Latanoprost + Timolol

Usage

• Latanoprost + Timolol is prescribed for the reduction of intraocular pressure (IOP) in patients with open-angle glaucoma and ocular hypertension who are insufficiently responsive to topical beta-blockers or prostaglandin analogs alone.
• Pharmacological Classification: Antiglaucoma agent (combination of a prostaglandin analog and a beta-blocker).
• Mechanism of Action: Latanoprost increases uveoscleral outflow of aqueous humor, while Timolol decreases aqueous humor production. The combination results in a synergistic effect, lowering IOP more effectively than either drug alone.

Alternate Names

• Latanoprost/Timolol
• Brand Names: Xalacom, Xalcom.

How It Works

• Pharmacodynamics: Latanoprost, a prostaglandin F2α analog, is a selective prostanoid FP receptor agonist. Timolol is a non-selective beta-adrenergic receptor antagonist.
• Pharmacokinetics:
  • Absorption: Latanoprost is absorbed through the cornea, and Timolol is partially absorbed systemically.
  • Metabolism: Latanoprost is primarily metabolized in the liver via fatty acid beta-oxidation. Timolol is extensively metabolized in the liver.
  • Elimination: Both drugs are primarily eliminated in the urine, as metabolites, with some unchanged Timolol also present in the urine. The elimination half-life of Latanoprost acid is approximately 17 minutes, and for Timolol, approximately 6 hours.
• Mode of Action: Latanoprost increases uveoscleral outflow, reducing intraocular pressure. Timolol decreases aqueous humor production by the ciliary epithelium, further reducing IOP. The two mechanisms together have an additive effect, achieving a substantial decrease in IOP.
• Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Latanoprost is a prostanoid FP receptor agonist. Timolol is a non-selective beta-adrenergic receptor antagonist.

Dosage

Standard Dosage

Adults:

• One drop in the affected eye(s) once daily, usually in the morning.

Children:

• Not recommended for use in children under 18 years of age. Safety and efficacy have not been established.

Special Cases:

• Elderly Patients: Same as adult dosing.
• Patients with Renal Impairment: Use with caution. Close monitoring is recommended.
• Patients with Hepatic Dysfunction: Use with caution. Close monitoring is recommended.
• Patients with Comorbid Conditions: Use with caution in patients with asthma, COPD, cardiovascular disease, diabetes, or hyperthyroidism.

Clinical Use Cases

Latanoprost + Timolol is specifically indicated for chronic open-angle glaucoma and ocular hypertension, and not typically used in acute situations requiring rapid IOP reduction such as intubation, surgical procedures, or mechanical ventilation. For such situations, alternative IOP-lowering interventions (such as systemic medications) might be more appropriate.

Dosage Adjustments

• Dose adjustments might be required based on patient response and tolerance. However, the maximum recommended dosage is one drop daily in the affected eye(s). It should not be administered more frequently than once daily. Close monitoring of IOP is advisable in patients with hepatic/renal impairment.

Side Effects

Common Side Effects

• Blurred vision (transient)
• Eye irritation (burning, stinging, itching)
• Foreign body sensation
• Increased brown pigmentation of the iris
• Changes in eyelashes (increased length, thickness, darkening)

Rare but Serious Side Effects

• Bradycardia
• Hypotension
• Bronchospasm (especially in patients with asthma or COPD)
• Heart failure (exacerbation)
• Macular edema
• Iritis
• Uveitis

Long-Term Effects

• Permanent change in eye color (increased brown pigmentation of the iris).

Adverse Drug Reactions (ADR)

• Anaphylaxis (rare)
• Exacerbation of pre-existing respiratory or cardiac conditions

Contraindications

• Hypersensitivity to latanoprost, timolol, or any component of the formulation.
• Reactive airway disease (asthma, COPD).
• Sinus bradycardia, sick sinus syndrome, second- or third-degree atrioventricular block, overt cardiac failure, cardiogenic shock.

Drug Interactions

• Other beta-blockers (systemic and ophthalmic): Additive effects, increased risk of bradycardia and hypotension.
• Calcium channel blockers (oral): Increased risk of bradycardia and hypotension.
• Antiarrhythmics (e.g., amiodarone): Increased risk of bradycardia.
• Digitalis glycosides: Increased risk of bradycardia.
• CYP2D6 inhibitors (e.g., quinidine, fluoxetine, paroxetine): Potentiated systemic beta-blockade.
• Clonidine: Risk of hypertensive reaction upon clonidine withdrawal.
• Antidiabetic agents: Increased risk of hypoglycemia.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: C (Latanoprost), Xalacom is contraindicated in pregnancy.
• Latanoprost and Timolol may cross the placenta, presenting potential risks to the fetus.
• Both drugs are excreted in breast milk, posing risks to nursing infants. It’s advisable to discontinue breastfeeding or the drug during lactation depending on the clinical needs of the mother.

Drug Profile Summary

• Mechanism of Action: Latanoprost increases uveoscleral outflow; Timolol decreases aqueous humor production.
• Side Effects: Blurred vision, eye irritation, iris pigmentation changes, eyelash changes, bradycardia, hypotension, bronchospasm.
• Contraindications: Respiratory and cardiac conditions, hypersensitivity.
• Drug Interactions: Beta-blockers, calcium channel blockers, antiarrhythmics, digitalis.
• Pregnancy & Breastfeeding: Contraindicated in pregnancy; not recommended during breastfeeding.
• Dosage: One drop in affected eye(s) once daily.
• Monitoring Parameters: IOP, iris color, eyelashes, heart rate, blood pressure, respiratory function.

Popular Combinations

Latanoprost + Timolol is itself a popular combination. Combining it with other antiglaucoma agents may be considered on case to case basis if adequate IOP lowering is not achieved.

Precautions

• General Precautions: Evaluate patients for pre-existing respiratory and cardiovascular conditions. Monitor for side effects, particularly systemic beta-blocker effects.
• Specific Populations: Use cautiously in pregnant or lactating mothers, elderly individuals, and children under 18. Not for pregnant women due to potential fetal harm.
• Lifestyle Considerations: Transient blurred vision may affect driving and operating machinery.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Latanoprost + Timolol?

A: One drop in the affected eye(s) once daily.

Q2: Can Latanoprost + Timolol be used in children?

A: Not recommended for use in children under 18, as safety and efficacy haven’t been established.

Q3: What are the most common side effects?

A: Blurred vision, eye irritation, increased brown pigmentation of the iris, and changes to the eyelashes.

Q4: What are the contraindications to using Latanoprost + Timolol?

A: Asthma, COPD, certain heart conditions (bradycardia, heart block, heart failure), and hypersensitivity to the drug’s components.

Q5: Can Latanoprost + Timolol be used during pregnancy or breastfeeding?

A: Contraindicated in pregnancy and not recommended while breastfeeding.

Q6: How does Latanoprost + Timolol interact with other medications?

A: May interact with other beta-blockers, calcium channel blockers, and certain heart medications. Provide a complete list of current medications to your physician.

Q7: What should patients be advised regarding contact lens use?

A: Remove contact lenses before instilling the drops and wait at least 15 minutes before reinserting them.

Q8: Can Latanoprost + Timolol worsen pre-existing respiratory problems?

A: Yes, especially in patients with asthma or COPD. Use with caution in these individuals.

Q9. How long does it take for Latanoprost + Timolol to lower IOP?

A: Onset of action is typically within one hour, with maximum IOP reduction within 3-4 hours (latanoprost) and 30 minutes (timolol). Duration of effect lasts up to 24 hours.