Latanoprost

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Latanoprost quick reference

Latanoprost
Latanoprost general drug information
 Pronunciation la TAN oh prost, la TA noe prost (.wav file)
 Trade Name(s) Xalatan
 How Supplied Xalatan 0.005% ophthalmic solution (50 micrograms/mL)
 Generic Availability No generics available
 Patent Expiry Date March 22, 2011
 Classification Prostaglandin analogue used to reduce elevated intraocular pressure in open angle glaucoma or ocular hypertension
 Schedule Rx
 Pregnancy Category C
 Breast-feeding It is not currently known whether Xalatan (latanoprost) or its metabolites are secreted into human breast milk.

The manufacturer recommends cautious use of Xalatan in nursing women.[1]

Latanoprost chemical information
 IUPAC Name isopropyl-(Z)-7[(1R,2R,3R,5S)3,5-dihydroxy-2-[(3R)-3-hydroxy-5-phenylpentyl]cyclopentyl]-5-heptenoate
 Empirical Formula (C26H40O5)
 Molecular Weight 432.58 g/mol
pharmacokinetic information  |  pharmacogenomic information
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Description

Open angle glaucoma results from changes in aqueous humor, resulting in increased intraocular pressure. To maintain intraocular pressure that is constant, the rate of production of aqueous humor by the ciliary processes must be balanced by an equal rate of aqueous humor outflow. Small fluctuations in the production or outflow of aqueous humor will have a large impact on intraocular pressure. Open angle glaucoma is caused by increased pressure within the eye, either through an increased production of aqueous humor or a decreased outflow of aqueous humor. Untreated glaucoma leads to visual field loss and possibly blindness. Current medical therapy for open angle glaucoma either decreases production of aqueous humor or increases outflow of aqueous humor. Increased intraocular pressures present in glaucoma vary from study to study, but in general an intraocular pressure above 20 mm Hg, up to about 35 mm Hg, is considered medically relevent increased intraocular pressure. Increased intraocular pressure is defined as glaucoma if signs and symptoms of glaucoma are present (visual field loss).

The goal of glaucoma treatment is to prevent progressive optic nerve (cranial nerve II) damage with minimal risk of side effects from topical therapy. A stepped medical approach is generally advised that takes into account the patient's ocular status and comorbid conditions. Bronchospastic diseases such as asthma and chronic obstructive pulmonary disease are relative contraindications to topical beta adrenergic receptor antagonists (beta blockers). Significant systemic absorption from topical beta blockers may occur, resulting in side effects. Cardiac arrhythmias and dysrhythmias, such as bradycardia and heart block, are also relative contraindications to topical beta blockers, for similar reasons. A history of kidney stones, nephrolithiasis, is a contraindication to topical and systemic carbonic anhydrase inhibitors.

Topical prostaglandin analogues have once daily dosing, a low risk and incidence of systemic side effects, and a potent intraocular pressure reducing effect, hence, prostaglandin analogues are usually tried initially for glaucoma treatment. Prostaglandin analogues have mostly replaced beta-blockers as first-line therapy for glaucoma. Postaglandin analogues include: latanoprost (Xalatan), travoprost (Travatan) and bimatoprost (Lumigan).

Latanoprost is an ester prodrug that is rapidly hydrolyzed by corneal esterases into the biologically active form. As a prodrug ester, corneal permeability is enhanced. Prostaglandin analogues lower intraocular pressure by increasing aqueous humor outflow through the uveoscleral outflow pathway.

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Mechanism of Action

Latanoprost is an ester prodrug that is rapidly hydrolyzed by corneal esterases into the biologically active form. As a prodrug ester, corneal permeability is enhanced. Latanoprost is an analogue of prostaglandin F-2 alpha, designated as PGF - 2 alpha. PGF - 2 alpha analogues lower intraocular pressure by increasing aqueous humor outflow through the uveoscleral outflow pathway. The exact mechanism through which prostaglandin analogues increase aqueous humor outflow through the uveoscleral pathway is unclear. Prostaglandin analogues bind to FP receptors. It is hypothesized that FP receptors have an associated coupled G protein, Gq11. Binding stimulates Gq11, which then stimulates the phospholipase C (PLC)-IP3-calcium pathway. The PLC-IP3-Ca++ pathway is present in ciliary muscle cells. This pathway may then reduce ciliary muscle tension and release matrix metalloproteases that degrade extracellular matrix metalloproteins which impede uveoscleral aqueous humor outflow. Both matrix metalloprotease stimulation and ciliary muscle tension reduction increase uveoscleral aqueous humor outflow.[1][2]

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Time Required for Therapeutic Response

  • Initial: Reduction of intraocular pressure begins approximately 3-4 hours after topical administration.[1]
  • Maximum: Reduction of intraocular pressure is maximally achieved 8-12 hours after topical administration.[1]
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Pharmacokinetics

