Zultan

Approved Indications:

• Open-Angle Glaucoma (OAG): Indicated for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma.
• Ocular Hypertension (OHT): Indicated for lowering IOP in patients with ocular hypertension.

Clinically Accepted Off-label Uses:

• Currently, there are no well-established off-label indications for latanoprostene bunod. Its use is limited to lowering IOP in the management of open-angle glaucoma and ocular hypertension.

Adults (including Elderly):

• Recommended Dose: One drop in the affected eye(s) once daily in the evening.
• Route of Administration: Ophthalmic (topical).
• Important Note: Do not exceed once-daily dosing, as more frequent administration may decrease the IOP-lowering effect.

Pediatric Use:

• Safety and efficacy in pediatric patients under 16 years of age have not been established.

Hepatic or Renal Impairment:

• No dose adjustment is necessary; however, caution is advised due to limited clinical data in these populations.

Administration Instructions:

• Remove contact lenses prior to administration. Reinsert lenses at least 15 minutes after instillation.
• If more than one topical ophthalmic product is being used, administer each at least 5 minutes apart.
• Do not allow the dropper tip to touch any surface to avoid contamination.

Latanoprostene bunod is a nitric oxide (NO)-donating prostaglandin F2α analog. After administration, it is metabolized into two active moieties: latanoprost acid and butanediol mononitrate. Latanoprost acid increases aqueous humor outflow through the uveoscleral pathway, while nitric oxide released from butanediol mononitrate enhances trabecular meshwork outflow by relaxing the trabecular meshwork and Schlemm’s canal. This dual mechanism results in a significant and sustained reduction in intraocular pressure.

• Absorption: Rapidly absorbed through the cornea and hydrolyzed into latanoprost acid and nitric oxide–releasing components.
• Bioavailability: Minimal systemic exposure; pharmacologic effects are localized to ocular tissues.
• Distribution: Primarily retained in ocular tissues; negligible systemic distribution.
• Metabolism:
• Latanoprost acid undergoes hepatic β-oxidation.
• Butanediol mononitrate decomposes to release nitric oxide and inactive metabolites.
• Elimination:
• Metabolites are eliminated mainly via the kidneys.
• Half-life:
• Latanoprost acid: ~17 minutes in plasma
• Nitric oxide: very short half-life with local activity only
• Onset of Action: Within 1 to 3 hours
• Peak Effect: Approximately 8 to 12 hours after administration
• Duration of Action: Maintains IOP reduction for approximately 24 hours

Pregnancy:

• FDA Pregnancy Category (Not assigned): Based on animal data, latanoprostene bunod may pose fetal risk. No adequate, well-controlled studies in pregnant women exist. Use during pregnancy only if clearly needed.

Lactation:

• It is unknown whether latanoprostene bunod or its metabolites are excreted in human breast milk.
• Caution is advised when administering to nursing mothers. Consider discontinuing breastfeeding or the drug, depending on the clinical necessity.

• Primary Class: Ophthalmic Antiglaucoma Agent
• Subclasses:
• Prostaglandin F2α Analog
• Nitric Oxide Donor

• Known hypersensitivity to latanoprostene bunod or any component of the formulation
• Active intraocular inflammation (e.g., uveitis)
• Aphakia or pseudophakia with a torn posterior lens capsule (increased risk of macular edema)
• History of herpetic keratitis

• Iris Pigmentation: May cause gradual, permanent increase in brown pigmentation of the iris, especially in mixed-color irides.
• Eyelash and Eyelid Changes: Eyelash growth, thickening, and eyelid skin darkening may occur.
• Macular Edema: Use with caution in aphakic patients or those with posterior capsule rupture.
• Intraocular Inflammation: May exacerbate or reactivate uveitis or herpes simplex keratitis.
• Systemic Effects: Though rare, systemic exposure may cause mild muscle or joint pain.
• Contact Lenses: Contains benzalkonium chloride, which may be absorbed by soft contact lenses and cause discoloration or irritation.

Common (≥1%):

• Ocular: Conjunctival hyperemia, eye irritation, eye pain, blurred vision, foreign body sensation, increased eyelash length
• Systemic: Headache, mild musculoskeletal discomfort

Less Common (<1%):

• Eyelid skin darkening, photophobia, dry eye, corneal changes

Serious (Rare):

• Macular edema
• Uveitis
• Reactivation of herpes simplex keratitis
• Severe ocular inflammation

Timing and Severity:

• Most side effects are mild to moderate and occur within the first few weeks of use.
• Pigmentary changes are usually gradual and permanent.
• Systemic adverse effects are rare due to minimal systemic absorption.

• Other Prostaglandin Analogs (e.g., bimatoprost, travoprost): Concurrent use may reduce IOP-lowering efficacy and increase risk of adverse effects.
• Topical NSAIDs: May interfere with the prostaglandin-mediated IOP-lowering effect; monitor IOP if used concurrently.
• Systemic Drug Interactions: Unlikely due to minimal systemic absorption.
• Enzyme Involvement: Does not significantly interact with CYP450 enzymes.

• FDA Approval: Latanoprostene bunod is approved in the U.S. as a first-line agent for open-angle glaucoma and ocular hypertension.
• Clinical Guidelines (AAO, EGS, NICE): Recognized as a novel dual-mechanism option with better IOP reduction than traditional prostaglandins in some patients.
• Practice Trends: Increasingly recommended for patients who require more aggressive IOP control or are unresponsive to single-pathway agents.
• Formulation Innovation: First FDA-approved prostaglandin analog combined with nitric oxide donor for enhanced outflow through both trabecular and uveoscleral pathways.

• Before Opening: Store in a refrigerator at 2°C to 8°C.
• After Opening: May be stored at room temperature up to 25°C for up to 8 weeks.
• Do Not Freeze.
• Light Sensitivity: Protect from light.
• Handling Instructions: Keep the bottle tightly closed. Avoid touching the dropper tip to prevent contamination.