Adult: Available preparation:
Latanoprost 50 mcg and timolol 5 mg per mL of eye drop solution
In patients who do not adequately respond to topical β-blockers or prostaglandin analogues: Instil 1 drop into the affected eye(s) once daily.
Incompatibility
Latanoprost: May form precipitate with thiomersal-containing eye drops.
Contraindications
Reactive airway disease (e.g. existing or history of bronchial asthma, severe COPD); sinus bradycardia, sick sinus syndrome, sino-atrial block, 2nd- or 3rd-degree atrioventricular block (not controlled with a pacemaker), overt cardiac failure, cardiogenic shock; active herpes simplex keratitis or history of recurrent herpetic keratitis specifically associated with prostaglandin analogues.
Special Precautions
Patients with history of atopy or severe anaphylaxis to allergens, 1st-degree heart block, heart failure, orthostatic hypotension, severe peripheral circulatory disturbance or disorders (e.g. severe forms of Raynaud’s syndrome), mild or moderate COPD, diabetes (especially labile diabetes), hyperthyroidism, corneal diseases, other types of glaucoma (e.g. inflammatory, neovascular or chronic angle-closure glaucoma, open-angle glaucoma of pseudophakic patients, pigmentary glaucoma), closed-angle glaucoma (as monotherapy), history of herpetic keratitis, active intraocular inflammation; aphakic patients, pseudophakic patients with torn posterior lens capsule, risk factors for macular oedema; myasthenia gravis. Patients undergoing surgery.
Adverse Reactions
Significant: Choroidal detachment (post-filtration procedures), increased iris pigmentation, eyelid skin and eyelash changes (increased length, darkening and thickening of the eyelashes), anaphylactic reactions, bacterial keratitis, macular oedema (e.g. cystoid macular oedema). Eye disorders: Eye pain or irritation (e.g. stinging, burning, itching, foreign body sensation), blepharitis, blurred vision, corneal disorder, conjunctivitis, eye hyperaemia. Nervous system disorders: Dizziness, headache. Skin and subcutaneous tissue disorders: Rash. Potentially Fatal: Cardiac failure; bronchospasm (in patients with asthma).
Patient Counseling Information
Remove contact lenses before administration and reinsert after 15 minutes. This drug may cause transient blurring of vision, if affected, do not drive or operate machinery.
Monitoring Parameters
Monitor intraocular pressure, changes in iris colour and eyelash; systemic effects of β blockade; signs and symptoms of heart failure.
Overdosage
Symptoms: Latanoprost: Ocular irritation and conjunctival hyperaemia.
Timolol (systemic): Bradycardia, hypotension, bronchospasm and cardiac arrest.
Management: Symptomatic and supportive treatment.
Drug Interactions
May have potentiated effects on intraocular pressure or systemic β-blockade with oral or other topical β-adrenergic blockers.
Latanoprost: Paradoxical increase in intraocular pressure with another prostaglandin analogues.
Timolol: May have additive effects resulting in hypotension and/or notable bradycardia with oral Ca channel blockers, guanethidine, antiarrhythmics (e.g. amiodarone), digitalis glycosides, parasympathomimetics, narcotics and MAOIs. Potentiated systemic β blockade (e.g. decreased heart rate, depression) with CYP2D6 inhibitors (e.g. quinidine, fluoxetine, paroxetine). May result in mydriasis with epinephrine. May potentiate the hypertensive reaction to sudden withdrawal of clonidine. May increase the hypoglycaemic effect of anti-diabetic agents.
Action
Description: Latanoprost, a prostaglandin F2α analogue, is a selective prostanoid FP receptor agonist which reduces IOP by primarily increasing the uveoscleral outflow of the aqueous humour.
Timolol, a non-selective adrenergic receptor antagonist, reduces IOP by decreasing the production of aqueous humour in the ciliary epithelium. Onset: Within 1 hour.
Latanoprost: Intraocular pressure reduction: 3-4 hours.
Timolol: Intraocular pressure reduction: 30 minutes. Duration: Up to 24 hours.
Timolol: 24 hours. Pharmacokinetics: Absorption: Latanoprost: Well-absorbed through the cornea. Bioavailability: 45% (acid of latanoprost). Time to reach maximum concentration in the aqueous humour: 2 hours.
Timolol: Partly absorbed systemically. Time to reach maximum concentration in the aqueous humour: Approx 1 hour. Time to peak plasma concentration: 10-20 minutes. Distribution: Latanoprost: Volume of distribution: Approx 0.16 L/kg (acid of latanoprost). Plasma protein binding: 87%.
Timolol: Enters breast milk. Metabolism: Latanoprost: Primarily metabolised in the liver via fatty acid beta-oxidation.
Timolol: Extensively metabolised in the liver. Excretion: Latanoprost: Mainly via urine (as metabolites). Elimination half-life: 17 minutes (acid of latanoprost).
Timolol: Via urine (as metabolites with some unchanged drug). Elimination half-life: Approx 6 hours.
Chemical Structure
Latanoprost Source: National Center for Biotechnology Information. PubChem Database. Latanoprost, CID=5311221, https://pubchem.ncbi.nlm.nih.gov/compound/Latanoprost (accessed on Jan. 22, 2020)
Timolol Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 33624, Timolol. https://pubchem.ncbi.nlm.nih.gov/compound/33624. Accessed July 26, 2022.
Storage
Store between 2-8°C. Opened bottle: Store below 25°C; use within 4 weeks. Protect from light.
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