Absorption
Latanoprost is an isopropyl ester prodrug that is hydrolyzed to its biologically active acidic form. The prodrug is rapidly absorbed in the cornea, and hydrolysis of the prodrug to its active form occurs in the cornea. After topical administration, the peak concentration within the aqueous humor is reached within about two hours.[1]

Distribution
The volume of distribution in the plasma is 0.16 L/kg+-0.02 L/kg after intravenous administration. The mean plasma clearance after intravenous administration is 0.40 L/hr+-0.04 L/hr. After administering latanoprost into the eye, the mean ocular clearance is 0.88 L/hr, and the ocular volume of distribution is 0.36 L/kg. The acidic active form of latanoprost can be measured within plasma for only an hour after topical administration, but the active form can be measured within the aqueous humor during the first four hours after topical administration.[1] [3]

Metabolism
Latanoprost is an isopropyl ester prodrug that is rapidly hydrolyzed by corneal esterases to the acidic biologically active form. The small amount of acidic biologically active form that reaches the systemic circulation is hepatically metabolized via fatty acid beta-oxidation to the 1,2-dinor and 1,2,3,4-tetranor metabolites.[1]

Excretion
The elimination of the acidic biologically active form from plasma is rapid, with a half-life of approximately 17 minutes, after both topical and intravenous administration. Systemic clearance of the biologically active form is approximately 7 mL/min/kg. After hepatic metabolism via fatty acid beta-oxidation, the 1,2-dinor and 1,2,3,4-tetranor metabolites are primarily renally eliminated. Approximately 88% of the administered dose is recovered in the urine after topical administration, and the rest is found in the feces. The 1,2-dinor and 1,2,3,4-tetranor metabolites account for approximately 66% of the compounds recovered in the urine. Approximately 98% of the administered dose is recovered in the urine after intravenous administration.[1] [3]


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Special Population Pharmacokinetics

  • Renal insufficiency: Not Applicable.[1]
  • Hepatic insufficiency: Not Applicable.[1]
  • Hemodialysis: Not Applicable.[1]
  • Geriatric: Not Applicable.[1]
  • Pediatric: Not Applicable.[1]
  • Gender: Not Applicable.[1]
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Indications and Dosages

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FDA Approved Indications

Adults: Reduction of elevated intraocular pressure in open-angle glaucoma or in ocular hypertension, where patients with ocular hypertension are intolerant of other intraocular pressure reducing medications or are not responsive to other intraocular pressure reducing medications:

  • Starting dose:
    • One drop in the affected eye(s) once daily in the evening.[1]
  • Maintenance dose:
    • One drop in the affected eye(s) once daily in the evening.[1]
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Dosage Adjustment

Renal insufficiency: Specific guidelines for dose adjustment are lacking. Since latanoprost is topically absorbed, it appears that no dose adjustment is necessary in renal insufficiency. Latanoprost should be cautiously used in patients with renal insufficiency; however, the data for this patient population is lacking.[1]
Hepatic insufficiency: Specific guidelines for dose adjustment are lacking. Since latanoprost is topically absorbed, with very little systemic absorption, it appears that no dose adjustment is necessary in hepatic insufficiency. Latanoprost should be cautiously used in patients with hepatic insufficiency; however, the data for this patient population is lacking.[1]
Hemodialysis: No dose adjustment is necessary.[1]
Geriatric: No overall differences in safety and efficacy have been found between the geriatric population and the younger adult population. No dose adjustment is necessary.[1]
Pediatric: Safety and efficacy in the pediatric population has not been established.[1]
Gender: No dose adjustment is necessary.[1]

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Dosage Limits

  • Adults: One drop in the affected eye(s) once daily in the evening.[1]
  • Elderly: One drop in the affected eye(s) once daily in the evening.[1]
  • Adolescents and children: Safety and efficacy in the pediatric population has not been established.[1]


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Administration

  • Route: ophthalmic
  • Method:
    • Remove contact lenses prior to use.
    • Place one drop in the affected eye(s) once daily in the evening.
    • Wait at least five minutes before applying other medications to the same eye.
    • Contact lenses may be reinserted 15 minutes after administration.[1]
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Monitoring Parameters

  • Funduscopic (eye exam) regularly, at least twice yearly, with visual field testing, a dilated fundus exam, and intraocular pressure measured at each eye exam.[1][4]


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Contraindications/Precautions

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Contraindications

  • History of allergic hypersensitivity to latanoprost, benzalkonium chloride, or any other inactive ingredients in the product.[1]
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Precautions

  • History of intraocular inflammation, i.e. iritis or uveitis.
  • Active intraocular inflammation, ie iritis or uveitis.
  • Risk factors for macular edema or a family history of macular edema.
  • Absence of an intact posterior lens capsule.[1]
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Pregnancy indications

