3S,4R)-1-[4-cyano-4-(4-fluorophenyl)cyclohexyl]-3-methyl-4-phenylpiperidine-4-carboxylic acid
CAS	79516-68-0
PubChem CID	54385
InChIKey	`ZCGOMHNNNFPNMX-KYTRFIICSA-N`
logP	4.89 (XLogP 2.5)
Polar surface area	64.33 Å²
H-bond acceptors / donors	3 / 1
Drug-likeness (QED)	0.76
Lipinski violations	0

SMILES

C[C@@H]1CN([C@H]2CC[C@](C#N)(c3ccc(F)cc3)CC2)CC[C@]1(C(=O)O)c1ccccc1

Biology & Pharmacokinetics

Pharmacokinetics

BBB penetrant	Yes

Enzyme interactions

Enzyme	Role	Detail
CYP3A4	Substrate	—

Receptor binding (top 1)

Target	Action	Affinity
NTS2 receptor (NTSR2)	Agonist	pKi 6.8

Transporters

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

Registered Products (2)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
AZORA Eye Drops	Ophthalmic Solution 0.054 %	4 ml pack varies	Amman Pharmaceutical Industries Co	6.360
AZORA Metered Dose Nasal Spray	Spray 0.054 %	10 ml pack varies	Amman Pharmaceutical Industries Co	6.450