Latanoprost

S01E - Antiglaucoma preparations and miotics ATC S01EE01 Small molecule approved 1996 Topical Prodrug Natural product

Active form: Latanoprost Acid.

JFDA label: Xalatan eye drops

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

Hypersensitivity to latanoprost, benzalkonium chloride, 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

Cardiac disorders (2)

Common Angina pectoris · chest pain

Skin and subcutaneous tissue disorders (3)

Common allergic skin reaction · Erythema of eyelid · skin rash

Musculoskeletal and connective tissue disorders (3)

Common Arthralgia · back pain · myalgia

Eye disorders (14)

Common blurred vision · burning sensation of eyes · conjunctival hyperemia · crusting of eyelid · dry eye syndrome · Epithelial keratopathy · eye pain · eye pruritus · eyelid edema · eyelid pain · iris hyperpigmentation · lacrimation · photophobia · stinging of eyes

Infections and infestations (1)

Common Influenza

Other (1)

Very Common Central nervous system: Foreign body sensation of eye

Respiratory, thoracic and mediastinal disorders (2)

Common Nasopharyngitis · upper respiratory tract infection

Dosing

Source: Lexicomp

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

Refer to adult dosing.

There is 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.

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:

Herpetic keratitis

Use with caution in patients with a history of herpes simplex keratitis; reactivation may occur. Avoid use in patients with active herpes simplex keratitis.

Ocular disease

Use with caution in aphakic patients, pseudophakic patients with a torn posterior lens capsule, or patients with risk factors for macular edema. Safety and efficacy have not been determined for use in patients with angle-closure, inflammatory, or neovascular glaucoma. 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

FDA category C

Adverse events were observed in animal reproduction studies at maternally toxic doses.

Lactation

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

Monitoring

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

Chemistry & Properties

Formula	C26H40O5
Molecular weight	432.6 g/mol
IUPAC name	propan-2-yl (Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(3R)-3-hydroxy-5-phenylpentyl]cyclopentyl]hept-5-enoate
CAS	130209-82-4
PubChem CID	5311221
InChIKey	`GGXICVAJURFBLW-CEYXHVGTSA-N`
logP	4.19 (XLogP 4.3)
Polar surface area	86.99 Å²
H-bond acceptors / donors	5 / 3
Drug-likeness (QED)	0.25
Lipinski violations	0

SMILES

CC(C)OC(=O)CCC/C=C\C[C@@H]1[C@@H](CC[C@@H](O)CCc2ccccc2)[C@H](O)C[C@@H]1O

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	70.0%
Half-life	0.713 h
Volume of distribution	0.187 L/kg
Protein binding	87.2%
BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP2C8	Inhibitor	—
CYP3A4	Inhibitor	—

Receptor binding (top 4)

Target	Action	Affinity
Prostaglandin F (PTGFR)	Binding	pKi 7.4
FP receptor (PTGFR)	Agonist	pKi 6.3
Prostaglandin E1 (PTGER1)	Binding	pKi 5.4
Prostaglandin E3 (PTGER3)	Binding	pKi 5.2

Transporters

ASBT (Inhibitor)BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)MRP2 (Inhibitor)MRP4 (Inhibitor)OAT1 (Inhibitor)OAT3 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OATP2B1 (Inhibitor)P-gp (Inhibitor)OATP2B1 (Substrate)P-gp (Substrate)

Registered Products (7)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
LATAZ-CO	Injection 5 mg/ml, 50 mcg/ml	2.5 ml	Sun Set Drug Store	3.190
Xalacom Eye Drops	Ophthalmic Solution 5 mg, 50 mcg	2.5 ml	Khoury Drug Store	4.190
Lataz	Solution 0.005 %	2.5 ml	Sun Set Drug Store	4.420
Loprostan Eye Drops	Ophthalmic Solution as Maleate 0.50 %, 0.005 %	2.5 ml	Amman Pharmaceutical Indusries	4.780
Normoprost	Injection 50 mcg/ml	3 ml	Nabulsi Drug Store	4.860
Xalatan eye drops	Ophthalmic Solution 50 mcg/ml	2.5 ml	Khoury Drug Store	5.780
Loprost Eye Drops	Ophthalmic Solution 0.005 %	2.5 ml	Amman Pharmaceutical Indusries	6.120