General Information: Latanoprost, an analog of prostaglandin F2alpha, is a prodrug used on-label for the treatment of elevated intraocular pressure (IOP). Studies have shown that latanoprost administered once daily as an ophthalmic solution is as effective as1 or more effective than2 timolol in lowering intraocular pressure in patients with open-angle glaucoma or ocular hypertension. When latanoprost and timolol were used in combination, a complete or almost complete additive effect in reducing intraocular pressure was observed.3 During clinical trials, latanoprost-treated eyes had a gradual change in color. This was reportedly due to an increase in the amount of brown pigment in the iris. Post-marketing studies assessing the risk of iridal pigmentation will be conducted. Final FDA approval was granted on June 5, 1996.
Mechanism of Action: Latanoprost is a selective agonist at a subtype of prostaglandin receptors known as the FP receptor. By acting on the FP receptor, latanoprost increases the outflow of aqueous humor thereby reducing intraocular pressure. According to the manufacturer, studies in both animals and man suggest that increased uveoscleral outflow is the primary mechanism of action.
Pharmacokinetics: Latanoprost is administered topically to the scalp. The active acid of latanoprost is primarily metabolized by the liver to the 1,2-dinor and 1,2,3,4- tetranor metabolites via fatty acid beta-oxidation with an elimination half-life of 17 minutes. The metabolites are mainly eliminated by the kidneys with 88% of an administered dose being recovered in the urine.
Pregnancy: Latanoprost is classified as FDA pregnancy risk category C. Although there are no adequate and well-controlled studies in pregnant women, limited experience in human pregnancy has not resulted in clinically significant risk to the fetus. A minimal amount of drug reaches systemic circulation after ophthalmic administration, suggesting exposure of the drug to the fetus is low.4 According to the manufacturer, latanoprost should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.5
According to the manufacturer, it is not known whether latanoprost or its metabolites are excreted in breast milk. Because systemic plasma concentrations of latanoprost are low and the half-life is short after ophthalmic administration, clinically significant amounts of the drug would not be expected to be excreted in breast-milk.4 To further minimize the amount of drug that reaches the systemic circulation and breast milk, apply pressure over the tear duct by the corner of the eye for 1 minute after ophthalmic administration. According to the manufacturer, caution should be exercised when latanoprost is administered during breast-feeding.5 Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.
The safety and efficacy of latanoprost has not been established in children.
Latanoprost should be used cautiously in patients with renal disease (e.g., renal failure, renal impairment) or hepatic disease. There have been no studies on safe use in these patients.
Adverse Reactions: Ocular adverse reactions (ADRs) associated with latanoprost therapy were reported in 5—15% of treated eyes in a 6-month, multi-center, double-blind, active-controlled study performed by the manufacturer. These ADRs include blurred vision (8%), conjunctival hyperemia (8%), foreign body sensation (13%), iridal discoloration (7%), ocular pruritus (8%) ocular irritation (burning (7%) or stinging (9%)), and punctate corneal keratopathy (10%). Iridal discoloration happens slowly and may not be noticeable for several months to several years. This change is caused by an increase in the amount of brown pigment in the iris due to an increased number of melanosomes in melanocytes. The increase in brown pigment has not been shown to progress further upon discontinuation of treatment, however the resultant color change may be permanent. Latanoprost may gradually change eyelashes and vellus hair; these changes include increased length, thickness, pigmentation, number of lashes or hairs (hypertrichosis), and misdirected growth of lashes. Eyelid skin darkening (eyelid skin hyperpigmentation) has also been reported. Adverse reactions reported in 1—5% of patients include xerophthalmia (3%), lacrimation (4%), ocular pain (3%), eyelid crusting (3%), blepharedema (1%), blepharitis (3%), eyelid discomfort (4%), and photophobia (2%). Corneal edema, corneal erosion, keratitis, herpes keratitis, ocular inflammation (iritis/uveitis), periorbital and lid changes resulting in deepening of the eyelid sulcus, and macular edema (including cystoid macular edema) have been reported during post-marketing experience with latanoprost.5
Asthma or asthma exacerbations (bronchospasm) and dyspnea have been reported during post-marketing experience with latanoprost.5
Infection, including upper respiratory tract infection and cold/flu, was reported in 3% of patients during clinical trials.5
Musculoskeletal pain, joint pain (arthralgia), and back pain have been reported in 1% of patients during latanoprost clinical trials.5
Rash (unspecified) and other allergic skin reactions have been reported at a rate of 1% during latanoprost clinical trials. Toxic epidermal necrolysis has been reported during post-marketing use of latanoprost.5
Dizziness and headache have been reported during post-marketing experience with latanoprost.5
Storage: Store this medication in a refrigerator between 36°F to 46°F (2°C - 8°C). Do not freeze. Protect from light. Keep all medicine out of the reach of children. Throw away any medicine after the beyond use date. Do not flush unused medications or pour down a sink or drain.
- 1. Fristrom B. A 6-month, randomized, double-masked comparison of latanoprost with timolol in patients with open angle glaucoma or ocular hypertension. Acta Ophthalmol Scand 1996;74:140-4
- 2. Mishima HK, et al. A comparison of latanoprost and timolol in primary open-angle glaucoma and ocular hypertension. Arch Ophthal 1996;114:929-32.
- 3. Rulo AH, Greve EL, Hoyng PF. Additive effect of latanoprost, a prostaglandin F2alpha analogue, and timolol in patients with elevated intraocular pressure. Br J Ophthalmol 1994;78:899-902.
- 4. Briggs, Freeman, Yaffee. Latanoprost. Update, Drugs in Pregnancy and Lactation. 2011:24;5-6.
- 5. Xalatan (latanoprost ophthalmic solution) package insert. New York, NY: Pfizer; 2014 Nov