Latanoprost

Generic Name: Latanoprost
Pharmacological Class: Prostaglandin F2α analogue
Therapeutic Class: Antiglaucoma agent
ATC Code: S01EE01
Common Brand Names: Xalatan, Monopost (preservative-free), Xalacom (with timolol), Latacom (with timolol)
Legal Classification: Prescription-only (Rx)
Formulations: Ophthalmic solution (0.005%, equivalent to 50 mcg/mL)
Route of Administration: Topical (ocular use only)

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Chemical and Pharmacological Overview

• Molecular Formula: C26H40O5

• Molecular Weight: 432.6 g/mol

• Chemical Nature: Isopropyl ester prodrug of latanoprost acid (active form)

• Lipid Solubility: High, facilitates corneal penetration

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Mechanism of Action

Latanoprost is a synthetic analog of prostaglandin F2α that:

• Reduces intraocular pressure (IOP) by increasing the outflow of aqueous humor primarily through the uveoscleral pathway (non-conventional route).

• It does not significantly affect aqueous humor production or trabecular outflow.

• After corneal absorption, latanoprost is hydrolyzed to latanoprost acid, its active form.

This pharmacodynamic action helps prevent optic nerve damage in glaucoma by reducing IOP.

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Therapeutic Indications

Approved indications:

1. Open-angle glaucoma

2. Ocular hypertension

   • In adults and children ≥1 year where IOP is elevated and needs reduction

3. Chronic angle-closure glaucoma (with patent iridotomy, off-label in some jurisdictions)

Combination products are used when additional IOP reduction is needed beyond monotherapy (e.g., Latanoprost + Timolol).

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Dosage and Administration

Standard Adult Dose:

• One drop in the affected eye(s) once daily in the evening

• Maximum efficacy occurs when used regularly in the evening

• Do not exceed once-daily dosing; more frequent dosing reduces efficacy

Pediatric Use:

• Same dosing as adults

• Approved for use in children ≥1 year

Administration Notes:

• Remove contact lenses before use; reinsert after 15 minutes

• Use with caution in aphakic patients or pseudophakic patients with a torn posterior lens capsule

• Separate from other eye drops by at least 5 minutes

• Minimize systemic absorption by punctual occlusion (pressing nasolacrimal duct) for 1–2 minutes

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Pharmacokinetics

• Absorption: Rapid through cornea; converted to active acid form

• Peak IOP reduction: ~8–12 hours post-dose

• Duration of action: ≥24 hours

• Half-life: Plasma half-life of latanoprost acid is ~17 minutes

• Systemic exposure: Minimal; blood levels are undetectable within 1 hour

• Excretion: Primarily via kidneys as metabolites

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Contraindications

• Known hypersensitivity to latanoprost or any component of the formulation

• Pregnancy Category C (caution advised)

• Not to be used while wearing contact lenses (due to benzalkonium chloride)

• Patients with active intraocular inflammation (e.g., uveitis)

• Caution in herpetic keratitis, especially with a history of recurrence

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Warnings and Precautions

1. Iris pigmentation changes:

   • Permanent brown pigmentation of the iris, especially in patients with mixed-color irides (hazel, green-brown)

   • Usually visible within months of treatment initiation

   • No known harmful effects, but usually irreversible

   • Does not progress after drug discontinuation

2. Eyelash and eyelid changes:

   • Increased length, thickness, pigmentation, and number of lashes

   • Hyperpigmentation of eyelid skin may also occur

3. Cystoid macular edema:

   • Especially in aphakic/pseudophakic patients or with macular disease

   • Caution in diabetic patients

4. Herpes simplex virus keratitis:

   • May be reactivated

   • Avoid use in active or recurrent HSV ocular infections

5. Intraocular inflammation:

   • Risk of exacerbation in uveitis or iritis

   • Avoid use if active inflammation is present

6. Bacterial keratitis risk:

   • Contamination of multi-dose eye drop bottles may occur

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Adverse Effects

Very Common (>10%):

• Iris pigmentation (10–20% of users, increasing with longer use)

Common (1–10%):

• Eyelash growth changes

• Eye irritation (burning, stinging)

• Conjunctival hyperemia

• Eyelid skin darkening

• Dry eyes

• Foreign body sensation

• Eye pain

Uncommon (0.1–1%):

• Cystoid macular edema

• Blurred vision

• Photophobia

• Headache

• Dizziness

Rare (<0.1%):

• Herpes keratitis

• Uveitis/iritis

• Asthma exacerbation

• Skin rash or hypersensitivity reactions

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Drug Interactions

• Other prostaglandin analogs (e.g., travoprost, bimatoprost):

  • Avoid co-administration due to risk of paradoxical IOP increase

• NSAIDs:

  • May reduce the IOP-lowering effect; caution in concurrent use

• Preservative interactions:

  • Benzalkonium chloride can interact with soft contact lenses; delay re-insertion by 15 minutes

No major systemic drug interactions due to minimal systemic absorption.

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Use in Pregnancy and Lactation

Pregnancy:

• Category C (FDA)

• Animal studies show adverse fetal effects; human data are lacking

• Use only if potential benefit outweighs risk

Lactation:

• Unknown if excreted in human milk

• Likely low systemic exposure, but caution recommended

• Avoid breastfeeding or consider alternative treatment if necessary

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Special Populations

• Pediatrics: Approved in children ≥1 year; similar efficacy and safety as adults

• Elderly: No dosage adjustment needed

• Hepatic/Renal Impairment: No dose adjustment; systemic exposure negligible

• Contact lens users: Remove lenses before instillation; reinsert after 15 minutes

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Comparison with Other Prostaglandin Analogues

Agent	Onset/Duration	Pigmentation Risk	Lash Growth	Preservative-Free Option
Latanoprost	3–4 hrs / 24 hrs	Yes	Yes	Yes (Monopost)
Bimatoprost	2 hrs / 24 hrs	Higher	Pronounced	Yes
Travoprost	2 hrs / 24 hrs	Moderate	Moderate	Yes
Tafluprost	2–4 hrs / 24 hrs	Lower	Moderate	Yes

Latanoprost is often first-line due to high efficacy, once-daily dosing, and long-term tolerability.

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Monitoring Parameters

• Intraocular pressure (IOP): Baseline, then routinely (2–4 weeks after initiation)

• Ocular surface health: Signs of irritation, dryness, or infection

• Iris pigmentation: Document baseline and monitor for changes

• Lash changes and periorbital effects

• Macular status in at-risk patients (diabetics, aphakic)

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Patient Counseling Information

• Use exactly as prescribed, even if eye feels fine

• Administer once daily in the evening

• Wash hands before use; avoid touching the dropper tip

• Remove contact lenses prior to use and reinsert after 15 minutes

• Apply gentle pressure to the inner corner of the eye for 1–2 minutes to reduce systemic absorption

• Do not use more than once daily

• Inform provider about eye changes like color, lashes, discomfort

• Store in refrigerator before opening; can be stored at room temperature up to 6 weeks after opening

• Discard the bottle 4 weeks after opening

• If using multiple eye drops, space them 5 minutes apart