Category C There are no well-controlled adequate studies of latanoprost in pregnant women, but reproductive studies have tested rats and rabbits. In rabbits, a lack of viable fetuses occurred at a dosage that was approximately 80 times the maximum human dose. The highest dose in rabbits that did not kill embryos was approximately 15 times the maximum human dose. Latanoprost should be used in pregnant women only if the potential benefit to the pregnant woman outweighs the potential risk to the foetus.[1]

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Breast-feeding indications

It is not currently known whether latanoprost or its metabolites are secreted into human breast milk.
The manufacturer recommends cautious use in nursing women.[1]

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Drug-Drug, -Food, -Herb Interactions

Click the link above to go to the drug interactions page.

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Adverse Reactions/Side Effects

Latanoprost Adverse Reactions Chart
Incidence Body System Adverse Reactions
>10% All Ocular (all adverse events were only given as >10%): blurred vision, burning, stinging, conjunctival hyperemia (redness), itching, foreign body sensation, increased pigmentation of the iris
1-10% CNS NONE
Cardiovascular chest pain(1-2%), angina pectoris(1-2%)
Dermatologic rash(1-2%), allergic skin reaction (1-2%)
Neuromuscular/skeletal myalgia/muscle pain (1-2%), arthralgia/joint pain (1-2%), back pain(1-2%)
Respiratory upper respiratory tract infection (4%): cold(4%), flu(4%)
Ocular (all ocular adverse events were between 1-4%): dry eye, excessive tearing, eye pain, eyelid crusting, eyelid edema, eyelid erythema (redness), eyelid discomfort/pain, photophobia
<1% All Respiratory: asthma, dyspnea; Dermatologic: toxic epidermal necrolysis; CNS: dizziness, headache; Ocular: conjunctivitis, corneal edema, corneal erosion, diplopia (double vision), discharge from the eye, eyelash changes, eyelid skin darkening, herpes keratitis, iritis, macular edema, retinal artery embolus, retinal detachment, uveitis, vitreous hemorrhaging.
[1][4]
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Overdosage Measures

Besides ocular irritation and conjunctival or episcleral hyperemia, the ocular effects from overdose and high dosages are not currently known. Transient bronchoconstriction has been observed with intravenous administration of large latanoprost doses into monkeys. However, the manufacturer reported that their study of 11 patients with bronchial asthma that were treated with latanoprost had no bronchoconstrictive adverse effects. The manufacturer administered latanoprost at a dose of 3 micrograms/kg through intravenous infusion into healthy volunteers. This high-dose intravenous infusion resulted in mean plasma concentrations of latanoprost that were 200 times higher than during clinical treatment trials, and no adverse effects of high-dose intravenous infusion were observed. However, even higher intravenous infusion doses that were studied by the manufacturer (5.5-10 micrograms/kg) caused abdominal pain, nausea, fatigue, dizziness, hot flushes/flashes, and sweating.[1]


Treatment:

  • Should overdose of latanoprost occur, then treatment should be primarily symptomatic and supportive.[1]


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Product Information and Distribution

Note: appearance only available for brand-name product
50 micrograms/1 mL solution clear - sterile, isotonic, buffered, preserved aqueous ophthalmic solution, pH approximately 6.7, osmolality approximately 267 mOsm/kg, clear and colorless solution; supplied as a 2.5 mL solution in a 5 mL clear polyethylene bottle with a clear polyethylene dropper tip, a turquoise polyethylene screw cap, and a tamper-evident clear polyethylene cap; Xalatan is available as a multi-pack of 3 bottles.
  • Active ingredients for solution: 50 micrograms/1 mL latanoprost solution, 0.02% benzalkonium chloride is a preservative in this formula.[1]
  • Inactive ingredients for solution: sodium chloride, sodium dihydrogen phosphate monohydrate, disodium hydrogen phosphate anhydrous, and water for injection.[1]
  • Storage Conditions: Keep unopened bottle(s) protected from light and under refridgeration at temperatures between 2-8 degrees Celsius (36-46 degrees Fahrenheit). Once a bottle of is opened, protect it from light and keep it at room temperature, up to 25 degrees Celsius (77 degrees Fahrenheit). Opened bottles that are stored at room temperature, up to 25 degrees Celsius (77 degrees Fahrenheit), are stable and effective for up to 6 weeks. Discard opened bottles after 6 weeks.[1]
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Patient Information

