Medication Review: Prostaglandin Analogs for Glaucoma

Glaucoma is one of the leading causes of blindness, often due to elevated intraocular pressure (IOP). Elevated IOP can lead to damage of the optic nerve, which can progress to irreversible vision loss.

In most cases, prostaglandin analog eye drops are considered first-line treatment for glaucoma. Currently, there are 4 different types available for this indication: bimatoprost, latanoprost, tafluprost, and travoprost.

All 4 of these medications are indicated for the reduction of IOP in patients with open-angle glaucoma or ocular hypertension. These medications work by increasing the drainage of aqueous outflow from the eye, which in turns lowers IOP.

The prostaglandin analogs can reduce IOP typically by 25% to 30%. Because the medications take about 2 weeks to achieve their maximum therapeutic effect, follow-up for efficacy should occur no sooner than 2 weeks.

The recommended dose for all 4 medications is 1 drop administered once a day in each eye. More frequent use of prostaglandin analogs has been shown to decrease the drugs’ IOP-lowering effect.¹

There is currently no indication for which these medications should be used together or dosed more than once per day. Therefore, a pharmacist should question the prescriber when a patient is on duplicate prostaglandin analog therapy, or if the dosing is more than 1 drop for each eye per day.

The manufacturer and package inserts recommend that these medications be administered in the evening. The optimal effects of latanoprost (Xalatan) have been seen when the medication is administered in the evening, versus in the morning.² Travoprost (Travatan) showed no difference when administered in the morning or evening; however, the package insert still recommends the dose to be given in the evening^3,4.

It is important for the patient to instill these drops daily without missing doses, as the benefits are greater when taking the medication every morning than taking the medication at night and missing doses. Overall, daily treatment adherence is more important than time of day of administration.

All prostaglandin analogs can be used with contact lenses.^1,4,5,6 However, contact lenses should be removed prior to instilling the medication. The lenses may be reinserted 15 minutes after administration of the eye drop.

Prostaglandin analogs may also be used in conjunction with other eye drops. The current recommendation is to separate drop administration by at least 5 minutes.^1,4,5,6

Side effects are similar across the 4 prostaglandin analogs. One common side effect is changes in eyelash and vellus hair (fine, barely noticeable hairs).

These changes include increase in length, thickness, pigmentation, and number. Rarely, fine hair can grow on the eyelid skin or corner of the eye.

Some eyelashes can grow so large that they turn in and rub on the cornea, causing irritation and a foreign body sensation. These effects appear to be reversible upon discontinuation of the treatment.^1,4,5,6

All prostaglandin analogs can cause the iris or eyelid to turn a darker color because of melanin deposits. The change in iris color tends to be permanent, even after the medication has been stopped, but the darkening of the eyelid skin tends to be reversible in some patients.^1,4,5,6

These color changes may not present for months or years. Brown pigmentation typically starts around the pupil and then spreads towards the periphery, though the long-term effect is unknown.

The extent of these side effects seems to be similar across the different types of prostaglandin analogs.

Typically in practice, the potential of color change to the iris is rarely a concern to patients. Most often, patients are more concerned about preserving their vision than cosmetic effects, though patients should still be warned of the potential adverse effect.

Another frequent side effect is red, irritated, or puffy eye appearance.^1,4,5,6 Travatan and bimatoprost (Lumigan) are more likely to cause side effects like redness, stinging, and hyperemia. Hyperemia is a side effect of the prostaglandin itself, and not necessarily the preservatives in the drops.

The prostaglandins analogs can also cause ocular inflammation. Generally, the medications should not be used in patients with active intraocular inflammation such as uveitis or iritis, because they can exacerbate the inflammation.^1,4,5,6

Other ocular side effects include foreign body sensation, ocular pruritus, decrease in vision, reactivation of uveitis, herpes infection of the cornea, bacterial keratitis, and swelling of the retina (macular edema). Non-ocular adverse reactions that have been reported include exacerbation of asthma, headache, common cold, cough, muscle/joint pain, and urinary tract infection (UTI).

Pharmacists should consult package inserts for a complete list of side effects per prostaglandin analog.^1,4,5,6

Here is a review of each prostaglandin analog:

Latanoprost (Xalatan)

Currently, this eye drops is the only prostaglandin analog available as a generic.

Because latanoprost breaks down more easily and becomes ineffective faster than the other 3 prostaglandin analogs, it is sold in 5-mL bottles that have only 2.5 mL of fluid.

Due to the instability of this medication, it is recommended the unopened bottle be kept in the refrigerator. Once opened, the bottle may be stored at room temperature for up to 6 weeks.¹

Brand-name Xalatan comes in a flatter, more flexible clear plastic bottle than some of the generic latanoprost drops, which often come in a round bottle with slightly stiffer plastic. This can make a difference if a patient has trouble operating the bottle.

Pfizer has developed Xal-Ease, a very patient friendly eye drop dispenser to be used with brand-name Xalatan that ensures 1 targeted drop with each squeeze of the trigger. This is a helpful option for a patient who may have problems administering the drops.

The use of Xal-Ease made it significantly less likely the subject would need help by someone in instilling drops (6.9% vs 18.1%, P<0.001). It also reduced the probability of the tip of the bottle touching the eye (3.2% vs 35.6%, p<0.001).⁷

The Xal-Ease device may not be compatible with generic latanoprost bottles,⁷ but there are other generic eye drop dispensers available, such as the Opticare eye drop dispenser and Autodrop eye drop guide. A patient would need to find one that is compatible with their bottle.

