Xalacom

Approved Indications:

• Open-Angle Glaucoma (OAG): Indicated for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma who are insufficiently responsive to monotherapy with beta-blockers or prostaglandin analogs.
• Ocular Hypertension: Used to lower IOP in patients with ocular hypertension requiring combination therapy.

Clinically Accepted Off-label Uses:

• Normal-Tension Glaucoma: Used in patients with glaucomatous progression despite normal IOP, especially when monotherapy is inadequate.
• Secondary Glaucomas (e.g., Pseudoexfoliative or Pigmentary): Used when dual-mechanism therapy is needed for IOP control.
• Angle-Closure Glaucoma (Post-Iridotomy): Adjunctive treatment in patients with residual IOP elevation after laser iridotomy.

Adults (Including Elderly):

• Recommended Dose: One drop in the affected eye(s) once daily in the evening.
• Route of Administration: Ophthalmic (topical).
• Note: Do not exceed once-daily dosing. More frequent use may reduce efficacy.

Pediatric Use:

• Not recommended in children due to insufficient safety and efficacy data.

Patients with Hepatic Impairment:

• No dosage adjustment is required. Use with caution and monitor for systemic effects.

Patients with Renal Impairment:

• No dose adjustment is generally required. Use cautiously in severe impairment.

Administration Instructions:

• Remove contact lenses before instillation and wait at least 15 minutes before reinserting.
• If using multiple ophthalmic drugs, administer at least 5 minutes apart.
• Avoid touching the dropper tip to any surface to prevent contamination.

Latanoprost is a prostaglandin F2α analog that increases the outflow of aqueous humor through the uveoscleral pathway, leading to a reduction in intraocular pressure. Timolol is a non-selective beta-adrenergic blocker that reduces the formation of aqueous humor by inhibiting beta receptors in the ciliary body. Together, the combination offers a complementary dual mechanism—enhancing outflow and reducing production of aqueous humor—for a more effective and sustained IOP reduction.

• Absorption: Both components are absorbed via the cornea. Latanoprost is rapidly hydrolyzed to its active acid form. Timolol is systemically absorbed to a measurable extent.
• Bioavailability: Latanoprost has low systemic bioavailability. Timolol may enter systemic circulation.
• Distribution: Latanoprost distributes primarily in ocular tissues. Timolol is distributed systemically.
• Metabolism:
• Latanoprost: Metabolized in the liver by beta-oxidation.
• Timolol: Primarily metabolized in the liver via CYP2D6 and other enzymes.
• Elimination:
• Latanoprost: Excreted by the kidneys as inactive metabolites.
• Timolol: Excreted via both renal and hepatic routes.
• Half-life:
• Latanoprost acid (plasma): ~17 minutes
• Timolol (plasma): ~4 to 6 hours
• Onset of Action: Within 1 hour
• Peak Effect: 6 to 12 hours
• Duration of Action: Up to 24 hours

Pregnancy:

• FDA Category C (for both components): Animal studies have shown adverse fetal effects. There are no adequate, well-controlled studies in pregnant women. Use only if the potential benefit justifies the potential risk to the fetus. Avoid use during late pregnancy due to the risk of fetal beta-blockade (from timolol).

Lactation:

• Both latanoprost and timolol may be excreted in human milk.
• Systemic absorption of timolol may cause bradycardia or respiratory effects in breastfed infants.
• Use with caution during breastfeeding. Consider discontinuing nursing or the drug, based on clinical importance.

• Primary Class: Ophthalmic Antiglaucoma Agent
• Subclasses:
• Latanoprost: Prostaglandin F2α Analog
• Timolol: Non-selective Beta-Adrenergic Blocker

• Hypersensitivity to latanoprost, timolol, or any components of the formulation
• Bronchial asthma or history of asthma
• Severe chronic obstructive pulmonary disease (COPD)
• Sinus bradycardia
• Second- or third-degree atrioventricular block
• Overt cardiac failure
• Cardiogenic shock
• Active intraocular inflammation (e.g., uveitis)
• History of herpes simplex keratitis

• Respiratory: Timolol may cause bronchospasm or worsen asthma/COPD. Contraindicated in patients with severe pulmonary disease.
• Cardiovascular: May cause bradycardia, hypotension, and AV block. Monitor patients with cardiovascular disease.
• Iris Pigmentation: Latanoprost may cause gradual, permanent increase in brown pigmentation of the iris.
• Macular Edema: Especially in aphakic patients or those with posterior capsule rupture.
• Intraocular Inflammation: Use with caution in patients with uveitis or herpetic eye disease.
• Systemic Effects: Systemic absorption of timolol may cause fatigue, depression, or mask signs of hypoglycemia.
• Contact Lenses: Contains benzalkonium chloride, which may be absorbed by soft lenses.

Common (≥1%):

• Ocular: Eye irritation, conjunctival hyperemia, eyelash changes, blurred vision, dry eye, foreign body sensation
• Systemic: Headache, fatigue, dizziness, cold extremities

Less Common (<1%):

• Ocular: Iris pigmentation changes, photophobia, keratitis
• Systemic: Bradycardia, hypotension, depression

Serious (Rare):

• Bronchospasm
• Worsening of heart failure
• Macular edema
• Uveitis
• Herpes keratitis recurrence

Severity and Onset:

• Iris pigmentation changes are gradual and usually permanent.
• Systemic effects from timolol may occur, particularly in susceptible individuals.
• Most ocular side effects are mild and transient.

• Systemic Beta-Blockers: Additive effects may cause bradycardia or hypotension.
• Calcium Channel Blockers: Increased risk of AV block or hypotension.
• Digitalis Glycosides: Risk of bradycardia.
• Insulin and Oral Antidiabetics: Timolol may mask hypoglycemia symptoms.
• Clonidine: Abrupt withdrawal during timolol use may cause rebound hypertension.
• CYP2D6 Inhibitors (e.g., quinidine, fluoxetine): May increase systemic timolol levels.
• Other Ophthalmic Prostaglandin Analogs: Avoid concurrent use due to reduced efficacy and increased risk of adverse effects.

• International Guidelines (e.g., AAO, NICE): Recommend fixed-dose combinations like latanoprost + timolol for patients not controlled on monotherapy.
• Safety Monitoring: Emphasis on pre-treatment screening for respiratory and cardiovascular conditions due to timolol’s systemic absorption.
• Preservative-Free Options: Newer formulations aim to reduce preservative-related ocular surface toxicity.
• Improved Adherence: Fixed combinations improve compliance and reduce preservative load compared to multiple separate eye drops.

• Unopened Bottle: Store at 2°C to 8°C (refrigerated). Protect from light.
• After Opening: Store at room temperature up to 25°C. Discard after 6 weeks of opening.
• Handling Precautions:
• Do not freeze.
• Keep the bottle tightly closed.
• Avoid contact of dropper tip with any surface to prevent contamination.