  • If you miss a dose of latanoprost, wait until the next dose to administer it as normal.
  • Store unopened bottle(s) in a refrigerator (2-8 degrees C; 36-46 degrees F); protect from light.
  • Store an opened bottle at room temperature (up to 25 degres C; up to 77 degrees F); protect from light.
  • Discard opened bottles after 6 weeks.
  • Do not touch the dropper tip with your fingers, to the eye or eyelid, or to any other surface; the tip of the bottle may become contaminated by bacteria or viruses that may cause eye infections. Serious damage to the eye, loss of vision, and possibly blindness may result from contamination of latanoprost solution.
  • Wait at least five minutes before applying other medications to the same eye.
  • Contact lenses must be removed prior to administration; reinsert 15 minutes after administration.
  • May cause changes in pigmentation of the iris, eyelids, and eyelashes.
  • After discontinuation, pigmentation of the iris is likely to be permanent, but pigmentation of the eyelids and eyelashes may be reversible in some people.
  • Treatment with latanoprost can be continued in individuals with increased iris pigmentation, but these individuals should have their eyes examined by an ophthamalogist at regular intervals.
  • Eyelash changes associated with latanoprost include: increased eyelash length, increased eyelash thickness, increased eyelash pigmentation, an increase in the number of hairs of the eyelashes, and misdirected growth of the eyelashes. Eyelash changes are usually gradual during treatment, and eyelash changes are usually reversible upon discontinuing treatment.
  • If you develop or experience an ocular condition while on latanoprost (eye trauma or infection, surgery, or adverse reactions on the eyelid), then seek the advice of your medical doctor regarding the continuation of treatment.
  • Should you undergo ophthalmic cataract surgery, consult your doctor regarding the continued use of latanoprost after surgery.[1]
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References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 1.19 1.20 1.21 1.22 1.23 1.24 1.25 1.26 1.27 1.28 1.29 1.30 1.31 1.32 1.33 1.34 1.35 1.36 1.37 Xalatan® (latanoprost) package insert. New York City, NY; Pfizer, Inc./Cardinal Health; 2006 November.
  2. ↑ Henderer, Jeffrey D. and Rapuano, Christopher J. Ocular Pharmacology. In: Brunton L, Lazo J, Parker K, eds. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 11th ed. New York, NY: McGraw-Hill; 2006: 1707-1737.
  3. ↑ 3.0 3.1 Sjoquist B, Stjernschantz J. Ocular and systemic pharmacokinetics of latanoprost in humans. Surv. Ophthalmol. 2002;47(supplement 1):S6-S12.
  4. ↑ 4.0 4.1 Semla T, Beizer J, Higbee M. Geriatric Dosage Handbook. Hudson, Ohio: American Pharmacists Association (Lexi-Comp); 2007: 858-859.
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PUBMED References

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Efficacy Trial Articles

  1. Haverkamp F, Wuensch S, Fuchs M, Stewart WC. Intraocular pressure, safety and quality of life in glaucoma patients switching to latanoprost from adjunctive and monotherapy treatments. Eur. J. Ophthalmol. 2004;14(5):407-415.
  2. Bayer A, Weiler W, Oeverhaus U, Skrotzki FE, Stewart WC. Two year follow up of latanoprost 0.005% monotherapy after changing from previous glaucoma therapies. J. Ocul. Pharmacol. Ther. 2004;20(6):470-478.
  3. Kurtz S, Shemesh G. The efficacy and safety of once daily versus once weekly latanoprost treatment for increased intraocular pressure. J. Ocul. Pharmacol. Ther. 2004;20(4):321-327.
  4. Rossetti L, Gandolfi S, Traverso C, Montanari P, Uva M, Manni G, Carassa R, Mastropasqua L, Quaranta L, Marchini G, Ratiglia R, Orzalesi N. An evaluation of the rate of nonresponders to latanoprost therapy. Journal of Glaucoma. 2006;15(3):238-243.
  5. Oh JY, Park KH. The effect of latanoprost on intraocular pressure during 12 months of treatment for normal tension glaucoma. Korean J. Ophthalmol. 2005;19(4):297-301.
  6. Bayer A, Henderer JD, Kwak T, Myers J, Fontanarosa J, Spaeth GL. Clinical predictors of latanoprost treatment effect. Journal of Glaucoma. 2005;14(4):260-263.
  7. Thomas R, Parikh R, Sood D, Vijaya L, Sekhar GC, Sood NN, Baskaran M, Prasad KK. Efficacy and safety of latanoprost for glaucoma treatment: a three month multicentric study in India. Indian J. Ophthalmol. 2005;53(1):23-30.
  8. Smith SL, Sine CS, Pruitt CA, Stewart WC. The use of latanoprost 0.005% once daily and its effect on intraocular pressure as primary or adjunctive therapy. J. Ocul. Pharmacol. Ther. 1999;15(1):29-39.
  9. Camras CB, Wax MB, Ritch R, Weinreb R, Robin AL, Higginbotham EJ, Lustgarten J, Stewart WC, Sherwood M, Krupin T, Wilensky J, Cioffi GA, Katz LJ, Schumer RA, Kaufman PL, Minckler D, Zimmerman T, Stjernschantz J. Latanoprost treatment for glaucoma: effects of treating for 1 year and of switching from timolol. United States Latanoprost Study Group. Am. J. Ophthalmol. 1998;126(3):390-399.
  10. Watson PG. Latanoprost. Two years' experience of its use in the United Kingdom. Latanoprost Study Group. Ophthalmology. 1998;105(1):82-87.
  11. Camras CB, Alm A, Watson P, Stjernschantz J. Latanoprost, a prostaglandin analog, for glaucoma therapy. Efficacy and safety after 1 year of treatment in 198 patients. Ophthalmology. 1996;103(11):1916-1924.
  12. Camras CB. Comparison of latanoprost and timolol in patients with ocular hypertension and glaucoma: a six month masked, multicenter trial in the United States. The United States Latanoprost Study Group. Ophthalmology. 1996;103(1):138-147.
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Therapeutic Class Comparison Articles

