Epinastine

S01G - Decongestants and antiallergics ATC S01GX10 Small molecule approved 2003 Topical Natural product

JFDA label: Relestat Eye drops solution

Mechanism of Action

Selective H1-receptor antagonist; inhibits release of histamine from the mast cell; also has affinity for the H2, alpha1, alpha2, and the 5-HT2 receptors

Indications

Approved

Eye Manifestations — eye allergy
Hypersensitivity — allergic disease

Off-label

Rhinitis, Allergic, Perennial
Rhinitis, Allergic, Seasonal

Contraindications

Source: Lexicomp

There are no contraindications listed in the manufacturer's labeling 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 Headache

Eye disorders (4)

Common Burning sensation of eyes · eye pruritus · follicular conjunctivitis · ocular hyperemia

Infections and infestations (1)

Common Infection

Respiratory, thoracic and mediastinal disorders (4)

Common Cough · pharyngitis · rhinitis · sinusitis

Dosing

Source: Lexicomp

Allergic conjunctivitis: Ophthalmic: Instill 1 drop into each eye twice daily. Continue throughout period of exposure, even in the absence of symptoms.

(For additional information see "Epinastine: Pediatric drug information") Allergic conjunctivitis: Ophthalmic: Children ≥2 years: Refer to adult dosing.

Refer to adult dosing.

No dosage adjustment provided in manufacturer's labeling. However, dosage adjustment unlikely due to low systemic absorption.

Warnings & Precautions

Source: Lexicomp

Bacterial keratitis

Inadvertent contamination of multiple-dose ophthalmic solutions has caused bacterial keratitis. Special populations:

Contact lens wearers

Contains benzalkonium chloride which may be absorbed by contact lenses; remove contact lenses prior to use and wait 10 minutes before reinserting. Other warnings/precautions:

Appropriate use

For topical ophthalmic use only. Not for the treatment of contact lens irritation; do not wear contact lenses if eye is red.

Pregnancy & Lactation

Pregnancy

FDA category C Teratogenic

Teratogenic effects were not observed in animal studies. There are no adequate and well-controlled studies in pregnant women.

Lactation

It is not known if epinastine is excreted in breast milk. The manufacturer recommends that caution be exercised when administering epinastine to nursing women.

Chemistry & Properties

Formula	C16H15N3
Molecular weight	249.32 g/mol
IUPAC name	2,4-diazatetracyclo[12.4.0.02,6.07,12]octadeca-1(18),3,7,9,11,14,16-heptaen-3-amine
CAS	80012-43-7
PubChem CID	3241
InChIKey	`WHWZLSFABNNENI-UHFFFAOYSA-N`
logP	2.47 (XLogP 3.5)
Polar surface area	41.62 Å²
H-bond acceptors / donors	3 / 1
Drug-likeness (QED)	0.78
Lipinski violations	0

SMILES

NC1=NCC2c3ccccc3Cc3ccccc3N12

Biology & Pharmacokinetics

Pharmacokinetics

BBB penetrant	Yes (logBB -0.16)

Enzyme interactions

Enzyme	Role	Detail
CYP1A2	Inhibitor	—
CYP1A2	Substrate	—
CYP2B6	Substrate	—
CYP2C19	Substrate	—
CYP2C9	Inhibitor	—
CYP2C9	Substrate	—
CYP2D6	Inhibitor	—
CYP2D6	Substrate	—
CYP3A4	Substrate	—

Receptor binding (top 1)

Target	Action	Affinity
H1 receptor (HRH1)	Antagonist	pIC50 7.6

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)MATE1 (Inhibitor)MATE2 (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OCT2 (Inhibitor)P-gp (Inhibitor)MDR1 (Substrate)P-gp (Substrate)

Registered Products (2)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Apistat Eye Drop	Ophthalmic Solution 0.5 mg/ml	5 ml	Amman Pharmaceutical Indusries	4.470
Relestat Eye drops solution	Solution 0.5 mg/ml	5 ml	Arab Company for Medical & Agricultural Products	5.530