Latanoprost seems to exhibit greater ocular tolerability than the other prostaglandin analogs.⁸ The fact that this medication is well tolerated and available as a generic makes it most appealing to patients and prescribers.⁸

Travoprost (Travatan, Travatan Z)

A generic version of Travatan Z has been approved by the FDA, but at this time, only the brand-name version is commercially available.

Travoprost most closely mimics latanoprost. Travatan and Travatan Z are available in 2.5-mL solution in a 4-mL bottle and 5-mL solution in a 7.5-mL bottle.

Travatan Z is an updated solution replacing benzalkonium chloride, a known ocular irritant preservative, with Sofzia, an ionic buffered preservative that is gentler on the ocular surface. This is an option for those with ocular sensitivities.

It is not necessary to store Travatan eye drops in the refrigerator, but it is acceptable if the patient prefers the feel of cool drops on their eyes. Regardless, the medication should be stored in the cool place.

Like Xalatan and generic latanoprost, Travatan has a clear bottle that helps patients monitor their supply. It is important to explain to patients that their new bottles of eye drops will be half full on purpose. The manufacturer does this to help facilitate a drop-forming action of the liquid from the bottle.

Bimatoprost (Lumigan)

This eye drop is available as a more concentrated 0.03% solution. It does have the greatest tendency of the 4 prostaglandin analogs to cause conjunctival hyperemia.⁹

The medication is packaged in an opaque bottle, which may make it harder for the patient to monitor their supply of eye drops.

One advantage of Lumigan is that it is available in 2.5 mL, 5 mL, and 7.5 mL quantities. The newer prostaglandin analogs do not degenerate, so they can be sold in larger bottle sizes.

A patient could potentially obtain a 3-month supply of Lumigan at one time. This option could benefit a patient who has problems obtaining monthly refills.

The original 0.03% formulation has demonstrated large amounts of hyperemia in patients.⁹ Because this discouraged both physicians and patients from using it, a lower strength of Lumigan 0.01% has been developed. The preservative concentration was also changed with a resultant 65% less moderate to severe hyperemia and equivalent clinical efficacy.¹⁰

Tafluprost (Zioptan)

This is the only preservative-free prostaglandin analog available; therefore, it is packaged in individual unit dose vials that are to be used once and then discarded.

There is enough liquid in 1 vial to apply 1 drop to each eye. Any remaining liquid in the vial should be discarded.

Extra vials should be stored in the refrigerator. Once the vials are removed from the refrigerator, they should be used within 28 days.

Individual unit dose packaging appears to be tafluprost’s only difference from the other prostaglandin analog eye drops. The dosing and side effect profile of tafluprost is similar to the other prostaglandin analogs.

Final Thoughts

Prostaglandin analogs are an effective group of eye drops and considered first-line treatment for many types of glaucoma. Because dosing and side effect profiles are similar among the medications, the choice of prostaglandin analog is most dependent upon cost, preservation, and tolerability.^6,11,12

References

1. Xalatan (latanoprost ophthalmic solution) 0.005%. Package insert. 2006

2. Alm A, Stjernschantz J. Effects on intraocular pressure and side effects of 0.005% latanoprost applied once daily, evening or morning: a comparison with timolol. Ophthalmology. 1995;102:1743-1752.

3. Konstas GP, Mikropoulos D, Kaltsos K, et al. 24 hour intraocular pressure control obtained with evening versus morning dosed travoprost in primary open-angle glaucoma. Ophthalmology. 2006;113:446-450.

4. Travatan (travoprost ophthalmic solution) 0.004%. Package insert. 2002.

5. Lumigan (bimatoprost ophthalmic solution) 0.01%. Package insert. 2014.

6. Zioptan (tafluprost ophthalmic solution) 0.0015%. Package insert. 2012.

7. Nordmann JP, Baudouin C, Bron A, et al. Xal-Ease: impact of an ocular hypotensive delivery device on ease of eyedrop administration, patient compliance, and satisfaction. Eur J Opthalmol. 2009;19(6):949-56.

8. Parrish RK, Palmberg P, Sheu WP, et al. A comparison of latanoprost, bimatoprost, and travoprost in patients with elevated intraocular pressure: a 12-week, randomized, masked-evaluator multicenter study. Am J Ophthalmol. 2003;135(5); 688-703.

9. Gandolfi S, Simmons ST, Sturm R, et al. Three-month comparison of bimatoprost and latanoprost in patients with glaucoma and ocular hypertension. Adv Ther. 2001;18(3):110-21.

10. Katz LJ, Cohen JS, Batoosingh AL, et al. Twelve-month, randomized, controlled trial of bimatoprost 0.01%, 0.0125%, and 0.03% in patients with glaucoma or ocular hypertension. Am J Opthalmol. 2010;149(4):661-71.

11. Aihara M. Clinical appraisal of tafluprost in the reduction of elevated intraocular pressure (IOP) in open-angle glaucoma and ocular hypertension. Clin Ophthalmol. 2010;4:163-70.

12. Hamacher, T, Airaksinen J, Saarela V, et al. Efficacy and safety levels of preserved and preservative-free tafluprost are equivalent in patients with glaucoma or ocular hypertension: results from a pharmacodynamics analysis. Acta Opthalmol. 2008;242:14-9.

13. Kahook MY, Noecker RJ. Evaluation of adherence to morning versus evening glaucoma medication dosing regimens. Clin Ophthalmol. 2007;1(1):79-83.

14. Morgan PV, Proniuk S, Blanchard J, et al. Effects of temperature and light on the stability of latanoprost and its clinical relevance. J Glaucoma. 2001:10(5):401-5.