  1. Hedman K, Alm A, Gross RL. Pooled data analysis of three randomized, double masked, six month studies comparing intraocular pressure reducing effects of latanoprost and timolol in patients with ocular hypertension. Journal of Glaucoma. 2003;12(6):463-465.
  2. Konstas AG, Kozobolis VP, Katsimpris IE, Boboridis K, Koukoula S, Jenkins JN, Stewart WC. Efficacy and safety of latanoprost versus travoprost in exfoliative glaucoma patients. Ophthalmology. 2007;114(4):653-657.
  3. Mundorf T, Noecker RJ, Earl M. Ocular hypotensive efficacy of brimonidine 0.15% as adjunctive therapy with latanoprost 0.005% in patients with open-angle glaucoma or ocular hypertension. Advances in Therapy. 2007;24(2):302-309.
  4. Camras CB, Sheu WP. Latanoprost or brimonidine as treatment for elevated intraocular pressure: multicenter trial in the United States. Journal of Glaucoma. 2005;14(2):161-167.
  5. Konstas AG, Mylopoulos N, Karabatsas CH, Kozobolis VP, Diafas S, Papapanos P, Georgiadis N, Stewart WC. Diurnal intraocular pressure reduction with latanoprost 0.005% compared to timolol maleate 0.5% as monotherapy in subjects with exfoliation glaucoma. Eye. 2004;18(9):893-899.
  6. Kitnarong N, Zhao Y, Netland PA, Kent AR. Efficacy of latanoprost and timolol maleate in black and white patients. Advances in Therapy. 2004;21(4):203-213.
  7. Holmstrom S, Buchholz P, Walt J, Wickstrøm J, Aagren M. Analytic review of bimatoprost, latanoprost and travoprost in primary open angle glaucoma. Curr. Med. Res. Opin. 2005;21(11):1875-1883.
  8. Ishida N, Odani-Kawabata N, Shimazaki A, Hara H. Prostanoids in the therapy of glaucoma. Cardiovascular drug reviews. 2006;24(1):1-10.
  9. Zimmerman TJ, Stewart WC. Intraocular pressure, safety, and quality of life in glaucoma patients switching to latanoprost from monotherapy treatments. J. Ocul. Pharmacol. Ther. 2003;19(5):405-415.
  10. Rossetti L, Karabatsas CH, Topouzis F, Vetrugno M, Centofanti M, Boehm A, Viswanathan A, Vorwerk C, Goldblum D. Comparison of the Effects of Bimatoprost and a Fixed Combination of Latanoprost and Timolol on Circadian Intraocular Pressure. Ophthalmology. 2007 Apr 23; [Epub ahead of print
  11. Topouzis F, Melamed S, Danesh-Meyer H, Wells AP, Kozobolis V, Wieland H, Andrew R, Wells D. A 1 year study to compare the efficacy and safety of once daily travoprost 0.004%/timolol 0.5% to once daily latanoprost 0.005%/timolol 0.5% in patients with open angle glaucoma or ocular hypertension. Eur. J. Ophthalmol. 2007;17(2):183-190.
  12. Harasymowycz P, Hutnik CM, Nicolela M, Stewart WC. Latanoprost versus timolol gel forming solution once daily in primary open angle glaucoma or ocular hypertension. Can. J. Ophthalmol. 2007;42(1):75-81.
  13. Denis P, Lafuma A, Khoshnood B, Mimaud V, Berdeaux G. A meta analysis of topical prostaglandin analogues intraocular pressure lowering in glaucoma therapy. Curr. Med. Res. Opin. 2007;23(3):601-608.
  14. Garcia Feijoo J, Martinez de la Casa JM, Castillo A, Mendez C, Fernandez Vidal A, Garcia Sanchez J. Circadian IOP lowering efficacy of travoprost 0.004% ophthalmic solution compared to latanoprost 0.005%. Curr. Med. Res. Opin. 2006;22(9):1689-1697.
  15. Fung AT, Reid SE, Jones MP, Healey PR, McCluskey PJ, Craig JC. Meta analysis of randomised controlled trials comparing latanoprost with brimonidine in the treatment of open angle glaucoma, ocular hypertension or normal tension glaucoma. Br. J. Ophthalmol. 2007;91(1):62-68.
  16. Dirks MS, Noecker RJ, Earl M, Roh S, Silverstein SM, Williams RD. A 3 month clinical trial comparing the IOP lowering efficacy of bimatoprost and latanoprost in patients with normal tension glaucoma. Advances in therapy. 2006;23(3):385-394.
