TABLE 1.
Selected health authority-approved IOP-lowering agents and their properties.
| Brand name of drug & year of clinical Introduction/FDA or EMEA or Japan approval (where known) | Generic name & drug type. (IOP reduction achieved in OHT/POAG patients) | Dosage type (%, w/v) | Topical ocular dosing frequency | Mechanism of action to lower IOP | Some Side-Effects/Adverse reactions |
|---|---|---|---|---|---|
| Approved enhancers of conventional outflow (TM/SC pathway) of AQH to lower IOP | |||||
| Isopto carpine (1974); Pilopine | Pilocarpine (muscarinic receptor agonist) | 1, 2, 4%; 4% Gel | 1 drop 2-4-times daily; single application of gel across the eye | Enhances conventional (TM) outflow of AQH | Brow-ache, miosis; accommodative change, eye irritation, eye pain, blurred vision, and/or visual impairment, potential tachycardia |
| Isopto Carbachol | Carbachol (muscarinic receptor agonist) | 1.5, 3% solution | 1–2 drops up to 3-times daily | Enhances conventional (TM) outflow of AQH | Brow-ache, miosis, accommodative change, eye irritation, eye pain, blurred vision, and/or visual impairment, potential tachycardia |
| Glanatec (2014 Japan) | Ripasudil (Rho kinase [ROCK] inhibitor) (3.5–4.5 mmHg IOP reduction) | 0.4% solution | Enhances conventional (TM) outflow of AQH | Conjunctival hyperemia, allergic conjunctivitis, blepharitis, punctate keratitis | |
| Rhopressa (2017) | Netarsudil (Rho kinase [ROCK] inhibitor) (5 mmHg IOP reduction) | 0.02% solution | 1 drop daily | Enhances conventional (TM) outflow of AQH; also decreases episcleral veinous pressure | Conjunctival hyperemia, corneal verticillata, instillation site pain, and conjunctival hemorrhage |
| Approved Inhibitors of AQH Production to Lower IOP | |||||
| Timoptic (1978) Timoptic-XE Gel | Timolol (beta-adrenoceptor antagonist) | 0.25%, 0.5% solution or gel-forming solution | 1 drop 1-2-times daily | Reduces production of AQH from CB | Signs and symptoms of ocular irritation, (e.g. burning, stinging, itching, tearing, redness), conjunctivitis, blepharitis, keratitis, dry eyes, decreased corneal sensitivity, blurred vision, corneal erosion. Visual disturbance, including refractive changes |
| Betoptic (1985) | Betaxolol (beta-1-selective adrenoceptor antagonist) | 0.25% suspension; 0.5% solution | 1 drop 2-times daily; 1–2 drops twice daily | Reduces production of AQH from CB | Transient ocular discomfort, Decreased corneal sensitivity, erythema, itching sensation, corneal punctate keratitis, anisocoria, blurred vision, foreign body sensation, tearing, dryness of eyes, inflammation, discharge, ocular pain, decreased visual acuity, crusty lashes and photophobia; Bradycardia, heart block; Pulmonary distress characterized by dyspnoea, bronchospasm, thickened bronchial secretions, asthma and respiratory failure; Insomnia, dizziness, vertigo, headaches, depression, lethargy |
| Alphagan (1996) | Brimonidine (2–6 mmHg IOP reduction) | 0.15%, 0.2% solution | 1 drop 3-times daily | Reduces production of AQH from CB and enhances UVS AQH outflow | Allergic conjunctivitis, conjunctival hyperemia, and eye pruritis; local ocular hypersensitivity; blurred vision, burning sensation of eyes, drowsiness, eye headache, stinging of eyes, foreign body sensation |
| Iopidine (1987) | Apraclonidine | 0.5% solution | 1–2 drops 3-times daily | Reduces production of AQH from CB | Hyperemia (redness), itching, tearing of the eye, Blurred vision or change in vision, chest pain, clumsiness or unsteadiness, depression, dizziness, eye discharge, irritation, or pain, irregular heartbeat |
| Trusopt (1994) | Dorzolamide (carbonic anhydrase inhibitor | 2% solution | 1 drop 3-times daily | Reduces AQH generation by the CB | Transient bitter taste and superficial punctate keratitis, eye irritation, burning, stinging, and ocular discomfort; blurred vision, excessive tearing, dry eyes, and increased sensitivity to light |
| Azopt (1998) | Brinzolamide (carbonic anhydrase inhibitor | 1% suspension | 1 drop 3-times daily | Reduces AQH generation by the CB | Temporary blurred vision, bitter/sour/unusual taste, dry eyes, temporary discomfort, itching, redness of the eye, foreign body sensation, eye discharge, and headache |
| Approved Stimulators of UVS Outflow of AQH to Lower IOP | |||||
| Xalatan (1996) | Latanoprost (FP-prostaglandin receptor-selective agonist | 0.005% solution | 1 drop at bedtime | Enhances AQH outflow via the UVS pathway and some via TM/SC pathway | Blurred vision, burning, stinging, itching, hyperemia, foreign body sensation, changes in eyelash number/color/length/thickness, iridial darkening, (pigmentation), periocular skin darkening, deepening of eyelid sulcus (loss of periorbital fat), dry eye, eyelid crusting and discomfort, increased sensitivity to light |
