LATIM EYE DROPS (Each bottle contains latanoprost/ Timolel maleate

Indications

• Raised intraocular pressure in open-angle glaucoma
• Ocular hypertension

Dosage

Children: Child: Apply once daily, to be administered preferably in the evening.

Adults: Apply once daily, preferably in the evening.

Mechanism of action

Latanoprost selectively stimulates the prostaglandin F2 alpha receptor, leading to increased outflow of aqueous humor. This mechanism involves remodeling the extracellular matrix and regulating matrix metalloproteinases, which enhances tissue permeability and modifies outflow resistance, thus decreasing intraocular pressure (IOP).

Pharmacodynamics

Latanoprost effectively reduces intraocular pressure by enhancing uveoscleral outflow. The onset of action occurs within 3 to 4 hours, reaching its maximum effect at 8 to 12 hours post-administration, with activity maintained for approximately 24 hours. Notably, long-term use may cause changes in iris pigmentation and other ocular effects such as conjunctival hyperemia and eyelash changes in a small proportion of patients.

Pharmacokinetics

Latanoprost is administered as eye drops and is absorbed through the cornea. It undergoes hydrolysis to its active form, which then exerts its therapeutic effects. The drug's effects are most pronounced within the first 12 hours after administration, with a duration of action that supports once-daily dosing. It is important to note that the presence of benzalkonium chloride in some formulations may cause ocular irritation.

Contra-indications

• Active herpes simplex keratitis
• History of recurrent herpetic keratitis associated with prostaglandin analogues

Adverse effects

• Iris pigmentation
• Conjunctival hyperemia
• Pigmentation of periocular tissues
• Eyelash changes
• Hypertrichosis
• Ocular irritation
• Dizziness
• Headache
• Myalgia
• Chest pain
• Dyspnoea
• Unstable angina

Interactions

• May interact with thiomersal-containing preparations
• Use with caution in patients receiving other ocular medications

Precautions

• Do not use within 5 minutes of thiomersal-containing preparations
• Monitor patients with a history of significant asthma
• Use with caution in patients with angle-closure glaucoma or aphakia
• Consider risks for uveitis in predisposed individuals

Pregnancy

Manufacturer advises to avoid use during pregnancy due to potential effects.

Breast-feeding

May be present in breast milk; manufacturer advises caution.

Storage

Store at room temperature. Protect from light. Once opened, use within a specified time frame as indicated by the manufacturer.

Formulations

• Latanoprost 50 microgram per 1 ml eye drops
• Monopost 50 micrograms/ml eye drops
• Medizol 50 micrograms/ml eye drops
• Xalatan 50 micrograms/ml eye drops

Indications

• Glaucoma
• Ocular hypertension
• Hypertension
• Angina pectoris
• Cardiac arrhythmias

Dosage

Children: Refer to the BNF for Children for appropriate dosing information.

Adults: Refer to the BNF for specific dosing guidelines as it varies based on condition and formulation.

Mechanism of action

Timolol works by blocking beta-adrenergic receptors in the eye, leading to a decrease in aqueous humor production. The reduction in aqueous humor decreases intraocular pressure. In systemic administration, timolol reduces heart rate and myocardial contractility by blocking beta-1 receptors in the heart and causes bronchodilation through beta-2 receptor blocking.

Pharmacodynamics

Timolol exhibits dose-dependent effects on heart rate and contractility. It decreases heart rate and cardiac output, leading to reduced oxygen demand by the heart. In the ocular system, it reduces intraocular pressure effectively by inhibiting the formation of aqueous humor, which is crucial in managing conditions like glaucoma.

Pharmacokinetics

Timolol is rapidly absorbed after administration, with peak plasma concentrations occurring within 1 to 3 hours. It has a half-life of approximately 4 to 5 hours. Timolol is extensively metabolized in the liver, and its excretion primarily occurs through the kidneys. The drug's systemic absorption can lead to significant cardiovascular effects, particularly in patients with pre-existing heart conditions.

Contra-indications

• Severe asthma or chronic obstructive pulmonary disease (COPD)
• Bradycardia
• Heart block greater than first degree
• Cardiogenic shock
• Hypersensitivity to timolol or any component of the formulation

Adverse effects

• Ocular discomfort
• Eye burning or stinging
• Headache
• Fatigue
• Dizziness
• Bradycardia
• Hypotension
• Respiratory distress in patients with asthma
• Systemic absorption leading to cardiovascular effects

Interactions

• Other antihypertensives may have additive effects leading to hypotension
• Calcium channel blockers can exacerbate bradycardia and hypotension
• Non-steroidal anti-inflammatory drugs (NSAIDs) may reduce the hypotensive effect
• Antidiabetic medications may mask signs of hypoglycemia

Precautions

• Use with caution in patients with a history of respiratory disease
• Monitor heart rate and blood pressure regularly
• Caution in patients with diabetes, as timolol may mask symptoms of hypoglycemia
• Caution in patients with thyroid disorders, as beta-blockers may mask signs of hyperthyroidism

Pregnancy

Timolol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Data on its safety in pregnancy are limited.

Breast-feeding

Timolol is excreted in breast milk, and caution should be exercised when administered to a nursing mother.

Storage

Store at room temperature, away from light and moisture. Do not freeze.

Formulations

• Ophthalmic solution (0.25%, 0.5%)
• Oral tablet (various strengths)

Mechanism of action

Elevated intraocular pressure leads to an increased risk of glaucomatous visual field loss. The higher the intraocular pressure, the higher the risk of damage to the optic nerve and loss of visual field. Latanoprost selectively stimulates the prostaglandin F2 alpha receptor and this results in a decreased intraocular pressure (IOP) via the increased outflow of aqueous humor, which is often implicated in cases of elevated intraocular pressure. Possible specific mechanisms of the abovementioned increased aqueous outflow are the remodeling of the extracellular matrix and regulation of matrix metalloproteinases. These actions result in higher tissue permeability related to humor outflow pathways, which likely change outflow resistance and/or outflow rates.

Pharmacodynamics

Latanoprost effectively decreases intraocular pressure by increasing uveoscleral outflow. A decrease in intraocular pressure has been measured within 3–4 hours post-administration, reaches a maximum decrease at 8–12 hours, and can be maintained for a period of 24 hours. **A note on eye and periorbital changes** Between 3 to 10% of patients taking latanoprost have experienced iris pigmentation after about 3-4 months of latanoprost use. Patients should be notified of this risk before initiating treatment. It may occur in both patients with light-colored irides (green-brown or blue/grey-brown) or dark-colored (brown) irides, but is less pronounced in the latter group. This drug may also cause other ocular effects including infrequent conjunctival hyperemia, pigmentation of periocular tissues, eyelash changes, hypertrichosis, and ocular irritation.