  17. Parmaksiz S, Yuksel N, Karabas VL, Ozkan B, Demirci G, Caglar Y. A comparison of travoprost, latanoprost, and the fixed combination of dorzolamide and timolol in patients with pseudoexfoliation glaucoma. Eur. J. Ophthalmol. 2006;16(1):73-80.
  18. Magacho L, Reis R, Shetty RK, Santos LC, Avila MP. Efficacy of latanoprost or fixed combination latanoprost timolol in patients switched from a combination of timolol and a nonprostaglandin medication. Ophthalmology. 2006;113(3):442-445.
  19. Law SK, Song BJ, Fang E, Caprioli J. Feasibility and efficacy of a mass switch from latanoprost to bimatoprost in glaucoma patients in a prepaid Health Maintenance Organization. Ophthalmology. 2005;112(12):2123-2130.
  20. Fechtner RD, McCarroll KA, Lines CR, Adamsons IA. Efficacy of the dorzolamide timolol fixed combination versus latanoprost in the treatment of ocular hypertension or glaucoma: combined analysis of pooled data from two large randomized observer and patient-masked studies. J. Ocul. Pharmacol. Ther. 2005;21(3):242-249.
  21. Susanna R Jr, Medeiros FA, Vessani RM, Giampani J Jr, Borges AS, Jordao ML. Intraocular pressure fluctuations in response to the water drinking provocative test in patients using latanoprost versus unoprostone. J. Ocul. Pharmacol. Ther. 2004;20(5):401-410.
  22. Simmons ST, Dirks MS, Noecker RJ. Bimatoprost versus latanoprost in lowering intraocular pressure in glaucoma and ocular hypertension: results from parallel group comparison trials. Advances in Therapy. 2004;21(4):247-262.
  23. Susanna R Jr, Sheu WP. Comparison of latanoprost with fixed combination dorzolamide and timolol in adult patients with elevated intraocular pressure: an eight week, randomized, open label, parallel group, multicenter study in Latin America. Clinical Therapeutics. 2004;26(5):755-768.
  24. Walters TR, DuBiner HB, Carpenter SP, Khan B, VanDenburgh AM. 24 hour IOP control with once daily bimatoprost, timolol gel forming solution, or latanoprost: a 1 month, randomized, comparative clinical trial. Surv. Ophthalmol. 2004;49(Supplement 1):S26-S35.
  25. Choplin N, Bernstein P, Batoosingh AL, Whitcup SM. A randomized, investigator masked comparison of diurnal responder rates with bimatoprost and latanoprost in the lowering of intraocular pressure. Surv. Ophthalmol. 2004;49(Supplement 1):S19-S25.
  26. Dubiner HB, Sircy MD, Landry T, Bergamini MV, Silver LH, Darell Turner F, Robertson S, Andrew RM, Weiner A, Przydryga J. Comparison of the diurnal ocular hypotensive efficacy of travoprost and latanoprost over a 44 hour period in patients with elevated intraocular pressure. Clinical Therapeutics. 2004;26(1):84-91.
  27. Fechtner RD, Airaksinen PJ, Getson AJ, Lines CR, Adamsons IA. Efficacy and tolerability of the dorzolamide 2% timolol 0.5% combination (Cosopt) versus 0.005% Xalatan in the treatment of ocular hypertension or glaucoma: results from two randomized clinical trials. Acta Ophthalmol. Scand. 2004;82(1):42-48.
  28. Diestelhorst M, Larsson LI. A 12 week study comparing the fixed combination of latanoprost and timolol with the concomitant use of the individual components in patients with open angle glaucoma and ocular hypertension. Br. J. Ophthalmol. 2004;88(2):199-203.
  29. Pillunat LE, Larsson LI. Intraocular pressure after replacement of current dual therapy with latanoprost monotherapy in patients with open angle glaucoma. Br. J. Ophthalmol. 2003;87(12):1492-1496.
  30. Sihota R, Saxena R, Agarwal HC, Pandey RM, Gulati V. Peak pressures: crossover study of timolol and latanoprost. Eur. J. Ophthalmol. 2003;13(6):546-552.
