Prostaglandin analogs Ophthalmology

• Bimatoprost 0.01%, 0.03% (Lumigan®)
• Latanoprostene bunod 0.024% (Vyzulta™)
• Latanoprost 0.005% (Xalatan®)
• Latanoprost ophthalmic emulsion 0.005% (Xelpros™)
• Tafluprost ophthalmic solution 0.0015% (PF) (Zioptan™)
• Travoprost 0.004% (Travatan® Z)

Latanoprost 0.005% (Xalatan®)

Latanoprost 0.005% (Xalatan®) 

Pharmacology:   Latanoprost is a prostanoid selective FP receptor agonist that is believed to reduce the intraocular pressure (IOP) by increasing the outflow of aqueous humor. Studies in animals and man suggest that the main mechanism of action is increased uveoscleral outflow.   Reduction of the IOP in man starts about 3–4 hours after administration and maximum effect is reached after 8–12 hours. IOP reduction is present for at least 24 hours.   The elimination of the acid of latanoprost from human plasma is rapid (t 1/2 = 17 min). 

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

Side effects: Most common adverse reactions (≥4%) from clinical trials are blurred vision, burning and stinging, conjunctival hyperemia, foreign body sensation, itching, increased pigmentation of the iris, punctate keratitis, and upper respiratory tract infection/nasopharyngitis/influenza.

Efficacy: Patients with mean baseline IOP of 24 – 25 mmHg who were treated for 6 months in multi-center, randomized, controlled trials demonstrated 6 – 8 mmHg reductions in IOP. This IOP reduction with Latanoprost Ophthalmic Solution 0.005% dosed once daily was equivalent to the effect of timolol 0.5% dosed twice daily.

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Tafluprost ophthalmic solution 0.0015% (PF) (Zioptan™):

Tafluprost ophthalmic solution 0.0015% (PF) (Zioptan™) 

Pharmacology:  Tafluprost acid, a prostaglandin analog is a selective FP prostanoid receptor agonist which is believed to reduce intraocular pressure by increasing uveoscleral outflow. Tafluprost, an ester prodrug, is hydrolyzed to its biologically active acid metabolite in the eye. The acid metabolite is further metabolized via fatty acid β‑oxidation and phase II conjugation.

Dosing: One drop in the affected eye(s) once daily in the evening.  Advise patients that ZIOPTAN® is a sterile solution that does not contain a preservative. The solution from one individual unit is to be used immediately after opening for administration to one or both eyes. Since sterility cannot be maintained after the individual unit is opened, the remaining contents should be discarded immediately after administration.

Side effects: Ocular adverse reactions reported at an incidence of ≥2% in these clinical studies included ocular stinging/irritation (7%), ocular pruritus including allergic conjunctivitis (5%), cataract (3%), dry eye (3%), ocular pain (3%), eyelash darkening (2%), growth of eyelashes (2%) and vision blurred (2%).

Efficacy: In clinical studies up to 24 months in duration, patients with open-angle glaucoma or ocular hypertension and baseline pressure of 23 to 26 mm Hg who were treated with ZIOPTAN® dosed once daily in the evening demonstrated reductions in intraocular pressure at 3 and 6 months of 6 to 8 mmHg and 5 to 8 mmHg, respectively.

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Bimatoprost 0.01%, 0.03% (Lumigan®):

Bimatoprost 0.01%, 0.03% (Lumigan®) 

Pharmacology:   Bimatoprost, a prostaglandin analog, is a synthetic structural analog of prostaglandin with ocular hypotensive activity. It selectively mimics the effects of naturally occurring substances, prostamides. Bimatoprost is believed to lower intraocular pressure (IOP) in humans by increasing outflow of aqueous humor through both the trabecular meshwork and uveoscleral routes. Elevated IOP presents a major risk factor for glaucomatous field loss. The higher the level of IOP, the greater the likelihood of optic nerve damage and visual field loss. Elimination half-life of approximately 45 minutes.

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

Side effects: In clinical trials, the most frequent events associated with the use of bimatoprost ophthalmic solution, 0.03% occurring in approximately 15% to 45% of patients, in descending order of incidence, included conjunctival hyperemia, growth of eyelashes, and ocular pruritus. Approximately 3% of patients discontinued therapy due to conjunctival hyperemia.

In a 12-month clinical study with bimatoprost ophthalmic solutions 0.01%, the most common adverse reaction was conjunctival hyperemia (31%). Approximately 1.6% of patients discontinued therapy due to conjunctival hyperemia. Other adverse drug reactions (reported in 1 to 4% of patients) with LUMIGAN® 0.01% in this study included conjunctival edema, conjunctival hemorrhage, eye irritation, eye pain, eye pruritus, erythema of eyelid, eyelids pruritus, growth of eyelashes, hypertrichosis, instillation site irritation, punctate keratitis, skin hyperpigmentation, vision blurred, and visual acuity reduced.

Efficacy:In a 12-month clinical study of patients with open angle glaucoma or ocular hypertension with an average baseline IOP of 23.5 mmHg, the IOP-lowering effect of LUMIGAN® 0.01% once daily (in the evening) was up to 7.5 mmHg.

In clinical studies of patients with open angle glaucoma or ocular hypertension with a mean baseline IOP of 26 mmHg, the IOP-lowering effect of bimatoprost ophthalmic solution, 0.03% once daily (in the evening) was 7 to 8 mmHg.