| Travatan (2001) | Travoprost (FP-prostaglandin receptor-selective agonist | 0.004% solution | 1 drop at bedtime | Enhances AQH outflow via the UVS pathway and some via TM/SC pathway | Blurred vision, burning, stinging, itching, hyperemia, foreign body sensation, changes in eyelash number/color/length/thickness, iridial darkening, (pigmentation), periocular skin darkening, deepening of eyelid sulcus (loss of periorbital fat), dry eye, eyelid crusting and discomfort, increased sensitivity to light |
| Lumigan (2001) | Bimatoprost (FP-prostaglandin receptor-selective agonist | 0.03% solution | 1 drop at bedtime | Enhances AQH outflow via the UVS pathway and some via TM/SC pathway | Increased conjunctival hyperemia, darkening of eyelids, increased thickening and number of eyelashes, dry eye, eye irritation, eye itching |
| Hirsutism (a condition of hair growth on parts of the body normally without hair) | |||||
| Taflotan (2008 Japan) | Tafluprost (FP-prostaglandin receptor-selective agonist | 0.0015% solution | 1 drop at bedtime | Enhances AQH outflow via the UVS pathway and some via TM/SC pathway | Ocular surface burning, stinging, irritation, hyperemia, foreign body sensation, dry eyes, watering eyes, iridial darkening, periocular skin darkening, abnormal eyelash growth, and increased sensitivity to light |
| Zioptan (2012 United States) | |||||
| Rescula (2000) | Unoprostone (FP-prostaglandin receptor agonist | 0.15% solution | 1 drop twice daily | Enhances AQH outflow via the UVS pathway and some via TM/SC pathway | Eye burning, stinging, dry eyes, itching, increased length of eyelashes, and injection; iridial darkening, blepharitis, cataract, conjunctivitis, corneal lesion, discharge from the eye, eye hemorrhage, eye pain, keratitis, irritation, and photophobia |
| Eybelis (2018 Japan) | Omidenepag Isopropyl (EP2-receptor selective non-prostaglandin agonist | 0.002% solution | 1 drop daily | Enhances AQH outflow via the UVS pathway and via TM/SC pathway | Transient conjunctival hyperemia, corneal thickening |
| Some Approved Combination Products for Lowering IOP | |||||
| Cosopt (1998) | Dorzolamide + timolol | 2% + 0.5% | 1 drop 2-times daily | Reduce AQH production from CB | Combination of side-effects from both drugs |
| Combigan (2007) | Brimonidine + timolol | 0.2% + 0.5% | 1 drop every 12 h | Reduce AQH production from CB | Combination of side-effects from both drugs |
| Simbrinza (2013) | Brinzolamide + Brimonidine | 1% + 0.2% | 1 drop 3-times daily | Reduce AQH production from CB | Combination of side-effects from both drugs |
| Roclatan (2019) | Netarsudil + Latanoprost | 0.02% + 0.005% | 1 drop daily | Enhancement of AQH outflow via TM/SC and UVS pathways | Combination of side-effects from both drugs |
| Xalacom | Latanoprost + timolol | 0.005% + 0.5% | 1 drop daily | Enhancement of AQH outflow and by inhibiting AQH production | Combination of side-effects from both drugs |
| Duotrav | Travoprost + timolol | 0.004% + 0.5% | 1 drop daily | Enhancement of AQH outflow and by inhibiting AQH production | Combination of side-effects from both drugs |
| Ganfort | Bimatoprost + timolol | 0.03% + 0.5% | 1 drop daily | Enhancement of AQH outflow and by inhibiting AQH production | Combination of side-effects from both drugs |
| Taflotan + timolol | Taflotan + timolol (>13 mmHg IOP reduction; 40% lowering) | 0.0015% + 0.5% | 1 drop daily | Enhancement of AQH outflow and by inhibiting AQH production | Combination of side-effects from both drugs |
| Other Products for Lowering IOP | |||||
| Vyzulta (2017) | Latanoprostene Bunod (conjugate of latanoprost and an NO-donor agent) | 0.024% solution | 1 drop at bedtime | Enhances AQH outflow via the UVS pathway and via TM/SC pathway | Eye discomfort/irritation, hyperemia, temporary blurred vision, increase in eyelash number/length/thickness and darkening of the eyelashes/eyelids and iris |
| Durysta Implant (2020) | Intracamerally injected sustained-delivery biodegradable polymer containing bimatoprost | Not applicable | Once implanted into the ANC of the eye (intracameral injection), the drug elutes off the implant over 6-months | Enhances AQH outflow via the UVS pathway and via TM/SC pathway | Conjunctival hyperemia, foreign body sensation, eye pain, photophobia, conjunctival hemorrhage dry eye, eye irritation increased IOP, corneal endothelial cell loss, vision blurred, iritis, headache |