  31. Noecker RS, Dirks MS, Choplin NT, Bernstein P, Batoosingh AL, Whitcup SM. A six month randomized clinical trial comparing the intraocular pressure lowering efficacy of bimatoprost and latanoprost in patients with ocular hypertension or glaucoma. Am. J. Ophthalmol. 2003;135(1):55-63.
  32. Bayer A, Tas A, Sobaci G, Henderer JD. Efficacy of latanoprost additive therapy on uncontrolled glaucoma. Ophthalmologica. 2002;216(6):443-448.
  33. Konstas AG, Kozobolis VP, Tersis I, Leech J, Stewart WC. The efficacy and safety of the timolol/dorzolamide fixed combination vs latanoprost in exfoliation glaucoma. Eye. 2003;17(1):41-46.
  34. Gandolfi SA, Cimino L. Effect of bimatoprost on patients with primary open angle glaucoma or ocular hypertension who are nonresponders to latanoprost. Ophthalmology. 2003;110(3):609-614.
  35. Costagliola C, Del Prete A, Verolino M, Antinozzi P, Fusco R, Parmeggiani F, Mastropasqua L. Effect of 0.005% latanoprost once daily on intraocular pressure in glaucomatous patients not adequately controlled by beta blockers twice daily: a 3 year follow up. Experience and incidence of side effects in a prospective study on 76 patients. Graefes Arch. Clin. Exp. Ophthalmol. 2002;240(5):379-386.
  36. Zhang WY, Po AL, Dua HS, Azuara-Blanco A. Meta analysis of randomised controlled trials comparing latanoprost with timolol in the treatment of patients with open angle glaucoma or ocular hypertension. Br. J. Ophthalmol. 2001;85(8):983-990.
  37. DuBiner H, Cooke D, Dirks M, Stewart WC, VanDenburgh AM, Felix C. Efficacy and safety of bimatoprost in patients with elevated intraocular pressure: a 30 day comparison with latanoprost. Surv. Ophthalmol. 2001;45(Supplement 4):S353-S360.
  38. Bron AM, Denis P, Nordmann JP, Rouland JF, Sellem E, Johansson M. Additive IOP reducing effect of latanoprost in patients insufficiently controlled on timolol. Acta Ophthalmol. Scand. 2001;79(3):289-293.
  39. Stewart WC, Day DG, Stewart JA, Schuhr J, Latham KE. The efficacy and safety of latanoprost 0.005% once daily versus brimonidine 0.2% twice daily in open angle glaucoma or ocular hypertension. Am. J. Ophthalmol. 2001;131(5):631-635.
  40. Einarson TR, Kulin NA, Tingey D, Iskedjian M. Meta analysis of the effect of latanoprost and brimonidine on intraocular pressure in the treatment of glaucoma. Clinical Therapeutics. 2000;22(12):1502-1515.
  41. Stewart WC, Day DG, Stewart JA, Holmes KT, Leech JN, Rowan CT, Schwartz GF. Therapeutic success of latanoprost 0.005% compared to brimonidine 0.2% in patients with open-angle glaucoma or ocular hypertension. J. Ocul. Pharmacol. Ther. 2000;16(6):557-564.
  42. Garcia Sanchez J. Efficacy and side effects of latanoprost monotherapy compared to adding dorzolamide to timolol in patients with glaucoma and ocular hypertension: a three month randomised study. Spanish Latanoprost Study Group. Eur. J. Ophthalmol. 2000;10(3):198-204.
  43. Stewart WC, Sharpe ED, Day DG, Kolker AE, Konstas AG, Lee WH, Rieser JC, Chopra H, Holmes KT. Comparison of the efficacy and safety of latanoprost 0.005% compared to brimonidine 0.2% or dorzolamide 2% when added to a topical beta adrenergic blocker in patients with primary open angle glaucoma or ocular hypertension. J. Ocul. Pharmacol. Ther. 2000;16(3):251-259.
  44. O'Donoghue EP. A comparison of latanoprost and dorzolamide in patients with glaucoma and ocular hypertension: a 3 month, randomised study. Ireland Latanoprost Study Group. Br. J. Ophthalmol. 2000;84(6):579-582.
  45. Mastropasqua L, Carpineto P, Ciancaglini M, Gallenga PE. A 12 month, randomized, double masked study comparing latanoprost with timolol in pigmentary glaucoma. Ophthalmology. 1999;106(3):550-555.
  46. 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(12):1743-1752.
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Pharmacokinetics Articles

