LATIM EYE DROPS (EACH BOTTLE CONTAINS LATANOPROST/TIMOLOLMALAEATE-0.005%W/V 0.5%W/V

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
• Heart failure

Dosage

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

Adults: Refer to specific guidelines or the BNF for appropriate dosing information.

Mechanism of action

Timolol maleate acts by blocking beta-adrenergic receptors (both beta-1 and beta-2) in various tissues, particularly in the eye. This blockade leads to a reduction in the secretion of aqueous humor by the ciliary body, resulting in decreased intraocular pressure. The systemic effects include reduced heart rate and myocardial contractility, which contributes to its antihypertensive properties.

Pharmacodynamics

Timolol exhibits dose-dependent inhibition of beta-adrenergic receptor activity, leading to its therapeutic effects. The decrease in heart rate and contractility reduces cardiac output and lowers blood pressure. In the eye, the reduction in aqueous humor production results in lower intraocular pressure, making it effective in the treatment of glaucoma. The onset of action for topical administration in the eye is typically within 30 minutes, with peak effects occurring around 1 to 2 hours after application.

Pharmacokinetics

Timolol is well absorbed from the gastrointestinal tract and ocular surface, with significant first-pass metabolism occurring in the liver. The systemic half-life of timolol is approximately 4 to 6 hours, although its effects may last longer due to prolonged action in ocular tissues. It is excreted primarily through the kidneys. The bioavailability of timolol can be affected by factors such as age, liver function, and concurrent medications.

Contra-indications

• Asthma or severe 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 irritation
• Burning or stinging on instillation
• Dry eyes
• Blurred vision
• Systemic effects such as bradycardia, hypotension, fatigue, and depression

Interactions

• Concomitant use with other beta-blockers may enhance effects
• Caution with calcium channel blockers, as they may increase the risk of bradycardia and hypotension
• Caution with antidiabetic medications, as timolol may mask signs of hypoglycemia

Precautions

• Use with caution in patients with cardiovascular disease
• Monitor for signs of bronchospasm in patients with a history of respiratory disease
• Consider potential interactions with systemic beta-blockers

Pregnancy

Timolol should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus, as there is limited data on its safety.

Breast-feeding

Timolol is excreted in breast milk. Caution should be exercised when administering to a nursing mother.

Storage

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

Formulations

• Ophthalmic solution
• Ophthalmic gel forming solution

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.