Latanoprostene Bunod

S01E - Antiglaucoma preparations and miotics ATC S01EE06 Small molecule approved 2017 Topical Natural product

JFDA label: Vyzulta

Mechanism of Action

Agonist of Prostaglandin F2-alpha receptor — Prostanoid FP receptor agonist

Target	Action	Gene / class
Prostaglandin F2-alpha receptor efficacy	AGONIST	PTGFR

Indications

Approved

Elevated intraocular pressure

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

Eye disorders (3)

Common Conjunctival hyperemia · eye irritation · eye pain

General disorders and administration site conditions (1)

Common Application site pain

Dosing

Source: Lexicomp

Elevated intraocular pressure: Ophthalmic: Instill 1 drop into affected eye(s) once daily in the evening; do not exceed the once daily dosage (may decrease the IOP-lowering effect)

Adolescents >16 years: Refer to adult dosing.

Refer to adult dosing.

Warnings & Precautions

Source: Lexicomp

Bacterial keratitis

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

Ocular effects

May change/increase brown pigmentation of the iris, the eyelid skin, and eyelashes; length and/or number of eyelashes may also be increased. Pigmentation of the iris is likely to be permanent, although iris color change may not be noticeable for months to years; pigmentation of the periorbital tissue and eyelash changes may be reversible following discontinuation of therapy. Long-term consequences and potential injury to eye are not known.

Ocular inflammation

Intraocular inflammation and exacerbation of inflammation may occur; use with caution in patients with a history of intraocular inflammation (eg, iritis/uveitis) and generally avoid use in patients with active intraocular inflammation. Disease-related concerns:

Ocular disease

Use with caution in aphakic patients, pseudophakic patients with a torn posterior lens capsule, or patients with risk factors for macular edema (macular edema, including cystoid macular edema, has been reported during treatment with prostaglandin analogs). Special populations:

Contact lens wearers

Contains benzalkonium chloride, which may be absorbed by contact lenses; remove contacts prior to administration and wait 15 minutes before reinserting.

Pregnancy & Lactation

Pregnancy

Adverse events were observed in animal reproduction studies. Agents other than latanoprostene bunod may be preferred in pregnant women (Prum 2016; Sethi 2016).

Lactation

It is not known if latanoprostene bunod is present in breast milk following ocular application. According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. When treatment with an ophthalmic agent is needed, the minimum effective dose should be used in combination with punctual occlusion to decrease potential systemic exposure (Sethi 2016).

Monitoring

Clinical pearl	IOP; regularly examine patients who develop increased iris pigmentation

Chemistry & Properties

Formula	C27H41NO8
Molecular weight	507.62 g/mol
IUPAC name	4-nitrooxybutyl (Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(3R)-3-hydroxy-5-phenylpentyl]cyclopentyl]hept-5-enoate
CAS	860005-21-6
PubChem CID	11156438
InChIKey	`LOVMMUBRQUFEAH-UIEAZXIASA-N`
logP	3.77 (XLogP 4.4)
Polar surface area	139.36 Å²
H-bond acceptors / donors	8 / 3
Drug-likeness (QED)	0.09
Lipinski violations	1

SMILES

O=C(CCC/C=C\C[C@@H]1[C@@H](CC[C@@H](O)CCc2ccccc2)[C@H](O)C[C@@H]1O)OCCCCO[N+](=O)[O-]

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	70.0%
Half-life	0.633 h
Volume of distribution	0.203 L/kg
Protein binding	89.0%
BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP2C19	Inhibitor	—
CYP2C19	Substrate	—
CYP2C8	Inhibitor	—
CYP2C9	Inhibitor	—
CYP3A4	Inhibitor	—
CYP3A4	Substrate	—

Receptor binding (top 1)

Target	Action	Affinity
FP receptor (PTGFR)	Agonist	pKi 8.6

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)OATP2B1 (Substrate)P-gp (Substrate)

Registered Products (1)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Vyzulta	Solution 0.024 %	5 ml	Petra Drug Store	15.210