  1. Sjoquist B, Stjernschantz J. Ocular and systemic pharmacokinetics of latanoprost in humans. Surv. Ophthalmol. 2002;47(supplement 1):S6-S12.
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Drug Interaction Articles

  1. Kent AR, Vroman DT, Thomas TJ, Hebert RL, Crosson CE. Interaction of pilocarpine with latanoprost in patients with glaucoma and ocular hypertension. Journal of Glaucoma. 1999;8(4):257-262.
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Adverse Effects Articles

  1. Alm A, Schoenfelder J, McDermott J. A 5 year, multicenter, open label, safety study of adjunctive latanoprost therapy for glaucoma. Arch. Ophthalmol. 2004;122(7):957-965.
  2. Parrish RK, Palmberg P, Sheu WP. 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.


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Compliance Articles

  1. Wilensky J, Fiscella RG, Carlson AM, Morris LS, Walt J. Measurement of persistence and adherence to regimens of IOP lowering glaucoma medications using pharmacy claims data. Am. J. Ophthalmol. 2006;141(supplement 1):S28-S33.
  2. Rouland JF, Le Pen C, Benhaddi H, Piriou E, Lilliu H, Kenigsberg PA. Naturalistic, prospective study of glaucoma and ocular hypertension treatment in France: Strategies, clinical outcomes, and costs at 2 years. Eur. J. Ophthalmol. 2005;15(5):562-580.
  3. Day DG, Schacknow PN, Sharpe ED, Ellyn JC, Kulze JC 3rd, Threlkeld AB, Jones ED, Brown RH, Jenkins JN, Stewart WC. A persistency and economic analysis of latanoprost, bimatoprost, or beta blockers in patients with open angle glaucoma or ocular hypertension. J. Ocul. Pharmacol. Ther. 2004;20(5):383-392.
  4. Schwartz GF, Reardon G, Mozaffari E. Persistency with latanoprost or timolol in primary open angle glaucoma suspects. Am. J. Ophthalmol. 2004;137(supplement 1):S13-S16.
  5. Reardon G, Schwartz GF, Mozaffari E. Patient persistency with topical ocular hypotensive therapy in a managed care population. Am. J. Ophthalmol. 2004;137(supplement 1):S3-S12.
  6. Zimmerman TJ, Stewart WC. Intraocular pressure, safety, and quality of life in glaucoma patients switching to latanoprost from monotherapy treatments. J. Ocul. Pharmacol. Ther. 2003;19(5):405-415.
  7. Reardon G, Schwartz GF, Mozaffari E. Patient persistency with pharmacotherapy in the management of glaucoma. Eur. J. Ophthalmol. 2003;13(supplement 4):S44-S52.
  8. Reardon G, Schwartz GF, Mozaffari E. Patient persistency with ocular prostaglandin therapy: a population based, retrospective study. Clinical Therapeutics. 2003;25(4):1172-1185.
  9. Shaya FT, Mullins CD, Wong W, Cho J. Discontinuation rates of topical glaucoma medications in a managed care population. Am. J. Manag. Care. 2002;8(supplement 10):S271-S277.
  10. Spooner JJ, Bullano MF, Ikeda LI, Cockerham TR, Waugh WJ, Johnson T, Mozaffari E. Rates of discontinuation and change of glaucoma therapy in a managed care setting. Am. J. Manag. Care. 2002;8(supplement 10):S262-S270.
  11. Dasgupta S, Oates V, Bookhart BK, Vaziri B, Schwartz GF, Mozaffari E. Population based persistency rates for topical glaucoma medications measured with pharmacy claims data. Am. J. Manag. Care. 2002;8(supplement 10):S255-S261.


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Pharmacoeconomic Articles

  1. Goldberg LD, Walt J. Cost considerations in the medical management of glaucoma in the US: estimated yearly costs and cost effectiveness of bimatoprost compared with other medications. Pharmacoeconomics. 2006;24(3):251-264.
  2. Fiscella R, Walt J. Estimated comparative costs of achieving a 20% reduction in intraocular pressure with bimatoprost or latanoprost in patients with glaucoma or ocular hypertension. Drugs & Aging. 2006;23(1):39-47.
  3. Noecker RJ, Walt JG. Cost effectiveness of monotherapy treatment of glaucoma and ocular hypertension with the lipid class of medications. Am. J. Ophthalmol. 2006;141(Supplement 1):S15-S21.
  4. Costagliola C, Parmeggiani F, Sebastiani A. Assessing the cost effectiveness of switching from a beta blocker to latanoprost in the treatment of ocular hypertension. Expert Opinion on Pharmacotherapy. 2003;4(10):1775-1788.
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External Links

Clinical treatment guidelines

  • [http://www.aoa.org/documents/CPG-9.pdf American Optometric Association. Care of the patient with open angle glaucoma. 2nd ed. St. Louis (MO): American Optometric Association. 2002;Aug 17:1-72.

Patient information pages

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