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Latanoprostene bunod 0.024% (Vyzulta™):

Latanoprostene bunod 0.024% (Vyzulta™) 

Pharmacology:  Latanoprostene bunod is thought to lower intraocular pressure by increasing outflow of aqueous humor through both the trabecular meshwork and uveoscleral routes. Reduction of the intraocular pressure starts approximately 1 to 3 hours after the first administration with the maximum effect reached after 11-13 hours in eyes with elevated intraocular pressure.

After topical ocular administration, latanoprostene bunod is rapidly metabolized in the eye to latanoprost acid (active moiety), an F2α prostaglandin analog, and butanediol mononitrate. Butanediol mononitrate is metabolized to 1,4-butanediol and nitric oxide
which has an effect on the trabecular meshwork and Schlemm’s canal leading to enhanced aqueous outflow.

The elimination of latanoprost acid from human plasma is rapid as latanoprost acid plasma concentration dropped below the LLOQ (30 pg/mL) in the majority of subjects by 15 minutes following ocular administration of VYZULTA 0.024% in humans.

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

Side effects: VYZULTA was evaluated in 811 patients in 2 controlled clinical trials of up to 12 months duration. The most common ocular adverse reactions observed in patients treated with latanoprostene bunod were: conjunctival hyperemia (6%), eye irritation (4%), eye pain (3%), and instillation site pain (2%).

Efficacy: In clinical studies up to 12 months duration, patients with open-angle glaucoma or ocular hypertension with average baseline intraocular pressures (IOPs) of 26.7 mmHg, the IOP-lowering effect of VYZULTA (latanoprostene bunod ophthalmic solution) 0.024% once daily (in the evening) was up to 7 to 9 mmHg.

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Travoprost 0.004% (Travatan® Z):

Travoprost 0.004% (Travatan® Z) 

Pharmacology:  Reduction of the IOP starts approximately 2 hours after the first administration with maximum effect reached after 12 hours.

Travoprost free acid, a prostaglandin analog is a selective FP prostanoid receptor agonist, which is believed to reduce IOP by increasing uveoscleral outflow. The terminal elimination half-life of travoprost free acid was estimated from fourteen subjects and ranged from 17 minutes to 86 minutes with the mean half-life of 45 minutes.

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

Side effects: The most common adverse reaction observed in controlled clinical trials with TRAVATAN and TRAVATAN Z was ocular hyperemia, which was reported in 30% to 50% of patients. Up to 3% of patients discontinued therapy due to conjunctival hyperemia. Ocular adverse reactions reported at an incidence of 5% to 10% in these clinical trials included decreased visual acuity, eye discomfort, foreign body sensation, pain, and pruritus.

Ocular adverse reactions reported at an incidence of 1% to 4% in clinical trials with TRAVATAN or TRAVATAN Z included abnormal vision, blepharitis, blurred vision, cataract, conjunctivitis, corneal staining, dry eye, iris discoloration, keratitis, lid margin crusting, ocular inflammation, photophobia, subconjunctival hemorrhage, and tearing.

While significantly less toxic than BAK, sofZia® still causes some negative effects and, interestingly, clinical trials have not demonstrated much difference in patient comfort when compared to BAK.

TRAVATAN Z contains Active: travoprost 0.04 mg/mL; Inactives: polyoxyl 40 hydrogenated castor oil, sofZia® (boric acid, propylene glycol, sorbitol, zinc chloride), sodium hydroxide and/or hydrochloric acid (to adjust pH), and purified water, USP. Preserved in the bottle with an ionic buffered system, sofZia® (BAK-Free).

Efficacy: In clinical studies, patients with open-angle glaucoma or ocular hypertension and baseline pressure of 25 to 27 mmHg, who were treated with TRAVATAN or TRAVATAN Z dosed once daily in the evening, demonstrated 7 to 8 mmHg reductions in IOP. In sub-group analyses of these studies, mean IOP reduction in black patients was up to 1.8 mmHg greater than in non-black patients. It is not known at this time whether this difference is attributed to race or to heavily pigmented irides.

In a multi-center, randomized, controlled trial, patients with mean baseline IOP of 24 to 26 mmHg on TIMOPTIC** 0.5% twice daily who were treated with TRAVATAN dosed daily adjunctively to TIMOPTIC** 0.5% twice daily demonstrated 6 to 7 mmHg reductions in IOP.

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Latanoprost ophthalmic emulsion 0.005% (Xelpros™):

Latanoprost ophthalmic emulsion 0.005% (Xelpros™) 

Pharmacology:  Latanoprost is a prostaglandin F2α analogue that is believed to reduce the intraocular pressure (IOP) by increasing the outflow of aqueous humor. Reduction of the IOP in man starts about 3-4 hours after administration and maximum effect is reached after 8-12 hours. IOP reduction is present for at least 24 hours. The elimination of the acid of latanoprost from human plasma is rapid (t1/2 =17 min)

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

Side effects: Across multiple clinical trials conducted with XELPROS (latanoprost ophthalmic emulsion) 0.005%, the most frequently reported ocular adverse reactions were eye pain/stinging upon instillation and ocular hyperemia, reported in 55% and 41% of XELPROS treated patients, respectively. Less than 1% of patients discontinued therapy because of intolerance to the eye pain/stinging or to the ocular hyperemia.

Efficacy: In randomized, controlled clinical trials of patients with open angle glaucoma or ocular hypertension with mean baseline IOP of 23 - 26 mmHg, the mean IOP-lowering effect of XELPROS administered once daily in the evening was up to 6 - 8 mmHg.

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